GONADAL FUNCTION

Expected learning outcomes

review anatomy & secretions of male/female
gonads;
evaluate & correlate mechanisms & actions of
male/female hormones;
describe & critique causes & symptoms of hypo-
&hyper-secretions of gonads; and
correlate laboratory assessment and possible
treatment.
Sexual differentiation
REGULATION OF
GONADS
The male
Sexual differentiation & Development
of normal male phenotype
Differentiation of bipotential gonad
primodia into the testes
development of the internal reproductive
tract
development of the external
Male Reproductive tract
Testicular functions
Production of sperm
Production of reproductive steroid
hormones
spermatogenesis
hormonogenesis
 Tanner staging of genital and pubic hair
development in males
Stages of genital devt Stages of pubic hair devt
Prepubertal Lanugo-type hair (prepubertal)
Enlargement of the scrotum and Dark terminal hair at the base of
testes the penis
Increased length of the penis, Darker terminal hair spreading
further enlargement of the testes over the junction of pubes

Enlargement of the testes, Terminal hair covering pubic

scrotum, and penis with growth region, no spread to mesial thighs
of glans; darkening of scrotal
skin
Mature genitalia Mature stage with horizontal
distribution of terminal hair to
inner thighs
DISORDERS OF SEXUAL
DEVELOPMENT AND
TESTICULAR
HYPOFUNCTION
HYPERGONADOTROPIC
HYPOGONADISM
Group of disorders characterized by low
testosterone, elevated FSH or LH, &
impaired sperm production
A. Klinefelter’s syndrome
Caused by the
presence of an extra
chromosome
Gynecomastia is
common
Gynecomastia
• LH & FSH= high
• Reduced bone
density
• Breast cancer
B. Testicular feminization
syndrome
Most severe form Fully developed
of androgen breasts, female
resistance distribution of fat &
hair
Lack of androgen
No response to
Testicles exogenous
undescended testosterone
Reared as girls
Cryptorchidism
C. 5α-reductase deficiency
Rare cause of androgen insensitivity
resulting to XY males
There is reduced DHT (5α-dihydrotestosterone)
Development is female phenotype until
puberty when Wolffian ducts virilize in
response to testosterone
No female internal genitalia; male
genitalia are well developed
D. MYOTONIC DYSTROPHY
There is primary hypogonadism, frontal
balding, DM, muscle weakness, atrophy,
& dystonia

Testicular failure occurs at the 20s or 30s

Primary hypogonadism (oligozoospermia,
infertility)
E. TESTICULAR INJURY &
INFECTION
Causes:
Post-pubertal mumps
Viral orchitis & HIV infection
Radiation and chemotherapy
F. SERTOLI CELL-ONLY
SYNDROME
Characterized by lack of germ cell
Men affected have small testes, high FSH
levels, azoospermia, normal testosterone
Varicocele is an enlargement
of the veins within
the loose bag of
skin that holds the
testicles (scrotum).
is similar to a
varicose vein that
can occur in your
leg.
HYPOGONADOTROPIC
HYPOGONADISM
Hallmark is the occurrence of low
testosterone with low or inappropriately
normal FSH or LH levels
A. KALLMANN’S SYNDROME
Impaired secretion of GnRH
A result of an inherited , x-linked recessive trait
that manifests as hypogonadism during puberty
Occurs in 1:10,000 males
Certain men have red-green color blindness,
congenital blindness, or cerebellar dysfunction
B. hyperprolactinemia
Can be drug induced or caused by tumor
C. DM 2
Occurs in at least 25 to 50% of men
Low free or total testosterone; low LH
Insulin seems to be important for LH
release
There is high C-reactive proteins
D. Age
Testosterone decreases at about 110
ng/dL every decade of life
E. Pituitary disease
As a result of tumor, surgical-or
radiation-induced trauma, vascular injury,
autoimmune hypophysis, or granulomatous
or metastatic disease.
F. Opioid use
Prolonged use or continuous use of
narcotics is linked to severe
hypogonadotropic hypogonadism.
G. Obstructive sleep apnea
Can be due to hypoxemia and sleep
deprivation
Obesity
DIAGNOSIS OF
HYPOGONADISM
Testosteronemeasurement
Pituitary MRI
Testosterone replacement
Administered only to a man who is
hypogonadal
Complications include: acne,
polycythemia, prostate enlargement,
possible growth-promoting effect on
undiagnosed prostate cancer, worsening
of obstructive sleep apnea, peripheral
edema & gynecomastia
Monitoring of testosterone
replacement therapy
PSA
Hematocrit
Lipid levels

Frequency of checking: 3 to 6 months;

then yearly
FEMALE

In the absence of Y chromosome, fetus starts to develop

female characteristics at about 12 weeks.
Proliferation of fetal germ cells produces several
millions of oocytes.
By late fetal life, all germ cells are degenerated
and more oocytes can be produced.
These oocytes decline in number throughout the
rest of intrauterine development and childhood.
The inability to replenish them explains the limit
of women’s reproductive life.
Female Reproductive System
 Ovarian Sex hormones

Estrogen
Progesterone
ovaries
A. ESTROGEN
Estradiol- principal ovarian estrogen

Estrone & estriol- primarily metabolites

of intraovarian & extraglandular
secretions
Effect of estrogen
Promote breast, uterine, vaginal
development
Effect on skin, vascular smooth muscles,
bone cells, & CNS
B. PROGESTERONE
Induces the secretory activity of those
endometrial glands that have been primed
by estrogen
Readying endometrium for embryo
implantation, thickening of cervical
mucosa, reduction of contractions,
thermogenic effect
C. ANDROGENS
Ovaries produce androstenedione,
dehydroandrostenedione, testosterone, 5α-
dihydrotestosterone (DHT)
Levels continue to increase in advanced
age
D. other ovarian hormones
Inhibins A & B : inhibit FSH production

Activin: enhances FSH secretion &

induces steroidogenesis

Folliculostatin,
relaxin: follicle regulatory
protein,oocyte maturation factor, meiosis-
inducing substance
Female Reproductive System
THE MENSTRUAL
CYCLE
Ovarian: Follicular phase
begins with onset of menses
ends on the day of LH surge
Ovarian: Luteal phase
startwith extrusion of ovum 36 hrs after
LH surge
Formation of corpus luteum
 secretion of progesterone to prepare for
implantation
 ends with menstrual bleeding ( 3-5 days)
Female Reproductive System

Luteal (post-ovulatory or secretory) phase

Follicular stage
(pre-ovulation)
 Female Reproductive
System
FSH & LH regulate control of estrogen and
progesterone.
Estrogen and progesterone control the FSH &
LH.
Pubertal development in female
Thelarche (breast development) = earliest
sign
Development of pubic hair
Menarche ( 2 to 3 years after onset of
puberty)
 Tanner staging of breast and pubic hair devt in females
Stages if breast development Stages of pubic hair
development
prepubertal Lanugo-type hair (prepubertal)
Elevation of breast bud and papilla, Dark terminal hair on labia
areolar enlargement majora
elevation of breast tissue and papilla Terminal hair covering labia
majora and spreading to Mons
pubis
Elevation of areola and papilla in Terminal hair fully covering
secondary mound above the level of the labia majora and mons
the breast pubis
Mature stage: recession of areola Terminal hair covering the
into the breast with projection of labia majora, mons pubis, and
papilla only inner thighs
PLACENTAL HORMONES
Pregnancy
 hCG produced by
placenta
 reaches a peak at
about 13 weeks and
then falls.
Urine/plasma hCG
when positive at 1-2
weeks after first
missed menstrual
period commonly
confirms pregnancy
 {Estriol}

Prolactin ------------------------------------for milk production; inhibited

while estrogen is high during gestation . Levels fall postpartum
until it reaches non pregnant level in 2-3 months .
COMPLICATIONS OF
PREGNANCY
GestationalDM
Ectopic pregnancy
Hyperemesis Gravidarum
Preeclampsia
Eclampsia
HELLP syndrome
Graves disease
Hyperemesis Gravidarum
Severe form of nausea & vomiting in
pregnancy
Nausea & vomiting is accompanied by
ketosis & weight loss = acid-base
imbalances, electrolyte imbalances,
nutritional deficits, death
Preeclampsia
Characterized by hypertension and
proteinuria after the 20th week of gestation
Only tx: delivery
Eclampsia
Mother experiences grand mal seizures or
falls into coma
Can lead into intracranial hemorrhage
HELLP syndrome
Means hemolysis, elevated liver enzymes, low
platelet with preeclampsia)
Presence of thrombocytopenia & disseminated
intravascular coagulation (DIC)
Generally occurs between 27 th & 36th weeks,
but can also occurs after delivery
Only tx: delivery
Graves disease
Earlierin pregnancy: fetus is dependent
on mother’s supply of thyroid hormones.
Thus if mother has graves disease, effects
include: preterm delivery, fetal death,
reduced IQ
On 3rd trimester of pregnancy, fetus
produces own thyroid hormones

If mother has graves disease when she

becomes pregnant, her anti-thyroid
antibodies will cross the placenta- leading
to fetal hyperthyroidism
DETECTION OF FETAL
ABNORMALITIES
Amniotic fluid
Provides an environment in which fetus
can move, acts as cushion against possible
injuries, maintains constant temperature
for the fetus
Transports nutrients & electrolytes into
the fetal circulation
Why amniotic fluid volume varies?
Fetus swallows, urinates into the fluid &
secretes fluids through its lungs
Normally fetus does not defecate into
amniotic fluid but when stressed, it may
pass stool called meconium

meconium has a large conc of bile pigment

( thus colored amniotic fluid green)
A. Neural tube defects
Include:
Life threatening a)Meningomyelocele or spina
Failure of neural bifida: bottom end of neural
tube fails to fuse
tube to fuse b)Encephalocele : sac
Correlate with containing brain &
folic acid def in membranes that protrudes
mother during thru an abnormal opening in
the skull
pregnancy
c) anencephaly: lack of parts
show high AFP
of the brain & skull
B. Down syndrome
 trisomy 21
there is low AFP, unconjugated estriol,
and high hCG and inhibin A
concentrations measured between 15 to 20
week’s gestation
C. Hemolytic Disease of the
Newborn
Fetomaternal blood group
incompatibility: shows high amniotic
fluids concentrations of bilirubin in
conjunction with maternal antibodies.
Result is read using Liley chart (relating
optical density of amniotic fluid at 450
nm
D. Respiratory Distress Syndrome
Also called Hyaline membrane disease
Occurs in babies born before 37 weeks
Babies lack pulmonary surfactant
Lab diagnosis of fetal abnormalities
AFP testing
Screening for chromosomal abnormalities
Fetal lung maturity testing
a. Lecithin/sphingomyelin ratio
b. Phosphatidyl glycerol
c. Fluorescent polarization test
Lecithin is a major component of airway
surfactant
Sphingomyelin is a non-lung compound
that serves as a good internal standard
Infants with mature lungs: L/S ratio is 2
or more
In Fetal lung maturity: L/S ratio is less
than 2
NOW steroids can induce surfactant
synthesis
HYPOGONADOTROPIC
HYPONGONADISM
Low sex steroid=common cause of
secondary amenorrhea
Other causes: weight loss due to anorexia
nervosa; intense physical exercise
( runner’s amenorrhea); prolactinoma
HYPERGONADOTROPIC
HYPOGONADISM
MENOPAUSE
menopause
Time of permanent cessation of
menstruation.
Occurs when all follicles have atrophied.
Plasma estrogen fall
DISORDERS OF FEMALE
GONADAL FUNCTION
Amenorrhea [ primary: woman who has
never menstruated by age of 16;
secondary: has at least one menstruation
followed by absence of menses for a
minimum of 3-6 months]
Oligomenorrhea: infrequent irregular
menstruation, with cycle lengths in excess
of 35 to 40 days

Menorrhagia: uterine bleeding of more

than 7 days
Polycystic ovary syndrome
The most common disorder can present in
many ways: infertility, hirsutism, chronic
anovilation, glucose intolerance,
dyslipidemia, hypertension
Hirsutism
Abnormal, abundant, androgen-sensitive
terminal hair growth in areas in which
terminal hair follicles are not normally
found in women
Estrogen replacement therapy
Increased incidence of breast cancer &
venous clot formation
Other disorders of reproductive
organs
Precocious puberty: appearance of
secondary sexual characteristics before
the age of 8 and can be
a. true (central)= caused by cerebral
tumors, infection, trauma
b. psuedoprecocious= puberty caused by
adrenal or gonadal tumor
Precocious puberty
Female pseudohermaphroditism
individuals with XX chromosomes but
male genitalia characteristics and
virilization
 male pseudohermaphroditism

individuals with XY
chomosomes and possess
two testes but female
external genitalia
True hermaphroditism= individuals with both
testicular and ovarian tissue
*Males and females both have male and female
sex hormones, but in varying levels.
Gonadal assessment
Gonadotropin-releasing
hormone test
Human hCG stimulation test