FEMALE REPRODUCTIVE PHYSIOLOGY

2021
DR. MASIKA
 FEMALE REPRODUCTIVE ORGANS

• Female reproductive system comprises of primary sex organs

and accessory sex organs
• PRIMARY SEX ORGANS
Primary sex organs are a pair of ovaries, which produce eggs
or ova and secrete female sex hormones, the estrogen and
progesterone.
• ACCESSORY SEX ORGANS
Accessory sex organs in females are:
1. A system of genital ducts: Fallopian tubes, uterus, cervix
and vagina.
• 2. External genitalia: Labia majora, labia minora and clitoris.
Mammary glands are not the female genital organs, but are
the important glands of female reproductive system.
 FUNCTIONAL ANATOMY OF ACCESSORY SEX ORGANS

• Uterus
Uterus is otherwise known as womb. It lies in the pelvic cavity,
in between the rectum and urinary bladder.
• is a hollow muscular organ with a thick wall. It has a central
cavity, which opens into vagina through cervix. On either side at
its upper part, the fallopian tubes open.
• communicates with peritoneal cavity through fallopian tubes.
Virgin uterus is pyriform in shape and is flattened antero-
posteriorly. It measures about 7.5 cm in length, 5 cm in breadth
at its upper part and about 2.5 cm in thickness.
• There is a constriction almost at the middle of uterus called
isthmus.
 Divisions of uterus

• Uterus is divided into three portions:

1. Fundus (above the entrance points of fallopian
tubes)
2. Body (between fundus and isthmus)
3. Cervix (below isthmus).

• Uterus is made up of three layers:

1. Serous or outer layer
2. Myometrium or middle muscular layer
3. Endometrium or inner mucus layer.
 Structure of uterus cont’

• 1. Serous or outer layer: Serous or outer layer is the covering of

uterus derived from peritoneum. Anteriorly, it covers the uterus
completely, but posteriorly it covers only up to the isthmus.
2. Myometrium or middle muscular layer: Myometrium is the
thickest layer of uterus and it is
made up of smooth muscle fibers. Smooth muscle fibers of
myometrium are arranged in three layers:
i. External myometrium with transversely arranged muscle fibers
• ii. Middle myometrium with muscle fibers arranged
longitudinally, obliquely and transversely
iii. Internal myometrium with circular muscle fibers. Muscular
layer is interdisposed with blood vessels, fibers, lymphatic
vessels and areolar tissues.
• is smooth and soft with pale red color. It is made up of ciliated
3. Endometrium or inner mucus layer

columnar epithelial cells. Surface of the endometrium has

minute orifices, through which tubular follicles of endometrium
open.
• contains connective tissue in which the uterine glands are
present. Uterine glands are lined by ciliated columnar epithelial
cells.
• Epithelial lining is made up of columnar cells. Before menarche
(i.e. the age of onset of menstruation) the cells are ciliated, but
thereafter most of the cells may not have cilia.
• Stroma of the endometrium is highly cellular and contains
numerous blood vessels and numerous simple tubular uterine
glands, which are lined by the columnar epithelium.
 Functional divisions of endometrium
1. Stratum functionale includes the superficial two-thirds
thickness of endometrium, which undergoes monthly
cyclic changes in preparation for the implantation of
fertilized ovum and is shed during menstruation. This
portion of endometrium is supplied by long and spiral
(coiled) arteries.
2. Stratum basale is the deeper one-third layer of
endometrium. It does not participate in the cyclic
changes but functions as a regenerative layer. This part
of endometrium is supplied by short and straight basal
arteries.
 Changes in uterus

• changes its size, structure and function in different phases

of sexual life.
• Just before menstruation, it is enlarged, becomes more
vascular.
• The endometrium thickens with more blood supply. This
layer is desquamated during menstruation and reformed
after menstrual period.
• During pregnancy, uterus is enlarged very much with
increase in weight.
• After parturition (delivery), it comes back to its original size
but the cavity remains larger.
• In old age, uterus is atrophied.
• Cervix is the lower constricted part of uterus. It is
Ce rvi x

divided into two portions:

1. Upper supravaginal portion, which communicates
with body of uterus through internal os (orifice) of
cervix. Mucus membrane of this portion has
glandular follicles, which secrete mucus.
2. Lower vaginal portion, which projects into the
anterior wall of the vagina and it communicates
with vagina through external os (orifice) of cervix.
Mucus membrane of this portion is formed by
stratified epithelial cells.
1. Perimetrium is the outermost serous layer.
St ructu reof cerv ix

2. Myometrium layer of the cervix is much less muscular as compared

to the body of uterus and contains more connective tissue. During
child birth, when the myometrium of body of uterus contracts, the
myometrium of cervix dilates, consequently the cervical canal
becomes large enough for the fetal head to pass through.
3. Endocervix refers to the innermost mucosal layer of cervix in contrast
to the endometrium of the body of uterus; not shed at the time of
menstruation. Endocervix consists of:
• Epithelium. The mucous membrane of the upper 2/3 of cervical canal
is lined by ciliated columnar epithelium, but its lower 1/3 epithelium
is non-ciliated columnar. Near the external os, the canal is lined by
stratified squamous epithelium.
• Stroma. The stroma of the cervix is less cellular than that of the body
of uterus.
 Fallopian tubes
• Each fallopian tube (uterine tube) is approx 10 cm in length
and 8 mm in diameter. It has a medial or uterine end which is
attached to and opens into the uterus and a lateral end opens
into the peritoneal cavity near the ovary.
• Parts. Each fallopian tube can be divided into four parts :
1. Uterine or interstitial part is the most medial part which
passes through the thick uterine wall.
2. Isthmus is the relatively narrow and thick-walled part which is
just next to the uterine part. It is about 2.5 cm in length.
3. Ampulla is the next thin walled and dilated part. It is the
largest part (7 cm) of uterine tube.
 Fallopian tubes cont’
• 4. Infundibulum refers to the funnel-shaped lateral end of the tube.
It is prolonged into a number of finger-like processes known as
fimbria. One fimbria is longer than rest of the fimbriae and is
attached to the outer pole of ovary.
• Structure: consist of same three coats as of the uterus viz.
endometrium, myometrium and perimetrium.
• Functions: convey ova, shed by the ovaries, to the uterus. Ova enter
the tube at its fimbriated end. The sperms enter the uterine tube at
its medial end after traversing the vagina and uterine cavity.
Secretions present in the tubes provide nutrition, oxygen and other
requirements for ova and spermatozoa passing through the tube.
• Fertilization takes place in the ampulla and the fertilized ovum travels
towards the uterus through the tube.
• The ciliated epithelial cells lining the tube help to move ova towards
the uterus.
 Va gi na

• is a musculomembranous tube (about 8–10 cm long) located anterior

to the rectum and posterior to the urethra and urinary bladder.
• Its upper end surrounds the lower part of the cervix and its lower end
i.e. vaginal orifice opens into the vestibule of vagina (the cleft
between the labia minora).
• Structure: wall consists of a mucous membrane, a muscle coat and
an outer fibrous coat or adventitia.
1. Mucous membrane shows numerous longitudinal folds. In adult
female, the vaginal mucosa lined by stratified squamous epithelium.
The epithelial cells are rich in glycogen and this property is oestrogen
dependent.
2. Muscle coat is made up of an outer layer of longitudinal fibres and a
much thinner layer of circular fibres. Many elastic fibres are present
among the muscle fibres. The lower end of vagina is surrounded by
striated fibres of the bulbospongiosus muscle that form a sphincter
for it.
 Va gi na

3. Adventitial coat surrounds the muscle coat and is made up of

fibrous tissue containing many elastic fibres.
• Functions:
i. It serves as the excretory duct for menstrual fluid,
ii. It forms the inferior part of pelvic (birth) canal,
iii. It receives the penis and ejaculate during sexual intercourse.
• Note. No glands open into the vagina. The small amount of
secretion present in the vagina is derived partly from the
mucous discharge from the cervix and partly from the
transudation of fluid from the vaginal epithelium, which
contains glycogen.
• Note. Action of bacteria on the glycogen present in the vaginal
secretion produces lactic acid, which maintains the vaginal pH
around 4.5. Acidic environment of vagina prevents the growth
of pathogenic organisms.
• include mons pubis, labia majora, labia minora, clitoris,
FEM AL EEXTE RNAL GENI T ALI A

vestibule of vagina, bulbs of vestibule and greater vestibular

glands.
• Clitoris is an erectile organ located where the labia minora
meet anteriorly. The clitoris is analogous to male penis. It
functions solely as an organ of sexual arousal.
• Vestibule is the space between the labia minora that contains
the opening of urethra, vagina, and ducts of greater and lesser
vestibular glands. The vaginal orifice is surrounded by a thin
fold of mucous membrane called hymen which is usually
ruptured after first intercourse or otherwise. After child birth,
only a few remnants of the hymen—hymenal caruncles (tags)
—are visible.
• The synonymous terms vulva and pudendum include all these
parts.
 The vulva serves:

i. As sensory and erectile tissue for sexual arousal and

intercourse
ii. To direct the flow of urine
iii. To prevent entry of foreign material into the
urogenital tract
 SEXUAL LIFE IN FEMALES
• Lifespan of a female is divided into three periods.
FIRST PERIOD: extends from birth to puberty. During this
period, primary and accessory sex organs do not function.
These organs remain quiescent. Puberty occurs at the age
of 12 to 15 years.
SECOND PERIOD: extends from onset of puberty to the
onset of menopause. First menstrual cycle is known as
menarche. Permanent stoppage of the menstrual cycle in
old age is called menopause, which occurs at the age of
about 45 to 50 years. During the period between menarche
and menopause, women menstruate and reproduce.
THIRD PERIOD: extends after menopause to the rest of the
life.
 OVARIES
• A pair of ovaries is located (one on each side) behind and
below the fallopian tubes. The ovaries are ovoid glands
with a combined weight of 10–20 g during reproductive
years, which decreases with an increasing age. Each ovary is
about 3–5 cm in length and is attached to the uterus by the
broad ligament and round ligament of ovary.
• Structure: Histologically, each ovary consists of following
parts:
1. Germinal epithelium: refers to the epithelium lining the
outer surface of ovary and consists of a single layer of
cuboidal cells. The term germinal epithelium is a misnomer,
as it does not produce germ cells.
 OVARIES
2. Cortex: is the outer thick main part of the substance of the
ovary. It consists of following tissues:
• Tunica albuginea is the outer condensation of the connective
tissue present immediately below the germinal epithelium.
• Stroma of the cortex, present deep to the tunica albuginea, is
made up of reticular fibres and numerous fusiform cells that
resemble mesenchymal cells.
• Ovarian follicles at various stages of development are scattered
in the stroma. Each follicle contains a developing ovum.
3. Medulla: is the inner small part of the substance of ovary. It
consists of connective tissue in which numerous blood vessels
(mostly veins), smooth muscles and elastic fibres are present.
4. Hilum: refers to the area where ovary attaches to mesentery. It
is the site for entry of blood vessels and lymphatics.
 OVARY
Location : near kidneys, anchored by fallopian tubes
to uterus.
Development: intermediate mesoderm. Ovaries
migrate somewhat caudally, retain position near
kidneys.
Innervation: sympathetic – similar to hindgut, level
T12, follows least splanchnic nerve; parasympathetic –
sacral outflow
Arterial Supply: ovarian artery, branch of abdominal
aorta.
Venous Drainage: ovarian vein, dump into inferior
vena cava.
 OVARY
Function: ovaries produce ova (eggs; singular ovum)
in regular cycle determined by hormonal secretions
(covered in later lectures). Functions of ovarian
hormones and their secretions are tied to secretion of
FSH and LH from anterior pituitary gland.

ESTROGENS – stimulate development of female sex

organs and sexual characteristics.
PROGESTERONE + ESTROGENS – regulate menstrual
cycle; maintain pregnancy in presence of developing
embryo or fetus.
 Ovarian Follicles

• In the intrauterine life, outer part of cortex contains

the germinal epithelium, which is derived from the
germinal ridges. When fetus develops, the germinal
epithelium gives rise to a number of primordial ova.
• The primordial ova move towards the inner
substance of cortex.
• A layer of spindle cells called granulose cells from
the ovarian stroma surround the ova.
• Primordial ovum along with granulosa cells is called
the primordial follicle.
• At 7th or 8th month of intrauterine life, about 6
million primordial follicles are found in the ovary.
 Ovarian Follicles cont’

• But at the time of birth, only 1 million primordial follicles are

seen in both the ovaries and the rest of the follicles degenerate.
• At the time of puberty, the number decreases further to about
300,000 to 400,000. After menarche, during every menstrual
cycle, one of the follicles matures and releases its ovum.
• During every menstrual cycle, only one ovum is released from
any one of the ovaries. During every cycle, many of the follicles
degenerate. The degeneration of the follicles is called atresia
and the degenerated follicles are known as atretic follicles.
• The atretic follicles become fibrous and the fibrotic follicles are
called the corpus fibrosa. Atresia occurs at all levels of follicles.
Usually, the degenerated follicles disappear without leaving any
scar.
 Functions of Ovaries

• Ovaries are the primary sex organs in females.

Functions of ovaries are:
1. Secretion of female sex hormones
2. Oogenesis
3. Menstrual cycle.
 OOGENESIS

• refers to the process of formation of ova from the

primitive germ cells.
• Primitive germ cells. When the bipotential gonads
differentiate into ovaries in genetic female (44 +XX)
embryo by 10th week of gestation, the primitive
germ cells increase in number by mitosis to form
oogonia.
• Oogonia are the stem cells from which ova are
derived. The oogonia proliferate by mitosis to form
primary oocytes.
 Prim ordial follicles

• The diploid primary oocytes become enveloped by a single

layer of flat granulosa cells and in this form are called
primordial follicles.
• After puberty, the oogenesis or formation of ovum occurs
in a highly cyclic fashion, once every 28 days till
menopause.
• Every month, in each ovary, more than one primordial
follicles start undergoing maturation process but only one
reaches maturity and the rest undergo atresia at different
stages of development.
• Thus throughout the whole normal reproductive life of
about 30 years (from 13–42 years) about 450 ova are
expelled and the remainder degenerate.
 Phases of folliculogenesis

1. Primordial follicles are the fundamental reproductive units

of ovary. At the time of puberty, both ovaries contain about
300,000 primordial follicles.
• are formed in fetal life and each consists of the primary
oocyte in prophase of the first meiotic division surrounded
by a single layer of spindle-shaped (flat) cells called the
granulosa cells.
• Both the granulosa cells and the primary oocyte are
enveloped in a thin membrane called basal lamina
• The granulosa provide nutrition to the ovum and also
secrete oocyte maturation inhibiting factor, which keeps
the ovum in immature stage till puberty.
 2. Primary follicle
• is formed when the primordial follicle undergoes
following developmental changes:
• Granulosa cells, which are flat (spindle-shaped) in
primordial follicle become columnar and undergo
mitotic division to form a multilayered stratum
granulosum.
• Oocyte enlarges and becomes about 20 μm in size.
• Zona pellucida, a homogeneous membrane appears
consisting of glycoprotein between the granulosa
(follicular) cells and the oocyte. With the appearance
of zona pellucida, the follicle is now referred to as a
multilaminar primary follicle.
 3. Secondary follicle
• is formed from the primary follicle when:
• Granulosa cells undergo further proliferation.
• Oocyte further increases in size up to 100 μm. Its
nucleus becomes larger and vesicular forming
germinal spots.
• Theca folliculi or follicular sheath is formed outside
the basal lamina from the spindle-shaped cells from
the stroma of cortex in ovary. The theca folliculi
consist of an inner rim of secretory cells called theca
interna and an outer rim of thickly packed fibres
and spindle-shaped cells called theca externa (that
merges with the surrounding stroma).
 4. Tertiary follicle
• After proliferation, the granulosa cells start
secreting follicular fluid; this causes cavity to be
formed in the stratum granulosum (cavitation),
which is called antrum or follicular cavity.
• The fluid filled in the antrum is called liquor folliculi
which also contains oestrogen.
• The granulosa cells continue to proliferate and the
size of follicle is increased
 5. Graafian (antral) follicle
• After about 7th day of sexual cycle, one of the tertiary follicle
increases in size in response to FSH & LH and forms the mature
follicle called graafian or antral or vesicular follicle;
characterized by:
• Size of the follicle increases markedly to about 2–5 mm. The
growth of the graafian follicle is accomplished by granulosa and
theca proliferation.
• Antrum becomes larger.
• Theca interna becomes more prominent. The oestrogensecreting
cells of theca interna increase.
• Formation of secondary oocyte. Just prior to ovulation, the
primary oocyte of the fully matured graafian follicle completes
the first meiotic division (which began in fetal life at about 28th
week of gestation, i.e. before birth) and forms the secondary
oocyte with a haploid nucleus and the first polar body.
 MEIOSIS IN FEMALES

•(Recall that in males, each germinal cell produces

four haploid cells – each of which becomes a viable
sperm cell.)
•In females, only one of the resulting cells will be
viable and the other three recycled.
•After first meiotic division in females, each germinal
cell leads to two (diploid). (PRIMARY OOCYTE)
•After second meiotic division, the remaining largest
cell is the SECONDARY OOCYTE.
 OVARIAN HORMONES

• Ovary secretes the female sex hormones

estrogen and progesterone.
• Ovary also secretes few more hormones,
namely inhibin, relaxin and small quantities of
androgens.
 ESTROGEN

• Source of Secretion: In a normal non-pregnant woman, estrogen is

secreted in large quantity by theca interna cells of ovarian follicles
and in small quantity by corpus luteum of the ovaries.
• Estrogen secretion is predominant at the later stage of follicular
phase before ovulation.
• Estrogen is derived from androgens, particularly androstenedione,
which is secreted in theca interna cells.
• Androstenedione migrates from theca cells to granulosa cells,
where it is converted into estrogen by the activity of the enzyme
aromatase.
• A small quantity of estrogen is also secreted by adrenal cortex. In
pregnant woman, a large amount of estrogen is secreted by the
placenta.
Chemistry: Estrogen is a C18 steroid.
 Different Forms

• Oestrogens are (C-18) steroids. The naturally

occurring oestrogens include:
• Oestradiol. It is the principal and physiologically
most potent oestrogen. Ovarian oestradiol
accounts for more than 90% of the circulating
oestrogens.
• Oestrone. It is a weak ovarian oestrogen.
• Oestriol. It is the degradation product of
oestradiol and oestrone. It is the weakest of all
naturally occurring oestrogens.
 Synthesis, plasma levels and transport of oestrogens

• Sites. In the normal non-pregnant female, oestrogens are mainly

secreted by theca interna and granulosa cells of the ovarian follicles. A
small quantity is also produced by adrenal cortex, breast, some areas
of brain, placenta (during pregnancy), and by Sertoli cells (in males).
Biosynthesis. The salient points of oestrogen synthesis are:
• Oestrogens are mainly synthesized from cholesterol derived from
blood and to a slight extent from acetyl co-enzyme A.
• During synthesis progesterone and testosterone are synthesized first
and then these are converted into oestrogens.
• During synthesis progesterone and testosterone are synthesized first
and then these are converted into oestrogens.
• There are two pathways (Δ5 pathway and Δ4 pathway) for oestrogen
synthesis. The first step, i.e. (the conversion of cholesterol into
pregnenolone is common in both the pathways. This reaction is
stimulated by gonadotropins (FSH and LH).
FIGURE: Biosynthesis and metabolism of oestrogen
 △5 pathway
This pathway involves:
• Synthesis of 17 α hydroxypregnenolone and
dihydroxyepiandrosterone (DHEA). The reactions are catalyzed by
enzymes 17α-hydroxylase and 17, 20-hydroxylase respectively (CYP-
17).
• Note. CYP-17 is an enzyme which catalyses hydroxylation of C-17 and
cleavage of 2 carbon side chain at C-17 of pregnenolone and
progesterone.
• Then DHEA (17 ketosteroid) is converted to androstenedione
(another androgenic 17 ketosteroid) by an enzyme 3B hydroxysteroid
dehydrogenase (3BHSD) and Δ5 reductase.
• Androstenedione is then converted into testosterone by17-
hydroxysteroid dehydrogenase. This reaction is reversible.
• Testosterone is a precursor for oestradiol formation by aromatase
(CYP-19) enzyme.
 △4 pathway.
• In this pathway, progesterone is the initial
compound which is formed from pregnenolone by 3
B hydroxysteroid dehydrogenase and Δ5 isomerase.
• • Then progesterone is converted to 17α hydro-
xyprogesterone by 17 α-hydroxylase (CYP-17). 17α-
hydroxyprogesterone is another precursor for
androstenedione via 17–20 hydroxylase.
• • Then both androstenedione and testosterone are
converted to oestradiol and oestrone by aromatases
(CYP-19).
 Mechanism of biosynthesis of oestrogen 
• Gonadotropins (FSH and LH) from anterior pituitary stimulate the
synthesis of female sex hormones by acting on the receptors.
• Theca interna cells have many Luteinizing hormone (LH) receptors. The LH
therefore increases the conversion of cholesterol to androstenedione via
cyclic AMP.
• The granulosa cells also possess many FSH receptors. FSH, therefore,
facilitates the secretion of oestradiol by acting on these receptors through
activation of cyclic AMP, which increases the activity of aromatase
enzyme. The mature granulosa cells also acquire LH receptors; therefore,
LH stimulates the oestradiol production from granulosa cells also.
• There exists an interaction between theca interna and granulosa cells for
oestrogen synthesis. The granulosa cells can synthesize oestradiol only
when androstenedione is provided to them. The theca interna cells
provide supply of androstenedione to granulosa cells.
• In primates, it seems that the oestradiol present in the follicular fluid
comes from the granulosa cells. The stromal tissue of the ovaries can also
synthesize androgens and oestrogens in insignificant amounts.
FIGURE:
Interaction
between
theca interna
and
granulosa
cells for
synthesis of
oestradiol.
 Plasma levels 
• In a normal adult woman, the plasma levels of oestrogen
varies in different phases of the ovarian cycle (Fig. 9.3-
8, Table 9.3-1). As shown in Figure 9.3-8D, there are two
peaks of oestrogen secretion. The first occurs just before the
ovulation (12–13th day of a sexual cycle) and is
called oestrogen surge, and the second peak occurs in the
mid luteal phase. The secretion rate of oestrogen in
different phases is:
• In early follicular phase : 36 µg/day,
• Just before ovulation : 380 µg/day and
• During mid luteal phase : 250 µg/day.
• After menopause the oestrogen level falls to minimum of 50
µg/day.
FIGURE: (A) Correlation
of plasma concentration
of gonadotropins (FSH
and LH) ;(B) ovarian
cycle
changes; ; (C) basal
body
temperature; (D) ovaria
n hormones; (E) and
endometrial changes
during female sexual
cycle.
TABLE: Plasma Levels and Production Rate of Ovarian Hormones
Hormone Early follicular phase Preovulatory phase Mid luteal phase
Plasma Production Plasma Production Plasma Production
concentratio rate µg/day concentratio rate µg/day concentratio rate µg/day
n ng/dL n ng/dL n ng/dL
Oestrogens (C-18)
• Oestradiol 6 36 50 380 20 250
• Oestrone 5 50 20 350 10 250
Progesterone
(C-21) 9 1000 100 2000 1000 25,000
• 17α 30 600 200 4000 200 4000
Hydroxyprog
esterone
Androgens (C-19)
• Testostero 40 144 40 171 40 126
ne
• Androsten 150 2600 150 4700 150 3400
edione
• Dehydroep 500 7000 500 7000 500 7000
iandrosteron
e
 Transport 

• In the circulation oestrogens is present in two forms, bound

(98%),and free (2%). The oestradiol is mainly bound to plasma
proteins: 60% to albumin and 38% to β globulin. The β-globulin is
also known as gonadal steroid binding globulin (GBG) protein. It is
the same protein to which testosterone binds.
Metabolism and excretion of oestrogens. The liver is the main site for
metabolism of ovarian hormones. It involves following steps:
• Catabolism. Large quantities of oestrogens (oestradiol and oestrone)
are hydroxylated at C-16 position to form oestriol (an unpotent
degradation product). A small quantity of oestrogens is catabolized
by hydroxylation at C-2 and C-4 positions to form catechol
oestrogens.
• Conjugation. In the liver, the degradation metabolites are conjugated
with glucuronic acid and sulphuric acid to form water soluble
compounds (glucuronides and sulphates of oestriol and
catecholestriole).
• Excretion. Most (4/5th) of the water soluble compounds of
oestrogens are excreted by kidney into the urine and small amount
(1/5th part) of them is secreted into the bile and gets reabsorbed
 Functions of oestrogens 
• T​ he functions of oestrogen for descriptive purposes can be
grouped as: reproductive actions and other actions.
I. Reproductive actions 
A. During embryonic life: like testosterone (in males) oestrogen
has no effect on sex differentiation (gonadal and genital sex).
B. During pre-pubertal stage: During girlhood period, the
oestrogens are secreted in very small amount which have little
physiological actions.
C. At puberty: oestradiol is secreted in larger amounts which cause
following changes:
1. Growth and development of genital organs
i. Ovaries increase in size and complete ovarian cycles start which
are characterized by folliculosis, ovulation and corpus luteum
formation.
ii. Fallopian tubes become functional and show certain changes
such as epithelium becomes more cilliated, motility of fallopian
tubes also increases at ovulation to transport shedded gametes.
 iii. Uterus. The following changes occur in the uterus:
- Size. It enlarges in size, the smooth muscle fibres in myometrial
coat increase in number and in size, the contractile protein
contents also increase and the muscle fibres become active
and excitable.
- Endometrium gets thickened due to increase in stroma and
blood flow. The rhythmic cyclic changes (proliferative and
secretory) occur with the onset of menstrual cycle.
iv. Cervix also enlarges and with the onset of menstrual cycle,
endocervix undergoes cyclic changes (see page 852).
v. Vagina increases in size. Its epithelial lining increases in height
(from 2–3 layer cuboidal epithelium to 10–12 layers cornified
squamous epithelium). Vaginal epithelium is quite sensitive to
oestrogen and thus show cyclic changes during sexual cycle.
vi. External genitalia. The following changes occur in external
genitalia:
- Increase in size of clitoris,
- Labia majora and labia minora increase in size and get widened.
 C. At puberty cont’

2. Appearance of secondary sex characters.

Oestrogen is responsible for appearance
of secondary sex characters:
• In an adult woman, oestrogens along with
progesterone regulate the ovarian cycle, menstrual
cycle and cyclic changes in cervix, vagina and
fallopian tubes in a non-pregnant state.
• It plays an important role in maintenance of
pregnancy and then during parturition.
• It is important for breast development
 II. Other actions 

• The other functions of oestrogens include the effects on following:

1. Effects on bones
i. Oestradiol accelerates the linear growth of bones at puberty by its
osteoblastic activity. The epiphyseal centres are more sensitive to
oestrogen than testosterone; for this reason, average height of females is
little less than the males.
ii. Oestradiol enlarges the hip and widens the inlet of the pelvic bone to
facilitate child birth.
iii. Oestrogens maintain balance between bone formation and bone
resorption by following ways:
- It promotes bone formation by deposition of bone matrix by causing
Ca2+ and HPO42– retention and
- Inhibits bone resorption by inhibiting the production of osteoclasts and
their activity. These effects are achieved by inhibiting the production of
lymphokines such as interleukin-I (IL-1), TNF α, and granulocyte-
macrophage colony stimulating factor which promote proliferation of
osteoclasts.
• Note. Loss of oestrogen actions after menopause shifts the bone balance
towards bone resorption, thus causing osteoporosis 
 II. Other actions cont’

2. Effects on metabolism
i. Protein metabolism
- Oestrogens cause positive nitrogen balance due to growth promoting
effect which causes slight increase in the total body proteins.
- Oestrogens also increase the he
- Oestrogens also increase the hepatic synthesis of certain circulating
proteins, such as: thyroxine binding globulin, cortisol binding
globulins, renin substrate, angiotensinogens, very low density
lipoproteins (VLDL),and high density lipoproteins.
ii. Fat metabolism
- Oestrogens cause fat deposition in subcutaneous tissues, in the
breasts and the thighs.
- Lower the plasma cholesterol level and low density lipids due to
increase in number of LDL receptors.
3. Water and electrolyte balance. Oestrogens like other steroids in
general, cause salt and water retention in the body and produce
premenstrual tension in some women.
 II. Other actions cont’
4. Effects on vasculature. In general oestrogens have vasodilator and anti-vasoconstrictor effects.
• The vasodilator effect is through local release of vasodilator substances like nitric oxide (NO),
prostaglandins E2 and prostacyclin, and
• The antivasoconstrictor effect is through inhibition of endothelin-1 release (a vasoconstrictor
agent).
• Note: At the end of luteal phase of menstrual cycle there is sudden fall in plasma concentration
of oestrogen which results in alterations in the balance of vasodilatation and anti
vasconstriction and thus initiates ischaemic necrosis during menstrual phase.
• Loss of vasodilator effect in postmenopausal women leads to increased risk of coronary heart
disease.
5. Effects on CNS: Oestrogens are responsible for oestrous behaviour in animals and also increase
the libido in human females
• Oestrogens also act on other areas of the brain and effect the neuronal discharge and thus
effect the brain functioning. It has been observed that in mice oestrogen improves the memory
and learning. Therefore, deficiency of oestrogen in postmenopausal women is associated with
defects in declarative memory and development of Alzheimer’s disease.
6. Effects on skin: Oestrogens make the skin soft and more vascular.
• It makes the sebaceous glands secretions thin and inhibits formation of black heads
(comedones) and acne. Therefore, synthetic oestrogens are used as a part of treatment in acne
• i. Hair distribution: Hair develops in the pubic region and axilla. In
7. E ffect onSec ondar ySexu alChara cters

females, pubic hair has the base of the triangle upwards. Body hair
growth is less. Scalp hair grows profusely
ii. Skin:Skin becomes soft and smooth. Vascularity of skin also
increases
iii. Body shape: Shoulders become narrow, hip broadens, thighs
converge and the arms diverge. Fat deposition increases in breasts
and buttocks
iv. Pelvis: a. Broadening of pelvis with increased transverse diameter; b.
Round or oval shape of pelvis
• c. Round or oval=shaped pelvic outlet. Thus, pelvis in females is
different from that of males, which is funnel shaped.
• iv. Voice: Larynx remains in prepubertal stage, which produces
high-pitch voice.
 Effect on Uterus

i. Enlargement of uterus to about double of its childhood size due to the proliferation of
endometrial cells
ii. Increase in the blood supply to endometrium
iii. Deposition of glycogen and fats in endometrium
iv. Proliferation and dilatation of blood vessels of endometrium
v. Proliferation and dilatation of the endometrial glands, which become more tortuous with
increased blood flow
vi. Increase in the spontaneous activity of the uterine muscles and their sensitivity to
oxytocin
vii. Increase in the contractility of the uterine muscles. All these changes prepare uterus for
pregnancy.
 Effect on Breast

i. Development of stromal tissues of breasts

ii. Growth of an extensive ductile system
iii. Deposition of fat in the ductile system.
All these effects prepare the breasts for lactation.
Estrogen causes development of lobules and
alveoli of the breasts, to some extent. However,
progesterone is necessary for the full growth of
breast and prolactin is necessary for its function.
 Effect on Vagina

i. Changes the vaginal epithelium from cuboidal into stratified

type; the stratified epithelium is more resistant to trauma
and infection
ii. Increases the layers of the vaginal epithelium by proliferation
iii. Reduces the pH of vagina, making it more acidic. All these
changes are necessary for the prevention of certain
common vaginal infections such as gonorrheal vaginitis.
Such infections can be cured by the administration of
estrogen.
 Effect on Fallopian Tubes

i. Acts on the mucosal lining of the fallopian tubes

and increases the number and size of the
epithelial cells, especially the ciliated epithelial
cells lining the fallopian tubes
ii. Increases the activity of the cilia, so that the
movement of ovum in the fallopian tube is
facilitated
iii. Enhances the proliferation of glandular tissues in
fallopian tubes. All these changes are necessary
for the fertilization of ovum.
 M e ch an is m o f acti o n o f o e s tro g e n s

• ​Oestrogens act by entering into the cell and then bind with cytoplasmic receptors.
Oestrogen receptors: Oestrogen receptors are of two types (ERα and ERβ) and are coded by two
different genes located on separate chromosomes.
• The oestrogen receptor α (ERα) are mainly present in the endometrium, breasts, pituitary gland
and adrenal glands, and in the testes and epididymis in males. Whereas oestrogen
receptors β (ER β) are located in the ovaries (granulosa cells), bones (osleoclasts), lungs, some
areas of brain and in prostate gland and urinary bladder in males.
• It has been suggested that the actions of oestrogen which are carried out by circulatory
oestrogens and through hypothalamo-pituitary-gonadal axis are mainly mediated through ERα
receptors and the actions of oestrogen present in the follicular antrum are mediated through
ERβ receptors.
• The receptors contain a heat shock protein (HSP). When oestrogen binds to the receptor the HSP
get displaced and oestrogen receptor complex so formed is transferred on to the nucleus of the
target cell.
• Then the oestrogen receptor get bound to oestrogen response element present on the DNA
molecule
• Promotes the synthesis of new mRNA and that in turn directs the synthesis of new proteins
which modify the target cell activity.
• Note. Most of the actions of oestrogens are mediated via genomic receptors (ERα and ERβ).
However, some of its effects are so rapid (e.g. effect on brain neuronal discharge and feedback
effect on gonadotropins release that they might be mediated through non-genomic receptors
present on the plasma membrane.
 Synthetic oestrogens

Types. Various types of synthetic preparations of oestrogen available are:

1. Ethinyl derivatives of oestradiol such as diethylstilbestrol and ethinyloestradiol are
the potent oestrogens when given orally (because these are not metabolized in the
liver like natural oestrogens).
2. Plant oestrogens. Oestrogenic substances also present in plants, these rarely cause
adverse effects in human beings but when administered in animal they cause adverse
effects.
3. Nonsteroidal preparations also have oestrogenic activity.
Therapeutic uses.  The oestrogenic preparations are used under following conditions:
• To reduce menopausal symptoms like hot flushes.
• To prevent postmenopausal osteoporosis.
• To prevent progression to atherosclerosis and incidence of heart attacks and strokes.
• As contraceptive when used along with progesterone.
• Side effects (adverse effects). They stimulate growth of endometrium and breast and
thus increase the incidence of carcinoma of breast and of uterus. The compounds
like tamoxifen and raloxifene are under trial. It has been suggested that these
compounds are effective to check osteoporosis and have cardiovascular effects as that
of oestradiol but do not have growth promoting effect on uterus and cervix.
 Re gulation of Estr oge n Se creti on

• secretion is regulated by FSH released from anterior

pituitary.
• Release of FSH is stimulated by GnRH secreted from
hypothalamus.
• Theca cells and granulosa cells have many FSH receptors.
• After binding with the receptors, FSH acts via cAMP and
stimulates the secretory activities of theca and granulosa
cells.
• Estrogen inhibits secretion of FSH and GnRH by negative
feedback.
• Inhibin secreted by granulosa cells also decreases estrogen
secretion, by inhibiting the secretion of FSH and GnRH
 PROGESTERONE

• Progesterone is C-21 steroid meant for maintenance of

pregnancy and biologically called prostagen or gestagen.
• Synthesis, plasma levels and transport of progesterone
• Sites. In a normal adult nonpregnent woman
progesterone is mainly secreted by corpus luteum and
during pregnancy by the placenta. A small amount is also
secreted by adrenal cortex and by testes in case of males.
• Biosynthesis. Progesterone is synthesized from
cholesterol. Progesterone itself is an important
intermediary compound formed during biosynthesis of
steroids (oestrogens and androgens).
 Plasma levels. 

• In a normal adult woman, the plasma levels of progesterone varies

with different phases of sexual cycle.
• In early follicular phase, plasma concentration of progesterone is
very low (about 0.9 ng/ml or 9 ng/dL). About 80–90% of the
progesterone is derived from the conversion of adrenal DHEA and
androstenedione. But a large amount is also present in the
follicular antrum.
• In mid-cycle (late follicular phase), its level starts rising due to
secretion from the granulosa cells and it is mainly 17α-
hydroxyprogesterone and
• In luteal phase it reaches to its peak value, i.e. 18 ng/ml and
• At the end of cycle its levels fall to its minimum value.
• During pregnancy, the levels of progesterone further rise.
• After menopause. Progesterone levels fall to its minimum (0.2
ng/ml) or even not detectable.
 Transport 
• In the plasma progesterone is present in two forms:
• • Bound form. About 98% of progesterone in the
blood is present in bound form with plasma proteins.
With albumin (80%) and with corticoid binding
protein (CBP) also known as transcortin (18%). Hence,
progesterone is mostly present in loosely bound form
with albumin.
• • Unbound form or free form. Only 2% of circulating
progesterone is present in this form.
 Metabolism and excretion of progesterone

Metabolism. In the liver, progesterone is metabolized

to form pregnanediol and 17α-hydroxyprogesterone
to pregnanetriol.
• The metabolites then conjugated with glucuronic
acid and sulphuric acid to form water soluble
substances.
Excretion. The water soluble substance (glucuronides
and sulphates) of pregnanediol and pregnanetriol
are excreted by the kidney into the urine and small
amount is also secreted into the bile.
 Functions of progesterone

• The physiological actions of progesterone can be grouped as reproductive actions and

other actions.
I. Reproductive actions. 
• Reproductive actions are mainly on the reproductive organs primed by oestrogens
and these include:
1. Action on uterus. Under the influence of progesterone uterus shows following
changes:
Endometrium: Progesterone slows the proliferation of endometrial cells by decreasing
mitotic activity of the cells.
• The thickness of endometrium also increases.
• The endometrial glands become tortuous and contain 
• The endometrial glands become tortuous and contain fluid containing glycogen,
glycoproteins and glycolipids which provide nutrition to blastula if fertilization occurs.
• The glandular cells show vacuolation near their bases and the vacuolations move
from peripheral part towards the lumen of the gland.
• The spiral arteries become more coiled.
• The stroma of endometrium becomes oedematous.
 I. Reproductive actions cont’
• Thus, progesterone is responsible for secretory phase of the endometrial cycle and
prepares the endometrium to receive the zygote.
• Uterine motility. Progesterone decreases the uterine motility by following ways:
• It has antiestrogenic effect on the myometrial cells, decreasing the excitability
sensitivity to oxytocin and spontaneous electrical activity and increasing membrane
potential.
- It decreases the synthesis of voltage dependent Ca2+ channel proteins, therefore
Ca2+ uptake decreases.
- It decreases the number of oestrogen receptors on the myometrium.
2. Endocervix. The cervical secretions become thick and viscid, and ferning pattern
disappears.
3. Vagina. Vaginal epithelium becomes thickened, cornified and infiltrated with
leucocytes.
4. Fallopian tubes. Progesterone increases the beating rate of cilia of fallopian tubes
towards the uterus. The epithelial cell secretions also increase in amount and are
rich in nutritive materials to provide nutrition to a shedded ovum, incoming sperm
or to zygote if fertilization occurs.
5. Breast. Progesterone causes lobular and alveolar growth (see page 881) of breast.
6. During pregnancy. the main function of progesterone is to maintain the pregnancy 
 II. Other actions. 

• The other systemic effects of progesterone are:

1. Thermogenic effect. Progesterone is known as a thermogenic steroid
which increases the basal body temperature by 0.5°C in the
postovulatory phase.
2. Effect on CNS. Progesterone alters the secretion and release of
various neurotransmitters in the hypothalamus and other areas of the
brain and thereby decreases the appetite and produces somnolence.
3. Effect on respiration. Progesterone increases the sensitivity of the
respiratory centre to carbon dioxide stimulation. Due to this fact the
pACO2 is slightly less in woman during luteal phase of sexual cycle.
Therefore progesterone is used in Pickwickian syndrome.
4. Effect on fat metabolism. Progesterone (particularly C-19
progesterone) decreases the serum HDL. Thus, it acts as a
proathrogenic agent.
5. Effect on kidney. Large dose of progesterone produces natriuresis, by
blocking action of aldosterone on kidney.
 Summary of functions of progesterone

1. Action on uterus:
i. is responsible for the secretory phase of the endometrial cycle and
prepares the endometrium to receive the zygote. It decreases the
uterine motility by:
a. It decreases the synthesis of voltage-dependent Ca2+ channel
proteins, therefore Ca2+ uptake decreases.
b. It decreases the number of oestrogen receptors on the myometrium.
ii. Increases the thickness of the endometrium by increasing the
number and size of the cells. Thickness of endometrium increases
from 1 mm thickness at the beginning of secretory phase to about 5
to 6 mm at the end of secretory phase.
iii. Increases the size of uterine glands and these glands become more
tortuous
iv. Increases the secretory activities of epithelial cells of uterine glands
 1. Action on uterus cont’
iv. Increases the deposition of lipid and glycogen in
the stromal cells of endometrium
v. Increases the blood supply to endometrium. It is
due to increase in size of the vessels and
vasodilatation
vi. Decreases the frequency of uterine contractions
during pregnancy. Because of this, the expulsion of
the implanted ovum is prevented.
 Me cha nis m of acti on

• The effects of the progesterone on its target cell is achieved by acting through its
receptors.
• The progesterone receptors are present in the cytoplasm of the target cells and
contain a protein called HSP.
• Being lipid progesterone easily enters through bilayer lipid membrane and
combines with its receptors.
• Then the HSP displaces and thus exposing the DNA binding site.
• Then the receptor progesterone complex get transferred on to the nucleus and
binds to a specific site on the DNA molecule, and
• Initiates encoding of gene expression to form new mRNA. The mRNA then directs
the apparatus to form new proteins (enzymes and structural proteins) which modify
the activities of the target cells.
Note. A synthetic steroid mifepristone (RU-486) binds to progesterone receptors and
blocks the DNA binding site. Therefore this drug acts as aantiprogesterone drug.
Synthetic preparations of progesterone. ​Various synthetic preparations are available
under the name prostagens and gestagens. Therapeutically these drugs are used in:
• Inevitable abortion
• As contraceptives when used along with oestrogens.
 O th er o va ria n h orm one s

• Besides female sex steroids (oestrogen and progesterone) ovaries also secrete
peptide hormones as:
1. Inhibin structurally it is polypeptide, it inhibits the FSH release.
2. Activin. Structurally, it is also a polypeptide; its action is to activate FSH
secretion from anterior pituitary.
3. Relaxin is a polypeptide hormone produced by corpus luteum and other sites
include: uterus, placenta and mammary glands and in males from the prostate
gland. Its main role is during pregnancy as mentioned:
• It relaxes pubic symphysis and pelvic joints, softens and dilates the uterine
cervix and facilitates delivery.
• In non-pregnant state it releases from the corpus luteum and endometrium
during secretory phase its function is not known.
• In males relaxin is present in the semen and helps in sperm motility and
penetration of ovum by the sperm.
4. Ovarian androgens. A small amount of testosterone is also secreted by the
ovaries during biosynthesis of oestrogen and progesterone, but the main source
of androgens in female is adrenal cortex. These androgens are responsible for
acne vulgaris, libido, and pubic hair.
• Is cyclic events that take place in a rhythmic fashion during the
M ENS TR U AL C YC LE

reproductive period of a woman’s life. Starts at the age of 12 to 15

years, which marks the onset of puberty.
• ceases at the age of 45 to 50 years. Permanent cessation in old age is
called menopause.
• During each cycle, series of changes occur in ovary and accessory sex
organs; divided into 4 groups:
1. Ovarian changes
2. Uterine changes
3. Vaginal change
4. Changes in cervix.
5. Other changes during sexual cycle
All these changes take place simultaneously. Traditionally, first day of
the menstrual bleeding is taken as the 1st day of female sexual cycle.
 OVARIAN CHANGES DURING MENSTRUAL CYCLE

• Changes in the ovary during each cycle occur in two phases:

A. Follicular phase and B. Luteal phase.
Ovulation occurs in between these two phases.
FOLLICULAR PHASE: extends from the 5th day of the cycle
until the time of ovulation, which takes place on 14th day.
Maturation of ovum with development of ovarian follicles
takes place during this phase, generally lasts for 8–9 days (but
may vary from 10 to 25 days).
Ovarian Follicles: are glandular structures present in the
cortex of ovary. Each follicle consists of the ovum surrounded
by granulosa cells. The follicles gradually grow into a matured
follicle through various stages.
 Different follicles

• 1. Primordial follicle
2. Primary follicle
3. Vesicular follicle
4. Matured follicle or graafin follicle.
 1. Primordial Follicle

• At the time of puberty, both the ovaries contain about

400,000 primordial follicles. Diameter of the primordial
follicle is about 15 to 20 µ and that of ovum is about 10µ.
Each primordial follicle has an ovum, which is incompletely
surrounded by the granulosa cells. These cells provide
nutrition to the ovum during childhood. The primordial
follicles lack a direct blood supply.
• Granulosa cells also secrete the oocyte maturation inhibiting
factor, which keeps ovum in the immature stage. All the ova
present in the ovaries are formed before birth. No new ovum
is developed after birth. At the onset of puberty, under the
influence of FSH and LH the primordial follicles start growing
through various stages.
 2 . P rima ry Fo l licle

• Primordial follicle becomes the primary follicle, when ovum

is completely surrounded by the granulosa cells. During this
stage, the follicle and the ovum increase in size. Diameter
of the follicle increases to 30 to 40 µ and that of ovum
increases to about 20 µ. The follicle is not covered by a
definite connective tissue capsule.
Changes taking place during development of primary follicle
i. Proliferation of granulosa cells and increase in size of the
follicle
ii. Increase in size of the ovum
iii. Onset of formation of connective tissue capsule around the
follicle, develop into vesicular follicles.
 3. Secondary follicle

• is formed from the primary follicle when following changes

occur:
i. Granulosa cells undergo further proliferation.
ii. Oocyte further increases in size upto 100 µ. Its nucleus
becomes larger and vesicular, forming germinal spots.
iii. Theca folliculi  is formed outside the basal lamina from the
spindle-shaped cells from the stroma of cortex in ovary. The
theca folliculi consist of an inner rim of secretory cells
called theca interna and an outer rim of thickly packed fibres
and spindle-shaped cells called theca externa .
iv. independent blood supply consisting of arterioles that do not
penetrate the basal lamina is acquired by the secondary
follicles.
 4. Tertiary follicle

• is characterized by following features:

• Formation of antrum. After proliferation, the
granulosa cells start secreting follicular fluid, this
causes cavity to be formed in the stratum
granulosum (cavitation), which is called antrum or
follicular cavity. The fluid filled in the antrum is
called liquor folliculi which also contains oestrogen.
The granulosa cells continue to proliferate and the
size of follicle is increased
 i. Ch anges ingra nulosa cells

i. First, the proliferation of granulosa cells occurs

ii. A cavity called follicular cavity or antrum is formed in between
the granulosa cells
iii. Antrum is filed with a serous fluid called the liquor folliculi
iv. With continuous proliferation of granulosa cells, the follicle
increases in size
v. Antrum with its fluid also increases in size
vi. Ovum is pushed to one side and it is surrounded by granulosa
cells, which forms the germ hill or cumulus oophorus
vii. Granulosa cells, which line the antrum form membrana
granulosa
viii.Cells of germ hill become columnar and form corona radiata.
 ii. Chan ges in ovu m

i. First, the ovum increases in size and its diameter

increases to 100 to 150 µ
ii. Nucleus becomes larger and vesicular
iii. Cytoplasm becomes granular
iv. Thick membrane is formed around the ovum,
which is called zona pellucida
v. A narrow cleft appears between ovum and zona
pellucida. This cleft is called perivitelline space.
 Formation of capsule
• Spindle cells from the stroma of ovarian cortex are
modified and form a covering sheath around the
follicle. The covering sheath is known as follicular
sheath or theca folliculi. Theca folliculi divides into
two layers:
a. Theca interna
b. Theca externa.
 a. Theca interna
• is the inner vascular layer with loose connective
tissue.
• This layer also contains special type of epithelial
cells with lipid granules and some delicate collagen
fibers.
• Epithelial cells become secretory in nature and start
secreting the female sex hormones, especially
estrogen.
• Hormones are released into the fluid of antrum.
 b. Theca externa
• is the outer layer of follicular capsule and consists of
thickly packed fibers and spindle-shaped cells.
• After about 7th day of the cycle, one of the
vesicular follicles outgrows others and becomes the
dominant follicle.
• It develops further to form graafian follicle.
• Other vesicular follicles degenerate and become
atretic by means of apoptosis.
 5. Graafian (antral) follicle
• After about seventh day of sexual cycle, one of the tertiary
follicle increases in size in response to gonadotropins (both
FSH and LH) and forms the mature follicle called graafian or
antral or vesicular follicle.
• It is uncertain how one follicle is selected to become the
mature graafian follicle in this follicular phase of the cycle,
but it seems to be related to the ability of the follicle to
secrete the oestrogen inside it that is needed for final
maturation.
• Rest of the follicles degenerate and become atrophied by
apoptosis.
 5. Graafian Follicle (the matured ovarian follicle )
• Changes taking place:
i. Size of the follicle increases to about 10 to 12 mm. It
extends through the whole thickness of ovarian
cortex
ii. the follicle encroaches upon tunica albuginea and
protrudes upon surface of the ovary. This protrusion
is called stigma. At the stigma, the tunica albuginea
becomes thin
iii. Follicular cavity becomes larger and distended with
fluid
iv. Ovum attains maximum size
 Ch ang es tak ing p lace co nt’ :

v. Zona pellucida becomes thick

vi. Corona radiata becomes prominent
vii. Small spaces filed with fluid appear between the
cells of germ hill, outside the corona radiata. These
spaces weaken the attachment of the ovum to the
follicular wall
viii. Theca interna becomes prominent. Its thickness
becomes double with the formation of rich capillary
network
ix. On the 14th day of menstrual cycle, graafian follicle
is ready for the process of ovulation.
 OVULATION

• is the process by which the graafian follicle ruptures with

consequent discharge of ovum into the abdominal cavity. It
is influenced by LH.
• Ovulation occurs on 14th day of menstrual cycle in a normal
cycle of 28 days. The ovum, which is released into the
abdominal cavity, enters the fallopian tube through the
fimbriated end of the tube. Usually, only one ovum is
released from
any one of the ovaries.
• Prior to ovulation, large amount of LH is secreted (luteal
surge).
• This causes changes in the graafian follicle leading to
ovulation.
 Stages of Ovulation
1. Graafian follicle moves towards the periphery of ovary
2. New blood vessels are formed in the ovary by actions
of LH and progesterone
3. These blood vessels protrude into the wall of the
follicle
4. This increases the blood flow to the follicle
5. Now, prostaglandin is released from granulosa cells of
the follicle
6. It causes leakage of plasma into the follicle
7. Just before ovulation the follicle swells and protrudes
against the capsule of the ovary. This protrusion is
called stigma
 Stages of Ovulation cont’

8. Then, progesterone activates the proteolytic

enzymes present in the cells of theca interna
9. These enzymes weaken the follicular capsule and
cause degeneration of the stigma
10. After about 30 minutes, fluid begins to ooze from
the follicle through the stigma
11. It decreases the size of the follicle causing rupture
of stigma;
12. Now, ovum is released from the follicle along with
fluid and plenty of small granulosa cells into the
abdominal cavity.
 DETERMINATION OF OVULATION TIME
• Various methods are available to determine the
ovulation time. In human beings, usually indirect
methods are adopted such as:
1. Determination of basal body temperature
2. Determination of hormonal excretion in urine
3. Determination of hormonal level in plasma
4. Ultrasound scanning
5. Cervical mucus pattern.
 DETERMINATION OF BASAL BODY TEMPERATURE
• Body temperature is measured for few days during
the mid period of menstrual cycle.
• Temperature is measured in the morning by placing
the thermometer in rectum or vagina.
• There is a slight fall in the basal temperature just
prior to ovulation. And the temperature increases
after ovulation.
• The alteration in the temperature is very mild and it
is about ± 0.3°C to 0.5°C.
• The increase in temperature is due to the
thermogenic effect of progesterone.
 DETERMINATION OF HORMONAL EXCRETION IN URINE

• At the time of ovulation, there is an increase in the

urinary excretion of metabolic end products of
estrogen and progesterone.
• The end products of estrogen metabolism are
estrone, estriol and 17-β-estradiol.
• The end product of progesterone metabolism is
pregnanediol.
DETERMINATION OF HORMONAL LEVEL IN PLASMA
• Plasma level of FSH, LH, estrogen and
progesterone is measured. Hormone level is
altered at the time of ovulation and after
ovulation.
At the time of ovulation:
i. FSH level decreases
ii. LH level increases
iii. Estrogen level increases.
After ovulation: Progesterone level increases.
 DETERMINATION OF OVULATION TIME CONT’

• ULTRASOUND SCANNING: Process of ovulation can

be observed in ultrasound scanning.
• CERVICAL MUCUS PATTERN: When the cervical
mucus spread on a slide is examined under
microscope, it shows a fern pattern. This pattern
disappears after ovulation.
• SIGNIFICANCE OF DETERMINING OVULATION
TIME: Determination of ovulation time is helpful for
family planning by rhythm method
 LUTEAL PHASE (POST-OVULATORY PHASE)

• extends between 15th and 28th day of menstrual

cycle (is of remarkably constant period of about 14
days).
• During this phase, corpus luteum is developed
• Corpus luteum is a glandular yellow body,
developed from the ruptured graafian follicle after
the release of ovum. It is also called yellow body.
 Development of Corpus Luteum
• Soon after the rupture of graafian follicle and release of
ovum, the follicle is filled with blood. Now the follicle is
called corpus hemorrhagicum. The blood clots slowly.
• Corpus hemorrhagicum does not degenerate
immediately. It is transformed into corpus luteum.
• Follicular cavity closes gradually by the healing of the
wound.
• Blood clot is gradually replaced by a serous fluid
containing fibrin. Corpus luteum obtains a diameter of
15 mm and remains in the ovary till the end of the
cycle.
 Structure of Corpus Luteum
• In the corpus luteum, granulosa cells and theca interna cells
are transformed into lutein cells called granulosa lutein cells
and theca lutein cells.
• The process which transforms the granulosa and theca cells
into lutein cells is called luteinization.
• Granulosa lutein cells contain fine lipid granules and the
yellowish pigment granules.
• The yellowish pigment granules give the characteristic yellow
color to corpus luteum.
• Theca lutein cells contain only lipid granules and
not the yellow pigment. Follicular cavity is greatly reduced
with irregular outline. It is filed with the serous fluid and
remnants of blood clots.
 Functions of Corpus Luteum
1. Secretion of hormones: Corpus luteum acts as a
temporary endocrine gland. It secretes large quantity of
progesterone and small amount of estrogen. Granulosa
lutein cells secrete progesterone and theca lutein cells
secrete estrogen. LH influences the secretion of these
two hormones.
2. Maintenance of pregnancy: If pregnancy occurs, corpus
luteum remains active for about 3 months, i.e. until
placenta develops. Hormones secreted by corpus
luteum during this period maintain the pregnancy.
Abortion occurs if corpus luteum becomes inactive or
removed before third month of pregnancy, i.e. before
placenta starts secreting the hormones.
 Fate of Corpus Luteum
• If there is no fertilization and pregnancy does not
occur, the corpus luteum reaches the maximum size
about one week after ovulation. During this period,
it secretes large quantity of progesterone with small
quantity of estrogen.
• Then, it degenerates into the corpus luteum
menstrualis or spurium. The cells decrease in size
and the corpus luteum becomes smaller and
involuted.
• The process by which corpus luteum undergoes
regression is called luteolysis.
 Fate of Corpus Luteum cont’
• Then, the corpus luteum begins to involute (regress) after
24th day of the sexual cycle and is eventually replaced by a
whitish scar tissue called the corpus albicans.
• This involution occurs due to falling levels of FSH and LH
and also the hormone inhibin secreted by the lutein cells.
• With the involution of corpus luteum, on 26th day of the
normal female sexual cycle, levels of oestrogen,
progesterone and inhibin fall.
• This removes feedback inhibition of the anterior pituitary;
consequently, the FSH and within a few days LH secretion
begins and the next ovarian cycle is initiated.
 Fate of Corpus Luteum cont’
• If ovum is fertilized and pregnancy occurs, the corpus
luteum persists and increases in size.
• It attains a diameter of 20 to 30 mm and it is transformed
into corpus luteum graviditatis (verum) or corpus luteum
of pregnancy.
• It remains in the ovary for 3 to 4 months. During this
period, it secretes large amount of progesterone with small
quantity of estrogen, which are essential for the
maintenance of pregnancy.
• After 3 to 4 months, placenta starts secreting these
hormones and corpus luteum degenerates.
 ENDOMETRIAL CYCLE (UTERINE CYCLE)

• refers to the cyclic changes occurring in the endometrium

during active reproductive period (menarche to menopause)
in females leading to recurrent monthly bleeding per vaginum
(menstruation).
• These cyclic changes in the endometrium are brought about
by the cyclic production of oestrogens and progesterone by
the ovaries. Menstrual is a Latin word meaning mensis, i.e.
lunar month of 28 days.
• Though the menstrual cycle for description purposes is
considered to be of 28 days, but the cycle is by no means as
regular as the name suggests. The menstrual cycles of 25 to
35 days are also regarded as normal cycles.
ENDOMETRIAL CYCLE (UTERINE CYCLE) CONT’
• During each menstrual cycle, along with
ovarian changes, uterine changes also occur
simultaneously. Uterine changes occur in
three phases:
1. Menstrual phase (1st to 5th day
2. Proliferative phase (6th to 14th day)
3. Secretory phase.(15th to 28th day)
 MENSTRUAL PHASE
• After ovulation, if pregnancy does not occur, the thickened
endometrium is shed or desquamated.
• This desquamated endometrium is expelled out through vagina along
with blood and tissue fluid.
• The process of shedding and exit of uterine lining along with blood
and fluid is called menstruation or menstrual bleeding. It lasts for
about 3 to 5 days.
• This period is called menstrual phase or menstrual period. It is also
called menses, emmenia or catamenia.
• The day when bleeding starts is considered as the first day of the
menstrual cycle.
• Two days before the onset of bleeding, that is on 26th or 27th day of
the previous cycle, there is a sudden reduction in the release of
estrogen and progesterone from ovary. Decreased level of these two
hormones is responsible for menstruation.
 Changes in Endometrium during Menstrual Phase

i. Lack of estrogen and progesterone causes sudden involution of

endometrium; ii. It leads to reduction in the thickness of
endometrium, up to 65% of original thickness
iii. During the next 24 hours, the tortuous blood vessels in the
endometrium undergo severe constriction. Endometrial
vasoconstriction is because of three reasons:
a. Involution of endometrium; b. Actions of vasoconstrictor
substances like prostaglandin, released from tissues of involuted
endometrium; c. Sudden lack of estrogen and progesterone (which
are vasodilators)
iv. Vasoconstriction leads to hypoxia, which results in necrosis of the
endometrium
v. Necrosis causes rupture of blood vessels and oozing of blood. Blood
vessels get open up due to necrosis of their wall resulting in seepage
of blood into the surrounding endometrial necrotic tissue.
 Changes in Endometrium during Menstrual Phase
vi. Outer layer of the necrotic endometrium is separated and
passes out along with blood. The necrosis and sloughing
does not occur simultaneously in whole of the uterus
rather it occurs in patches and is completed in 3–5 days.
vii. Endometrial debris contains necrosed sloughed off tissue,
blood, serous fluid and a large amount of prostaglandins
and fibrolysins.
viii. Average amount of blood loss during each menstrual
cycle is 30 mL.
ix. Within 48 hours after the reduction in the secretion of
estrogen and progesterone, the superficial layers of
endometrium are completely desquamated
Changes in Endometrium during Menstrual Phase
x. Menstrual blood immediately gets clotted inside the
uterine cavity but soon gets liquefied by fibrolysins present
in the endometrial debris.
xi. Desquamated tissues and the blood in the endometrial
cavity initiate the contraction of uterus
xii. Uterine contractions expel the blood along with
desquamated uterine tissues to the exterior through
vagina.
xiii. During menstrual phase, about two-thirds of the
superficial endometrium is sloughed off and only a thin
basal layer (2 mm thick) is left behind.
 NOTE

• During normal menstruation, about 35 mL of blood along

with 35 mL of serous flid is expelled.The blood clots as soon
as it oozes into the uterine cavity.
• Fibrinolysin causes lysis of clot in uterine cavity itself, so
that the expelled menstrual fluid does not clot. However, in
the pathological conditions involving uterus, the lysis of
blood clot does not occur. So the menstrual fluid comes out
with blood clot.
• Menstruation stops between 3rd and 7th day of menstrual
cycle. At the end of menstrual phase, the thickness of
endometrium is only about 1 mm. This is followed by
proliferative phase.
 PROLIFERATIVE PHASE
• extends usually from 5th to 14th day of
menstruation, i.e. between the day when
menstruation stops and the day of ovulation.
• It corresponds to the follicular phase of ovarian
cycle.
• At the end of menstrual phase, only a thin layer (1
mm) of endometrium remains, as most of the
endometrial stroma is desquamated.
 C h a n g e s in En d o me triu m d u ri n gP ro l ifera tiv e P h a se

i. Endometrial cells proliferate rapidly

ii. Epithelium reappears on the surface of endometrium within
the fist 4 to 7 days
iii. Uterine glands start developing within the endometrial
stroma
iv. Blood vessels appear in the stroma
v. Proliferation of endometrial cells occurs continuously, so
that the endometrium reaches the thickness of 3 to 4 mm at
the end of proliferative phase. All these uterine changes
during proliferative phase occur because of the influence of
estrogen released from ovary. On 14th day, ovulation occurs
under the influence of LH. This is followed by secretory
phase.
 SECRETORY PHASE
• extends between 15th and 28th day of the cycle, i.e.
between the day of ovulation and the day when
menstruation of next cycle commences.
• After ovulation, corpus luteum develops & secretes a large
quantity of progesterone along with a small amount of
estrogen.
• Estrogen causes further proliferation of cells in uterus, so
that the endometrium becomes thicker.
• Progesterone causes further enlargement of endometrial
stroma and further growth of glands.
• Under the influence of progesterone, the endometrial
glands commence their secretory function. Many changes
occur in the endometrium before commencing the
secretory function.
 Changes in Endometrium during Secretory Phase
i. Endometrial glands become more tortuous. Because
of increase in size, the glands become tortuous to
get accommodated within the endometrium
ii. Cytoplasm of stromal cells increases because of the
deposition of glycogen and lipids
iii. Many new blood vessels appear within
endometrial stroma. Blood vessels also become
tortuous
iv. Blood supply to endometrium increases
v. Thickness of endometrium increases up to 6 mm.
 NOTE
• is the preparatory period, during which the uterus is
prepared for implantation of ovum.
• All these uterine changes occur due to the influence of
estrogen and progesterone.
• Estrogen is responsible for repair of damaged endometrium
and growth of the glands.
• Progesterone is responsible for further growth of these
structures and secretory activities in the endometrium.
• If a fertilized ovum is implanted during this phase and if the
implanted ovum starts developing into a fetus, then further
changes occur in the uterus for the survival of the
developing fetus.
 CHANGES IN CERVIX DURING MENSTRUAL CYCLE
• Proliferative Phase: the mucus membrane of cervix
becomes thinner and more alkaline due to the influence of
estrogen. It helps in the survival and motility of
spermatozoa. At the time of ovulation, the cervical mucus is
thinnest and its elasticity is maximum. It can be stretched
like a long, thin elastic thread up to 8–12 cm (spinnbarkeit
effect).
• Secretory Phase: the mucus membrane of cervix becomes
more thick and adhesive because of actions of
progesterone. These changes make a plug and prevent the
entry of sperm through cervical canal.
 Fern test

• The fern pattern of cervical mucus in the

proliferative phase and its disappearance in the
secretory phase is indicative of ovulatory cycle,
whereas persistence of fern pattern (Fig. 9.3-8D)
throughout the cycle indicates anovulatory cycle.
The mucus also produces a characteristic fern-like
pattern when a drop of mucus is spread on the glass
slide and allowed to dry (Fern test
 VAGINAL CHANGES DURING MENSTRUAL CYCLE

• Vaginal canal is lined by stratified squamous epithelium, which

is highly sensitive to oestrogens (oestradiol). Vaginal epithelium
undergoes following cyclic changes in the endometrial cycle:
• Proliferative Phase: Epithelial cells of vagina are cornified.
Estrogen is responsible for this. vaginal epithelium becomes
thickened (by adding up more and more layers of epithelium)
and cornified.
• Secretory Phase: Vaginal epithelium proliferates due to the
actions of progesterone. It is also infiltrated with leukocytes.
These two changes increase the resistance of vagina for
infection; under the influence of progesterone, vaginal
epithelium proliferates and gets infiltrated with leucocytes and
the vaginal secretions become thick and viscid.
 OTHER CHANGES DURING SEXUAL CYCLE
• Hormonal oscillations during sexual cycle though mainly effect
ovaries, uterus, cervix and vagina but some changes have also
been observed in the fallopian tubes, breast and in the body
weight.
1. Changes in fallopian tubes are as follows:
(i) During follicular phase, there occurs an increase in the number
of cilia of epithelial cells and their rate of beating. An increase in
the vascularization of fimbria.
(ii) At the time of ovulation, the motility of fallopian tubes
increases.
(iii) During luteal phase, under the influence of progesterone,
there occurs an increase in the secretion of epithelial cells. This
provides nutrition to the ovum, incoming sperm and the zygote
if fertilization occurs.
 OTHER CHANGES DURING SEXUAL CYCLE
2. Changes in breast. Some women complain of
feeling of fullness and tenderness in the breasts.
These symptoms have been related to the
proliferation of lobules and duct system under the
influence of oestrogen and progesterone. All these
symptoms regress during menstrual phase.
3. Pre-menstrual weight gain. Many women
experience feeling of heaviness (pre-menstrual
tension) near the end of cycle. This effect is due to
salt and water retention caused by the oestrogen.
The feeling of heaviness disappears during
menstruation phase.
 REGULATION OF MENSTRUAL CYCLE
• Regulation of menstrual cycle is a complex process
that is carried out by a well organized regulatory
system. The regulatory system is a highly integrated
system, which includes hypothalamus, anterior
pituitary and ovary with its growing follicle. In the
whole scenario, the growing follicle has a vital role
to play.
 HORMONES INVOLVED IN REGULATION
• The regulatory system functions through the
hormones of hypothalamo-pituitary-ovarian axis.
Hormones involved in the regulation of menstrual
cycle are:
1. Hypothalamic hormone: GnRH
2. Anterior pituitary hormones: FSH and LH
3. Ovarian hormones: Estrogen and progesterone.
 Hypothalamic Hormone – GnRH
• GnRH triggers the cyclic changes during menstrual
cycle by stimulating secretion of FSH and LH from
anterior pituitary. GnRH secretion depends upon
two factors:
i. External factors like psychosocial events, which act
on hypothalamus via cortex and many other brain
centers
ii. Feedback effects of ovarian changes via ovarian
hormones.
 Anterior Pituitary Hormones – FSH and LH
• FSH and LH modulate the ovarian and uterine
changes by acting directly and/or indirectly via
ovarian hormones. FSH stimulates the recruitment
and growth of immature ovarian follicles. LH
triggers ovulation and sustains corpus luteum.
Secretion of FSH and LH is under the influence of
GnRH.
• show many activities during menstrual cycle.
Ovarian Hormones – Estrogen and Progesterone

• Ovarian follicle secretes large quantity of estrogen and corpus

luteum secretes large quantity of progesterone.
• Estrogen secretion reaches the peak twice in each cycle; once
during follicular phase just before ovulation and another one
during luteal phase.
• On the other hand, progesterone is virtually absent during
follicular phase till prior to ovulation. But it plays a critical role
during luteal phase.
• Estrogen is responsible for the growth of follicles.
• Both the steroids act together to produce the changes in uterus,
cervix and vagina. Both the ovarian hormones are under the
influence of GnRH, which acts via FSH and LH. In addition, the
secretion of GnRH, FSH and LH is regulated by ovarian hormones.
 REGULATION OF OVARIAN CHANGES
• Follicular Phase
1. The biological clock responsible to trigger the cyclic events is the
pulsatile secretion of GnRH, at about every 2 hours (due to some
mechanism that is not understood clearly)
2. Pulsatile release of GnRH stimulates the secretion of FSH and LH
from anterior pituitary
3. LH induces the synthesis of androgens from theca cells of growing
follicle
4. FSH promotes aromatase activity in granulosa cells of the follicle,
resulting in the conversion of androgens into estrogen. It also
promotes follicular development
5. Estrogen is responsible for development and growth of graafian
follicle. It also stimulates the secretory activities of theca cells
 Follicular Phase cont’
6. Estrogen also exerts a double feedback control on GnRH
i. Initially, when estrogen secretion is moderate, it exerts a negative
feedback control on GnRH so that GnRH secretion is inhibited. This
leads to decrease in secretion of FSH and LH; ii. During later period of
follicular phase, when a large amount of estrogen is secreted by the
maturing follicle, it exerts a positive feedback effect on GnRH
secretion. Now, GnRH secretion is increased, resulting in secretion of
large quantity of FSH and LH. This in turn, facilitates the growth of
graafian follicle
7. In addition, estrogen shows the following actions:
i. Increases the number of FSH and LH receptors on the granulosa
cells of follicles and increases the sensitivity of these cells for FSH and
LH; ii. Facilitates the faster growth of graafian follicle
8. LH is necessary to provide the final touches for the growth of graafian
follicle. It stimulates the secretion of estrogen. At the same time, it
stimulates the theca cells to secrete progesterone.
 Regulation of ovulation

• LH is important for ovulation. Without LH,

ovulation does not occur even with a large
quantity of FSH. The need for excessive
secretion of LH for ovulation is known as
ovulatory surge for LH or luteal surge. Prior
to ovulation, a large quantity of LH is secreted
due to positive feedback effect of estrogen on
GnRH, as mentioned above.
 Regulation of Luteal Phase
• Role of LH: Ovarian changes during luteal phase depend
mainly on LH.
• LH: 1. Induces development of corpus luteum from the
follicle (devoid of ovum) by converting the granulosa cells
into lutein cells
2. Stimulates corpus luteum to secrete progesterone and
estrogen
3. Necessary for the maintenance of corpus luteum.
Role of FSH: also plays a role during luteal phase.
Follicle-stimulating hormone:
1. Maintains the secretory activity of corpus luteum
2. Stimulates lutein cells to secrete inhibin, which in turn
inhibits FSH secretion.
 If the ovum is not fertilized or if implantation of ovum does not take place

• Progesterone and estrogen secreted from corpus luteum, inhibit the

secretion of FSH and LH from anterior pituitary by negative feedback
• Granulosa lutein cells secrete another hormone called inhibin (which
is also secreted by Sertoli cells of testes in males: Inhibin also inhibits
the secretion of FSH and LH by negative feedback
• In the absence of FSH and LH, the corpus luteum becomes inactive
• Finally, the corpus luteum regresses by means of luteolysis; so
progesterone and estrogen are not available
• Absence of progesterone and estrogen induces the secretion of GnRH
from hypothalamus
• GnRH stimulates the secretion of FSH and LH from anterior pituitary.
FSH and LH stimulate the new immature follicles, resulting in the
commencement of next cycle.
 REGULATION OF UTERINE CHANGES
• Uterine changes during menstrual cycle are influenced by
estrogen and progesterone.
Proliferative Phase: the repair of the damaged
endometrium occurs mainly by estrogen. Estrogen
stimulates:
1. Proliferation of cells in endometrial stroma
2. Development of uterine glands and appearance of blood
vessels in the endometrial stroma.
Secretory Phase: coincides with luteal phase of ovarian
cycle. Under the influence of FSH and LH from anterior
pituitary, the corpus luteum secretes large amount of
progesterone and small amount of estrogen. Progesterone
is responsible for endometrial changes along with estrogen
during this phase.
 Progesterone stimulates

1. Growth of endometrial glands and makes them

more tortuous
2. Growth of blood vessels and makes them also
tortuous, leading to increase in blood flow to
endometrium
3. Secretory activities of endometrial glands.
Thus, during the secretory phase, the structure,
blood flow and secretory functions of uterus are
influenced by estrogen and progesterone secreted
by corpus luteum.
 Menstrual Phase -regulation
• If pregnancy does not occur, menstrual phase occurs:
1. During the last two days of secretory phase, i.e. two days prior
to onset of menstruation, the secretion of large quantity of
progesterone and estrogen from corpus luteum inhibits the
secretion of FSH and LH from anterior pituitary, by negative
feedback
2. In the absence of LH and FSH, the corpus luteum becomes
inactive and starts regressing
3. Sudden withdrawal of ovarian hormones progesterone and
estrogen occurs
4. It leads to menstrual bleeding. Lack of ovarian hormones
causes the release of gonadotropins once again from anterior
pituitary. It results in the onset of development of new follicles
in ovary and the cycle repeats.
 Re gul ation of gon ad otro pin s

• The secretion of both FSH and LH is regulated by:

• 1. Gonadal hormones: (oestrogen and progesterone) regulate
gonadotropin secretion by their feedback effect. Depending on
relative plasma level of these hormones, the effect may be positive or
negative.
• Oestrogen, in moderately high plasma concentration (just before
ovulation) inhibits the release of FSH and promotes LH secretion.
• High levels of oestrogen and progesterone in mid-luteal phase
inhibit the secretion of FSH and LH (by negative feedback effect).
• Low levels of gonadal hormones (during menstruation phase)
increase the secretion of both FSH and LH.
• The feedback effect of ovarian hormones is brought about by its
action either directly on anterior pituitary or through the
hypothalamus .
 Regulation of gonadotropins cont’
• Clomiphene induces ovulation by acting on hypothalamus and
thereby promotes LH release from anterior pituitary.
• Oral contraceptives contain high concentration of oestrogen and
progesterone. These drugs inhibit gonadotropin release by negative
feedback effect and prevent ovulation.
2. Human chorionic gonadotropin (HCG): secreted by
syncytiotrophoblasts during early pregnancy (12–16 weeks of
gestation). Like LH, HCG also maintains the functional state of corpus
luteum and thus elevates gonadal hormones resulting in inhibition of
gonadotropin release.
3. Prolactin. It is a mammotropic hormone secreted from anterior
pituitary during lactation. It inhibits GnRH release and thus lowers
the basal secretion of FSH and LH (cause for lactation amenorrhoea).
4. Activin. It is structurally quite similar to inhibin (secreted from ovary).
It is synthesized in the cells of the anterior pituitary. It stimulates the
synthesis and release of FSH by autocrine and paracrine actions.
1. Hypogonadism (hyposecretion of ovarian hormones) means
Ab n o rm aliti e s o f o var ian fu n c tio n s

less than normal secretions by the ovaries. It occurs when

the ovaries are poorly developed or absent since birth or
genetically become abnormal and non-functional.
Hypogonadism results in female eunuchoidism.
2. Ovariectomy. When ovaries are removed surgically in a
sexually mature female, it leads to following effects:
i. Atrophy of genital apparatus (i.e. uterus, vagina and external
genitalia)
ii. Stoppage of menstruation.
iii. Vasomotor changes, such as flushing of skin of face, neck
and chest (hot flushes)
iv. Emotional disturbances, such as irritability and depression.
Breast changes. Breasts may enlarge or get atrophied.
 Abnormalities of ovarian functions cont’
3. Hypersecretion by the ovaries. The ovarian
secretions are well regulated by hypothalamo-
hypophyseal ovarian axis. Hence extreme
hypersecretion by the ovaries is a rare condition. If
it occurs in:
• Pre-pubertal stage then precocious puberty results.
• Post-menopausal stage, then hypertrophy of the
endometrium and irregular bleeding are the
common features.
 4. McCune – Albert syndrome

• is a genetic defect in which somatic mutation occurs

after initial cell division in the embryo that leads to
activation of certain cells, but not others.
• This condition is associated with multiple endocrinal
abnormalities including precocious puberty,
amenorrhea and galactorrhea.
• Menstrual symptoms are the unpleasant symptoms with
AB N OR M A L M ENS TR UA TIO N

discomfort, which appear in many women during

menstruation. These symptoms are due to hormonal
withdrawal, leading to cramps in uterine muscle before or
during menstruation.
Common Menstrual Symptoms
1. Abdominal pain
2. Dysmenorrhea (menstrual pain)
3. Headache
4. Occasional nausea and vomiting
5. Irritability
6. Depression
7. Migraine (neurological disorder, characterized by intense
headache causing disability).
 Anovulatory cycle’

• means menstrual cycles occur at normal intervals,

but ovulation does not occur. Anovulatory cycles are
the normal entity upto 1–2 years after the
menarche and few years before menopause. An
anovulatory cycle in the fertile period of
womanhood is the main cause of female infertility.
 Amenorrhoea

• The term amenorrhoea refers to absence of menstrual

bleeding or periods. It is of two types:
• Primary amenorrhoea means menstrual bleeding has
never occurred and this condition is because of failure of
sexual maturation.
• Secondary amenorrhoea means cessation of menstrual
cycles in a woman who previously has normal and regular
cycles. Pregnancy is the most common cause of secondary
amenorrhoea.
• Other conditions which result in secondary amenorrhoea
are: emotional disturbances, environmental changes,
hypothalamic and pituitary disorders and certain systemic
diseases.
 PREMENSTRUAL SYNDROME (PMS)
• is the symptom of stress that appears before the onset of
menstruation. It is also called premenstrual stress syndrome,
premenstrual stress or premenstrual tension. It lasts for about 4 to 5
days prior to menstruation. Symptoms appear due to salt and water
retention caused by estrogen. Common Features:
1. Mood swings
2. Anxiety
3. Irritability
4. Emotional instability
5. Headache
6. Depression
7. Constipation
8. Abdominal cramping 9. Bloating (abdominal swelling).
10. Heaviness
11. Lack of concentration
 ABNORMAL MENSTRUATION

1. Hypomenorrhea: Decreased menstrual bleeding (Scanty

menstruation)
2. Menorrhagia: Excess menstrual bleeding (refers to an
abnormally profuse bleeding during normal regular
cycle)
3. Oligomenorrhea: Decreased frequency of menstrual
bleeding
4. Polymenorrhea: Increased frequency of menstruation
5. Dysmenorrhea: Menstruation with pain
6. Metrorrhagia: Uterine bleeding in between
menstruations (occurrence of uterine bleeding in
between the periods)
 FEM ALE SEXUAL ACT

• Is similar to male sexual act is reflexogenic and

involves psychological and physical components.
The three phases of female sexual act are:
a. Sexual excitement,
b. Orgasm
c. Resolution.
• is also called phase of female erection and lubrication. It
I. Phase of sexual excitement

corresponds to erection of penis in males. This phase is brought

about by integrity of the reflex arc, which comprises following
components:
1. Sexual stimulation. Sexual stimulation in females like that of
males has two components, psychological and physical.
• Psychological stimulation. The sexual desire in females is
aroused by erotic thoughts, which originate from the cerebral
cortex and limbic system (amygdala).
• The sexual desire is believed to be increased at the time of
ovulation (may be because of high levels of oestrogen).
• It is also believed that sexual desire in female is produced partly
by oestrogen.
 1. Sexual stimulation cont’
• Physical component of the sexual stimulation
consists of sexual sensations aroused from
massaging/irritation of external genitalia (vulva,
clitoris, labia minora and labia majora) and perineal
region.
• Clitoris is highly sensitive and is responsible for
initiation of sexual sensations.
• Massaging of the breasts and even kissing enforce
the sexual sensations.
 I. Phase of sexual excitement
2. Afferents to the integrating centres. The sensory signals are
transmitted via pudendal nerve to spinal cord. The impulses are then
transmitted to the cerebral cortex and also to the integrating centres
for the local reflex responses.
3. Integrating centres. The local reflexes are integrated in sacral
segments (S2, S3 and S4) and lumbar segments (L1 and L2) of the
spinal cord. These integrating centres are also influenced by the
psychological components.
4. Efferent pathway. The parasympathetic signals for female erection
and lubrication travel by nervi erigentes from sacral plexus to the
arteries of external genitalia, and Bartholin glands and mucosal
epithelial cells of vagina.
5. Response. During sexual intercourse, the erectile tissue (located
around introitus and clitoris) is activated by parasympathetic
impulses producing:
 5. Response cont’
i. Increase in blood flow and accumulation of blood in erectile tissue
resulting in an increase in the size of external genitalia, and vaginal
congestion. Congestion of vagina occurs due to transudation of fluid
from the vaginal epithelium,
ii. Vaginal lubrication facilitates the penile insertion. Further vaginal
congestion leads to tightening of the vaginal opening around the
penis.
iii. Stimulation also results in copious secretion from the Bartholin
glands (situated beneath labia minora) and mucous cells in vagina.
These secretions further lubricate vagina and help in producing
massaging effect on penis.
iv. With increasing excitement, blood flow further increases resulting in
deepening of colour of labia majora. Along with local response,
systemic effects (as increase in heart rate, respiratory rate and blood
pressure) and in general increase in the muscle tone also occur.
 II. Orgasm
• results when intensity of sexual stimulation reaches its
peak. It is analogous to emission and ejaculation in males.
• During orgasm, there occurs rhythmic contractions of
peroneal muscles, uterus and vagina, and dilatation of the
cervical canal.
• The intense sexual sensation perceived during orgasm is
called climax. This stage lasts for about 15–30 s.
• It has been observed that in lower animals oxytocin
released from the posterior pituitary via amygdala (limbic
system–hypothalamus–posterior pituitary stimulation) is
responsible for the uterine contractions.
 III. Resolution phase

• Orgasm is immediately followed by the resolution

phase.
• This phase is characterized by a sense of satisfaction
followed by relaxed state of mental peacefulness
called resolution.
• The heart rate, blood pressure, respiration and all
other parameters come to their normal level and
there occurs relaxation of the muscles.
 Note

• Dyspareunia refers to recurrent / presistant genital

pain before, during (most common) or after sexual
intercourse.
• This problem is more common in females than
males, the more of physical or psychogenic
problem.