Bleeding Conditions in

Women and Adolescents

Hilary Morgan, CNM, PhD
Nancy Robinson, CNM, MSN, MPH
Jacksonville University
Menstrual Cycle

 Regular cyclic occurrence of menstrual

bleeding that takes place with ovulation
and absence of conception
 Interplay between ovaries,
hypothalamus, anterior pituitary and
uterine endometrium
Menstrual cycle
Physiology
 Hypothalamus produces and secretes
hormones and releasing factors
(Gonadotropin releasing hormone) that act
directly on pituitary gland. It continuously
monitors hormone levels in bloodstream
 In response, the pituitary gland releases
hormones to stimulate ovaries (FSH, LH)
FSH & LH
– Follicle stimulating hormone (FSH)
stimulates ovarian production of estrogen
and maturation of ova and follicles
– Luteinizing hormone (LH) induces mature
ovum to burst from follicle and stimulate
development of corpus luteum (portion of
follicle that remains after release of ova).
– Corpus luteum (CL) responsible for
production of progesterone.
Endometrial Menstrual Cycle

 Proliferative phase
 Secretory phase
 Menstrual phase
Proliferative Phase
 Pituitary gland increases production of FSH, stimulating
follicles to mature and produce estrogen
 Estrogen, in turn, causes endometrium to thicken
 When ovarian estrogen level reaches peak, pituitary
inhibits release of FSH and stimulates LH production.
 Ovulation occurs due to LH surge approximately 14
days before start of next cycle
 Estrogen also changes composition of cervical mucous
secretion (more alkaline) making conception more likely
Secretory Phase
 Pituitary continues LH production leading to
development of corpus luteum from ruptured follicle
 CL produces progesterone which inhibits
production of cervical mucous
 Estrogen and Progesterone cause endometrium to
thicken and engorge in preparation for implantation
 Progesterone causes increase in temperature with
ovulation
Secretory Phase

 If implantation doesn’t occur, pituitary

gland (in response to high E&P levels,
halts production of LH and FSH).
 CL can no longer produce progesterone
and disintegrates
 Production of estrogen and
progesterone decreases
Menstrual Phase
 Estrogen & Progesterone drop off triggers
endometrium sloughing
 Discharge of thickened inner layer of
endometrium
 As E & P continue to fall, hypothalamus
responds by stimulating pituitary to
release FSH
 Cycle repeats itself
Menstrual cycle
 Ovulation marks transition from follicular
to luteal phase
 First day of menstrual flow is considered
day one of cycle
 Luteal phase is most consistent at 14
days; follicular phase usually 14-21
 Cyclic variation usually occurs during
follicular phase
Menstrual Cycle
 Average cycle is approximately 28-35 days but
normal range is from 21 to 42 days (3-6 weeks)
 Normal duration is 2-7 days (average 3-5 days)
 Menstrual flow averages 10-35 ml
 Normal pad or tampon holds 5 ml; 2-7 saturated pads
normal for full cycle
Menstrual Cycle
 Mostly regular between ages 20-40.
 More variation in first 5-7 years after
menarche and last 10 years prior to
menopause.
 Most girls will have regular cycles within 1
year of menarche.
 Cycles do become shorter (length in days)
over time
Menarche

 Defined as first menstrual cycle in

human female
 Central event in female puberty
 Beginning of fertility period in female
lifespan
Menarche

 Average age of menarche in US is 12.5

years
 Less than 10% of girls begin menarche
before age 11
 90% of girls reach menarche before age
13.75
Physiology of Menarche
 Puberty signs in young girls begin
approximately age 8-13
 Thelarche (breast budding), adrenarch
(development of pubic/axillary hair), growth
spurt (usually occurs 0.5 year before
menses), menses
 95% of adult height is achieved by menarche
 What triggers menarche?
Onset of secondary sex
characteristics:
 Breast development (Thelarche) 10.5 yr
 Hair Development (Andrenarche) 11.0 yr
 Growth (peak height velocity) 11.4 yr
 Menstruation (Menarche) 12.8 yr
Estrogen

 Leads to breast enlargement

 Growth of body hair
 Muscle development
 Wider hips
 Rounder face
 Change in fat distribution
 Vaginal secretions
What triggers Menarche?
 Interrelated factors:
– Genetic (how old was mom’s menarche)
– Ethnic/racial
– Geography
– Environmental
– Nutrition, body fat and exercise
 During most of the 20th century age at
menarche has been falling by about 3 months
per decade
What triggers Menarche?
 Onset of puberty occurs after reactivation of the
hypothalamic Gonadotropin Releasing Hormone
(GnRH) secretory system.

 The GnRH secretory network initially develops and is

temporarily active during fetal and neonatal life and
early infancy, i.e. during the first 6 months of life, the
so-called 'mini-puberty'.

 These early periods of GnRH activation may be

important for masculinisation or feminisation of the
brain
Health implications of early or late
menarche

Early Menache Late Menache

•Abdominal type obesity •Osteoporosis
•Insulin resistance
•Glucose intolerance •Adolescent depression
•Cardiovascular risk •Social anxiety symptoms
•Coronary heart disease
• Increased bone mineral density
• Increased cancer mortality
•Related to anxiety symptoms,
depression, premature intercourse and
violent behavior.
Precocious Puberty

 Onset of secondary sex characteristics

before age 8 in girls (9 in boys)
 2-2.5 SD below norm
Amenorrhea
Case study

 Lori is a 16 yo G0 brought in by her

mom to see you
 She has never had a period
 She asks if this is normal.

 What are your first thoughts?

What is amenorrhea?
When is amenorrhea normal?
Amenorrhea
 Physiologic- normal absence of menstruation before
menarche, during pregnancy and lactation and after
menopause
 Pathologic – absence of menses for at least three
months (not related to any of above)
– Congenital abnormalities
– CNS lesions
– Systemic condition
– Ovarian disturbances
– Uterine trauma
What is the mechanism for
physiologic amenorrhea?
What is the difference between
primary and secondary
amenorrhea?

What are the common causes of

primary? Secondary?
 Primary vs Secondary
 Primary-
– Absence of menses at age 15 in presence of normal
growth and secondary sexual characteristics
– Or absence of menses at age 13 and complete
absence of secondary sexual characteristics
• More likely due to genetic, anatomical abnormality
 Secondary-
– 3 month absence of menses in girls or women who
previously had regular cycles or 6 months in girls or
women who had irregular menses.
Primary Amenorrhea

 Definition
 Etiology
 History and Physical Examination
 Work up
 Management
Definition

 Amenorrhea is absence of menses.

Primary occurs when menses hasn’t
started by age 15
 Usually other signs of puberty have
occurred but not always
 Incidence < 0.1%
Etiology
 Most due to fetal errors involving gonads,
mullerian and wolffian systems or urogenital
sinus (external genitalia)
(absence/abnormality of reproductive organs)
 Genetic abnormalities account for 50% cases
(and most of those are absent secondary sex
characteristics).
 Hypothalamic or pituitary dysfunction (non
genetic causes)
What would you look for in her
history?
History
 Family history genetic abnormalities
 Notations at birth related to abnormalities in
external genitalia
 Growth and development (secondary sex
characteristics)
 Nutrition
 Systemic disease
 Hospitalizations and or surgeries
 Emotional difficulties
What would you look for in her
physical exam?
 Physical exam
 Height, weight
 Turner syndrome features (low hairline, webbed neck, widely
spaced nipples
 Appearance of secondary sex characteristics
– Breast development, galactorrhea
– Hair distribution (pubic, axillary, bitemporal baldness)
– Body habitus
– Pelvic exam
• Non patent vagina
• Infantile external genitalia
Physical exam
 Absence of menarche with normal appearance
and progression of secondary sex characteristics is
suggestive of abnormality of
– Mullerian tract (congenital absence of uterus)
– Hypothalamus (stress)
– Anterior pituitary (tumor)
– Ovaries (premature failure)
 Absence of menarche with total absence of
secondary sex characteristics suggests genetic
basis for amenorrhea
What diagnostic tests do you
want to order?
Work up

 HcG
 Serum prolactin
 TSH
 FSH
 Pelvic Ultrasound
 Genetic karyotype
What is your management?
Progestin Withdrawal

 Progesterone withdrawal test- Provera

10mg daily x 7-10 days. Withdrawal
bleeding will occur within 2-10 days
 Withdrawal bleed indicates intact
hypthalamic-pituitary-ovarian axis as
well as patency of reproductive tract
Management

 Surgical correction
 Weight gain, stress reduction
 Hormone replacement
– Develop secondary sex characteristics
– Allow normal sexual function
– Prevent development of osteoporosis
Case study

 Linda is a 42 yo G2P2
 VSS, 65 inches tall, BMI 24.6
 Presents to FNP for amenorrhea x 5
months after cessation of Ocs

 She wants to know what is going on

What are your immediate
considerations for Linda?

What type of amenorrhea is this?

Secondary Amenorrhea

 Defined as cessation of menstruation of

at least 3 months once menarche has
occurred
Etiology/Patho
 Congenital abnormalities less common
 Pregnancy, Menopause must be considered
 Polycystic ovarian syndrome
 Extremes in body habitus (under or over weight)
 Excessive exercising
 Pituitary tumors
 Thyroid disorders
 Premature ovarian failure
Etiology

 Medications such as OCs and

Depoprovera
 Surgery such as D&C
– Asherman’s syndrome (adhesions)
What history do you need to
obtain?
History
 Menstrual hx
 Obstetrical hx
 Surgery hx
 Systemic diseases
 Nutritional status
 CNS involvement
 Drugs
 Extrinsic factors such as recent stress, weight gain,
illness
 Hormone deficiency symptoms
What will you look for on the
PE?
Physical exam
 Same as with primary amenorhea
 Observe for signs of pregnancy
 Estrogen deficiency
 Galactorrhea
 Virilization
What diagnostics will you order?
Work up
 HcG
 FSH
 TSH
 Prolactin
 Androgen studies
– LH (PCOS)
– Testosterone, androstendione, DHEA
 Progesterone withdrawal
 US
 HSG
What is your management plan?
Management
 Similar to management for primary amenorrhea
 Options depend on patient’s desire for pregnancy
– OCs to regulate menses
– If desire pregnancy, progesterone withdrawal
every 6-8 weeks, temperature/ovulation charts
 Stress/behavioral changes
 Meds for thyroid, prolactin, PCOS
Menstrual Disorders
Menstrual Disorders

 Abnormal Uterine Bleeding

 Dysmenorrhea
 Premenstrual Syndrome
Case study

 Lorraine is 45 yo G3P3
 Menses q 28 days
 For last 3 months, she is bleeding q 12-
15 days
 What are you first thoughts?
Abnormal Uterine Bleeding

 Dysfunctional uterine bleeding- term no

longer used
 Prepubertal bleeding
 Perimenarcheal bleeding
 Reproductive Age bleeding
 Peri/Post Menopausal
Abnormal Uterine Bleeding

 Accounts for 20% of GYN visits; 25%

GYN surgeries
 Refers to any uterine bleeding that is
irregular in amount, duration or timing
 How is irregular in amount, duration or
timing defined?
Definitions
 Amenorrhea- absence of menses > 90 days
 Menorrhagia (or hypermenorrhea)- excessive bleeding at
time of menses, either in number of days, amount of blood
or both; occurs during a regular cycle
 Metrorrhagia- menstrual bleeding at irregular intervals
usually between cycles
 Menometrorrhagia- prolongation of menstrual flow
associated with irregular intermenstrual bleeding
 Hypomenorrhea- decrease in amount of menstrual flow
 Oligomenorhea- infrequent, irregular episodes of bleeding
usually occurring at intervals of more than 35 days
 AUB
 P-polyp
 A-adenomyosis
 L-leiomyoma
 M-malignancy and hyperplasia
 C-coagulopathy
 O-ovulatory dysfunction
 E-endometrial
 I-iatrogenic
 N-not yet classified
Polyps

 May be endometrial or endocervical

 Epithelial proliferations composed of
vascular, glandular, fibromuscular or
connective tissue
 Typically benign
Polyps
Adenomyosis
 Endometrial tissue that has penetrated
the myometrial layer
 Not as well identified on U/S
 Often diagnosed histologically after
hysterectomy
Leiomyoma

 Benign fibromuscular tumors

 70-80% prevalence
 May be asymptomatic
 May present as one or numerous
varying in size and location
 Submucosal lesions most
likely cause of AUB
Leiomyoma
Malignancy and Hyperplasia

 Will be discussed under GYN cancers

Coagulation Disorders

 Heavy menstrual bleeding

(menorrhagia)
 13% due to von Willebrand disease
Ovulatory Dysfunction
 Characterized by unpredictable timing of bleeding and
variable amount of flow
 Usually due to a loss of coordinated cyclic hormonal
changes and excludes organic lesions; anovulatory
cycles
 Can range from amenorrhea to extremely heavy,
unpredictable heavy menstrual bleeding
 PCOS, hypothyroid, hyperprolactinemia, mental stress,
obesity, anorexia, extreme exercise, weight loss
 Tricyclic anti-depressants, steroids
Endometrial

 Usually predictable and cyclic

 Deficiencies of local production of
vasoconstrictors
 Endometrial infection/inflammation
Endometritis
Endometriosis
Iatrogenic

 IUD
 Pharmacologic agents
 Break through bleeding (BTB) on OCs
Not yet classified

 Anything else!
 Pregnancy- normal 1st trimester
spotting, spontaneous ab, ectopic,
molar pregnancy, pp endometritis
 UTIs
 GI- hemorrhoids, fissues, IBS
 Malnutrition (over or under weight)
Does it matter if your patient
presenting with AUB is 21 vs 41vs
61 years of age?

What are your differentials for

someone 21?
What are your differentials for
someone 41?
What are your differentials for
someone 61?
AUB- age matters!
 Menarche to age 20 – due mostly to
anovulatory cycles
 Ages 20-40- Commonly due to pregnancy,
PID, IUDs, OCs, neoplasms, thyroid
disease, endometriosis and adenomyosis.
Anovulation accounts for <20% cases
 Age 40 and older- anovulation likely cause
but neoplasms must be R/O
What does it mean to say a cycle
is anovulatory?
Anovulatory Cycles

 Cycles characterized by varying

degrees of menstrual intervals
 Absence of ovulation
 Absence of luteal phase

 What hormone does this impact?

Anovulatory Cycles

 Anovulatory cycles lead to excessive

estrogen stimulation on endometrium as
progesterone not released from CL to
counteract estrogen and coordinate
shedding
 Hyperplasia results leading to irregular
menstrual shedding
Ovulatory AUB

 Can result in midcycle bleeding due to

reduced estrogen levels at ovulation.
 Luteal phase insufficiency are due to
inadequate progesterone production
which results in early menstrual
shedding
What H&P will you perform on
Lorraine?
H&P
 Patient Age
 Last menstrual cycle
 Evaluate bleeding history including pattern,
volume, duration
 Medications
 Recent medical issues
 Complete examination noting signs of hirsutism,
obesity
 Pelvic exam
Pelvic exam
 External genitalia for lesions, atrophy
 Vaginal exam for lesions, atrophy, discharge,
bleeding, masses, fissures
 Cervix- look for lesions, infection, polyp
 Bimanual –note size, shape, contour, masses
 Rectal exam for hemorrhoids, masses,
fissures, occult blood
What diagnostic tests will you
order for Lorraine?
Work up
 Pregnancy test
 Genital cultures
 Cytology
 Vaginal wet mount
 Occult blood
 UA
 CBC/Thyroid/Coag tests
 Prolactin, FSH/LH, PCOS labs
 Endometrial biopsy (if over age 40)
 Biopsy of lesion
 Pelvic ultrasound- to measure endometrial stripe (if
post menopausal) or to r/o fibroids
What is your management plan?
Management
 Hormonal contraceptives/LNG-IUS (Mirena IUD)
 If desire pregnancy, may use provera/clomid to
achieve ovulation
 NSAIDs may be used for benign menorrhagia
(one tablet 3-4 x daily)
 D&C
 Uterine ablation/hysterectomy
 Lysteda-antifibrolytic medication
New Terminology
 Dysmenorrhea
– Cyclic pelvic pain (CPP)
– Cyclic moods
– Physical discomforts
 Dysmenorrhea-Cyclic pelvic pain (CPP)
 Primary vs Secondary
 Management
Dysmenorrhea
 Dysmenorrhea- difficult or painful menstruation
 Primary dysmenorrhea- painful menstruation in absence
of pathology; symptoms usually involve abdominal
cramps, headache, backache, general body aches,
continuous abdominal pain
 Secondary dysmenorrhea involves underlying pathology
acting on pelvic anatomy to cause pain symptoms during
menstrual flow
 80% of teens, early 20s
 10-20% are disabled from pain with half missing work or
school
Dysmenorrhea
 Increase or imbalance in quantity of prostaglandins
present in menstrual fluid of women with
dysmenorrhea
 Excessive amounts of prostaglandins cause uterus
to contract abnormally and reduce uterine blood
flow (ischemia) and oxygenation, giving rise to pain
 Contractions are nonrhythmic, occur at high
frequency (4-5/10min)
 Starts just prior to or with onset of menses and lasts
12-72 hours
What are your differentials?
Differential Diagnosis
 Endometriosis
 PID
 Uterine fibroids
 Adenomyosis
 Pelvic relaxation
 Cervical stenosis
 Interstitial cystitis
 IBS
 UTI
History
 Patient age
 Bleeding pattern
 n&v, diarrhea, back pain, dizziness, HA
during cycle
 Childbirth history
 Dyspareunia
 Progression of severity
 Impact on daily activities
PE & Diagnostics

 Primary dysmenorrhea- likely normal

exam
 Secondary-
– Cervical discharge, pain, bulky uterus
 Diagnostics- none
Management

 R/O pathology
 NSAIDs
 Hormonal Contraceptives
 Tocolytics
 Complementary
Premenstrual Syndrome-
Diagnosis
 Symptoms consistent with PMS
 Consistent occurrence of symptoms only
during luteal phase of menstrual cycle;
symptoms resolve within a few days after
starting menses
 Negative impact of symptoms in women’s
life; impair functioning
 Exclusion of other diagnoses
ACOG Definition
 At least one symptom associated with “economic or
social dysfunction” that occurs during the five days
before the onset of menses and is present in at least
three consecutive menstrual cycles. Symptoms may
be affective (eg, angry outbursts, depression) or
physical (eg, breast pain and bloating)
Premenstrual Syndrome
 Encompasses more than 200 symptoms that present
in some women before start of menstrual flow
 Symptoms behavioral and physical and include
tension, irritability, depression, anxiety, insomnia,
fatigue, headaches, breast tenderness, bloating
(most common)
 85% of women have one or more symptom but only
10% seek treatment
 20-30% have clinically significant symptoms
Etiology of PMS

 Decrease in circulating estrogens prior

to menses causes fluctuation in levels
of neurotransmitters (dopamine,
serotonin receptors) produces PMS
symptoms
 Genetics also thought to play a role
Management of PMS

 Lifestyle:
• Develop consistent sleep schedule
• Decrease caffeine, sodium intake
• Engage in moderate aerobic exercise
• Vitamin B6, E, calcium, magnesium
Pharmaceutical Management
 Analgesics
 Hormonal Contraceptives
 SSRIs
– Prozac/Sarafem (Fluoxetine)-only therapy shown in
controlled trials to be effective
– 20 mg days 14-28 of cycle or through first few days of cycle
– Only when having symptoms
– Continuously
– 60-70% improvement
 Diuretics not shown to help
Take home points

 Age plays a major role in management

of bleeding disorders
 Presence or absence of secondary sex
characteristics help with diagnosis
 Must protect endometrium
 Hormonal contraceptives, IUDs useful
in management of bleeding disorders