Amenorrhea

04/15/22 JEMBERE T(Gynecology for Midwives) 1

 Amenorrhea
• Amenorrhea is the absence of
menstruation
• Primary
– Absence of menses by age 16 with
normal secondary sexual
characteristics
– Absence of menses by age 14
without secondary sexual
development
• Secondary
– Absence of menses for 6 months in
a previously menstruating female
04/15/22 JEMBERE T(Gynecology for Midwives) 2
Events of Puberty
• The larche (breast development)
– Requires estrogen
• Pubarche/adrenarche (pubic hair development)
– Requires androgens
• Menarche
Requires:
– GnRH from the hypothalamus
– FSH and LH from the pituitary
– Estrogen and progesterone from the ovaries
– Normal outflow tract

04/15/22 JEMBERE T(Gynecology for Midwives) 3

Secondary amenorrhea

Not Pathologic:

Pregnancy

Breast feeding,

Hormonal Contraception

Menopause

04/15/22 JEMBERE T(Gynecology for Midwives) 4

Normal Menses Requires

• Outflow tract
• Endometrium
• Hormones estrogen and
progesterone from the ovary
• LH/FSH (anterior pitiutary)
• GNRH (Hypothalmus)
• Inhibitory and stimulatory
functions

04/15/22 JEMBERE T(Gynecology for Midwives) 5

 Etiologies
• Don’t forget PREGNANCY!
– Most common cause of secondary amenorrhea
– Rule out with a urine or serum HCG before proceeding
• Consider each level of the control of the menstrual cycle:
– Hypothalamus
– Pituitary
Involved in endocrine regulation of the menstrual cycle
– Ovary
– Uterus
– Cervix Responds to endocrine cues from the HPG axis

– Vagina
Involved structurally in the outflow of menstrual blood

04/15/22 JEMBERE T(Gynecology for Midwives) 6

Most Common Etiologies of Secondary Amenorrhea

• Pregnancy

• Ovarian disease (40%)

• Hypothalamic dysfunction (35%)

• Pituitary disease (19%)

• Uterine disease (5%)

• Other (1%)

04/15/22 JEMBERE T(Gynecology for Midwives) 7

The Hypothalamic-Pituitary-Ovarian Axis

04/15/22 JEMBERE T(Gynecology for Midwives) 8

http://www.shen-nong.com/eng/images/exam/missedperiods/img_mp1a.gif
Classification of amenorrhea

• Hypothalamic amenorrhea

• Pituitary amenorrhea

• Ovarian amenorrhea

• Uterine amenorrhea

04/15/22 JEMBERE T(Gynecology for Midwives) 9

 Dysfunction of the H-P-O Axis
• Hypothalamic amenorrhea
– Psychological stress   iGnRH secretion
– Anorexia nervosa, weight loss
– Increased exercise levels
 FSH/LH or normal
– Cranial irradiation
– drug-induced amenorrhea
– Space-occupying lesion of CNS

04/15/22 JEMBERE T(Gynecology for Midwives) 10

 Dysfunction of the H-P-O Axis
• Pituitary amenorrhea:
– Hyperprolactinemia
 FSH/ LH secretion
• Prolactinomas account for 20% of secondary
amenorrhea
• Account for 90% of secondary amenorrhea
due to pituitary problems
– Pituitary tumors
• Acromegaly
• Corticotroph adenomas (i.e. Cushing’s
disease)
• Meningioma (of the sella), germinoma, glioma
– Pituitary infarct/pituitary apoplexy
• Sheehan’s syndrome
04/15/22 JEMBERE T(Gynecology for Midwives) 11
 Dysfunction of the H-P-O Axis…
• Ovarian amenorrhea
– Gonadal dysgenesis
– Turner syndrome: low hair
line, web neck, shield chest,
and widely spaced nipples  FSH/ LH secretion
– resistant ovary syndrome
– Premature ovarian failure
– Hyperandrogenism
• Polycystic Ovary
Syndrome (PCOS)
04/15/22 JEMBERE T(Gynecology for Midwives) 12
 Mayer-Rokitansky-Kuster-Hauser Syndrome
(utero-vaginal agenesis)
• 15% of primary amenorrhea
• Normal secondary development &
external female genitalia
• Normal female range testosterone level
• Absent uterus and upper vagina &
normal ovaries
• Karyotype 46-XX
• 15~30% renal, skeletal and middle ear
anomalies
04/15/22 JEMBERE T(Gynecology for Midwives) 13
 Androgen Insensitivity
• Normal breasts but no sexual hair
• Normal looking female external
genitalia
• Absent uterus and upper vagina
• Karyotype 46, XY
• Male range testosterone level
• Treatment : gonadectomy after
puberty

04/15/22 JEMBERE T(Gynecology for Midwives) 14

Dysfunction of the H-P-O Axis…

Typical features of Turner Syndrome

04/15/22 JEMBERE T(Gynecology for Midwives) 15

 A Brief Word About PCOS
• Accounts for 20% of cases of
amenorrhea
• Manifestations include:
– Acne
– Menstrual irregularities
– Obesity
– Premature pubarche, and/or
precocious puberty
Adolescent Polycystic Ovary
• To diagnose, any 2 of 3:
Manifestations of polycystic ovary syndrome In
– Oligomenorrhea/amenorrhea proportion to relative incidence and coincidence
– Signs of androgen excess
– Presence of polycystic ovaries
on ultrasound (≥ 12 follicles)

04/15/22 JEMBERE T(Gynecology for Midwives) 16

Dysfunction of the H-P-O Axis…

• Uterine amenorrhea
– Absence of uterus
– Asherman syndrome
• anatomic abnormalities of
the reproductive tract
– Imperforate Hymen

Imperforate Hymen
04/15/22 JEMBERE T(Gynecology for Midwives) 17
 Asherman’s Syndrome
• Results from acquired scarring of
endometrial lining Hysteroscopic View of
– Secondary to postpartum hemorrhage or Asherman’s Syndrome
endometrial infection, followed by
instrumentation (i.e. D & C)
• Diagnosis suggested by absence of normal
uterine stripe on pelvic ultrasound
• Can confirm diagnosis by
– Absence of withdrawal bleeding after
administration of estrogen, then
progestin for several weeks
– Hysteroscopic evaluation of the
endometrium

JEMBERE T(Gynecology for Midwives)

04/15/22 18
 Diagnosis
• Exclude Pregnancy
• History:
– Recent stress, weight change, new diet or exercise habits,
illness?
– New acne, voice deepening?
– New medications?
• Recent initiation or discontinuation of OCPs
• Danazol/androgenic drugs
• High-dose progestins
• Metoclopramide and antipsychotics
– Can increase serum prolactin  amenorrhea

04/15/22 JEMBERE T(Gynecology for Midwives) 19

Diagnosis
• History:
– Symptoms of hypothalamic-pituitary disease?
• Headaches
• Galactorrhea
• Visual field defects
• Fatigue
• Polyuria, polydipsia
– Symptoms of estrogen deficiency?
• Hot flashes
• Vaginal dryness
• Poor sleep
• Decreased libido
04/15/22 JEMBERE T(Gynecology for Midwives) 20
Diagnosis
– History of obstetrical catastrophe, severe bleeding?
(Possible Sheehan’s Syndrome)
– History of D&C (particularly multiple or after
infection), endometritis? (Possible Asherman’s
Syndrome)

04/15/22 JEMBERE T(Gynecology for Midwives) 21

 Diagnosis
• Physical Exam
 BMI
– BMI > 30 kg/m2 seen in 50% of women with PCOS
– BMI < 18.5 kg/m2 may have functional hypothalamic
amenorrhea
– Signs of systemic illness/cachexia
– Evaluate genital tissue for signs of estrogen deficiency
– Palpate breasts/attempt to express galactorrhea
– Neuro exam for visual field defects

04/15/22 JEMBERE T(Gynecology for Midwives) 22

 Diagnosis
• Laboratory Testing
– Serum prolactin, TSH, FSH (high in primary
ovarian failure)
• Serum prolactin can be increased by stress,
nipple stimulation, or eating
– If signs of hyperandrogenism: testosterone (serum
free and total testosterone)
– If relevant, assess estrogen status
• Serum estradiol (highly variable in early ovarian
failure or recovering hypothalamic amenorrhea)

04/15/22 JEMBERE T(Gynecology for Midwives) 23

Treatment
• Treatment varies depending upon the causes of the
amenorrhea. Treatment options include:
– Dietary changes, including an increase in fat and
calories in order to stimulate estrogen production
– Counseling for eating disorders
– Using stress reduction techniques to help regulate the
period
– Hormonal supplements, like the birth control pill or
hormone replacement therapy.
– Surgery to remove cysts, fibroids or tumors
04/15/22 JEMBERE T(Gynecology for Midwives) 24
 Treatment
• For functional hypothalamic amenorrhea
– Explain need for increased caloric intake and/or
reduced exercise
– Cognitive Behavioral Therapy demonstrated to be
effective in helping women resume ovulatory cycles
in one small study
• For hyperprolactinemia
– Dopamine agonist therapy
• Primary ovarian insufficiency
– Hormone therapy for prevention of bone loss

04/15/22 JEMBERE T(Gynecology for Midwives) 25

Treatment
• Hyperandrogenism/PCOS
– Treatment directed toward symptoms/goals of
patient
• fertility
• prevention of obesity and metabolic defects
– Endometrial protection via resumption of menses,
and if necessary, cyclic or continuous
OCPs/hormonal therapy
• Asherman’s Syndrome
– Hysteroscopiclysis of adhesions
– Long-term estrogen administration to stimulate re-
growth of endometrial tissue

04/15/22 JEMBERE T(Gynecology for Midwives) 26