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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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. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.