Absence of menses for ≥3 months (regular cycles) or ≥6 months (irregular cycles) in a previously menstruating woman.
Also known as: secondary amenorrhea, missed menses, absent menses
Overview
Cessation of menstruation for at least 3 consecutive months in a woman with previously regular cycles, or 6 months in a woman with previously irregular cycles.
Epidemiology
Affects ~3-4% of reproductive-age women. Pregnancy is by far the most common cause; pathologic causes include PCOS (most common pathologic), hypothalamic amenorrhea, hyperprolactinemia, thyroid disease, and primary ovarian insufficiency.
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Question 1ReproductiveMedium
A 29-year-old woman has secondary amenorrhea. Pregnancy test is negative. TSH is normal and prolactin is elevated. Which of the following symptoms is most likely associated?
ARecurrent hot flashes
BBilateral galactorrhea
CCoarse facial hirsutism
DAcanthosis nigricans
Reveal answer & full explanation
Correct answer: B — Bilateral galactorrhea
ARecurrent hot flashes
BBilateral galactorrhea✓
CCoarse facial hirsutism
DAcanthosis nigricans
Why Bilateral galactorrhea is correct
Elevated prolactin suppresses GnRH, lowering LH and FSH, which explains the secondary amenorrhea.
Prolactin directly stimulates breast milk production, so galactorrhea is the classic accompanying sign of hyperprolactinemia.
A normal TSH excludes hypothyroidism as the driver, isolating prolactin excess as the cause.
Why the others are wrong
Recurrent hot flashes — point to estrogen deficiency from primary ovarian insufficiency or menopause, not prolactin excess (amenorrhea-cause trap).
Coarse facial hirsutism — reflects androgen excess such as PCOS; prolactin elevation does not virilize.
Acanthosis nigricans — is a cutaneous marker of insulin resistance seen with PCOS-related anovulation; prolactin excess does not produce it.
Question 2ReproductiveMedium
A 22-year-old competitive distance runner presents with absence of menses for the past 5 months; her cycles were previously regular. Over this period she increased her training to 70 miles per week while restricting calories, and her BMI is 17.5 kg/m². She reports no galactorrhea, hot flashes, or hirsutism. A urine pregnancy test is negative. Laboratory studies show low FSH, low LH, and a low estradiol level, with normal TSH and prolactin. Which of the following is the most likely diagnosis?
AFunctional hypothalamic amenorrhea
BAmenorrhea from chronic opioid use
CAutoimmune premature ovarian failure
DAnovulatory polycystic ovary syndrome
Reveal answer & full explanation
Correct answer: A — Functional hypothalamic amenorrhea
AFunctional hypothalamic amenorrhea✓
BAmenorrhea from chronic opioid use
CAutoimmune premature ovarian failure
DAnovulatory polycystic ovary syndrome
Why Functional hypothalamic amenorrhea is correct
Energy deficit from caloric restriction plus high-volume endurance exercise suppresses hypothalamic GnRH pulsatility, lowering FSH and LH and producing hypoestrogenism.
The hallmark biochemical pattern is low/normal FSH, low LH, and low estradiol (hypogonadotropic hypogonadism) in a thin, athletic, or stressed patient with otherwise normal TSH and prolactin.
It is a diagnosis of exclusion; per ACOG/Endocrine Society guidance, first-line management is restoring energy availability (nutrition, reduced training, stress reduction) before hormone therapy.
Why the others are wrong
Anovulatory polycystic ovary syndrome causes chronic anovulatory amenorrhea but presents with hyperandrogenism (hirsutism, acne), normal-to-elevated LH, and often elevated BMI, rather than low FSH/LH and low estradiol in an underweight athlete.
Amenorrhea from chronic opioid use also suppresses GnRH and reproduces the same low FSH, low LH, low estradiol pattern, so the labs cannot separate it; however, no opioid or other medication exposure is reported, while the documented energy deficit (70 miles per week with caloric restriction at a BMI of 17.5 kg/m²) fully accounts for her presentation.
Autoimmune premature ovarian failure (primary ovarian insufficiency under age 40) produces hot flashes and vaginal dryness with HIGH FSH and low estradiol; this patient has low FSH and no hypoestrogenic vasomotor symptoms.
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Thyroid disease — Hypo- or hyperthyroid symptoms; abnormal TSH
Primary ovarian insufficiency — Hot flashes, vaginal dryness <40 yo; elevated FSH on two occasions
Asherman syndrome — Amenorrhea or hypomenorrhea after D&C, endometritis, or uterine surgery; absent withdrawal bleed; hysteroscopy diagnostic
Cushing syndrome / hyperandrogenism (CAH, tumor) — Virilization, central obesity, striae; specific endocrine testing
Diagnostic workup
Diagnostic criteria
Progesterone challenge test (medroxyprogesterone 10 mg × 10 days) can assess estrogen status: bleeding suggests adequate estrogen + patent outflow (anovulation pattern); no bleeding suggests low estrogen OR outflow obstruction OR endometrial unresponsiveness — confirm with estrogen-progestin challenge.
Labs
Pregnancy test (urine or serum hCG) — always first
TSH and prolactin
FSH (high → POI; low/normal → central or PCOS)
If hyperandrogenism: total testosterone, DHEAS, 17-OHP
Estradiol if FSH abnormal
Imaging
Pelvic ultrasound if structural cause suspected
Brain MRI (pituitary protocol) for elevated prolactin or hypogonadotropic hypogonadism
Hysteroscopy or saline sonohysterography if Asherman suspected (history of D&C, endometritis)
Diagnostic algorithm
flowchart TD
A[Secondary amenorrhea] --> B[hCG]
B -->|Positive| C[Pregnancy]
B -->|Negative| D[TSH, prolactin]
D -->|High prolactin| E[Pituitary MRI<br/>Dopamine agonist]
D -->|Abnormal TSH| F[Thyroid treatment]
D -->|Normal| G[FSH, estradiol]
G -->|High FSH| H[Primary ovarian<br/>insufficiency<br/>repeat in 1 month]
G -->|Low/normal FSH| I{Hyperandrogenism?}
I -->|Yes| J[PCOS workup]
I -->|No| K[Progesterone challenge]
K -->|Withdrawal bleed| L[Anovulation:<br/>functional HA, PCOS]
K -->|No bleed| M[E+P challenge:<br/>bleed = outflow OK<br/>no bleed = Asherman]
Algorithm for secondary amenorrhea — pregnancy first, then TSH/prolactin/FSH stratify.
Treatment
First-line
Treat the underlying cause
Pregnancy: prenatal care
PCOS: see PCOS entry — COCP or cyclic progestin
Functional hypothalamic amenorrhea: nutritional restoration, reduce exercise, address stress; CBT for those with eating disorder
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.