Secondary amenorrhoea

• Secondary amenorrhoea is the absence of a menstrual period in someone who has previously menstruated, lasting more than three months in an adult or more than 90 days in an adolescent.
• It is not a diagnosis: it is a symptom. The commonest causes are pregnancy, hypothalamic suppression (stress, weight loss, exercise), polycystic ovary syndrome (PCOS), hyperprolactinaemia, premature ovarian insufficiency (POI) and intrauterine adhesions (Asherman syndrome).
• The first question is where the lesion sits: outflow tract (uterus), ovary, or hypothalamus/pituitary.
• Pregnancy is ruled out before anything else, then a short core set of tests (FSH, LH, oestradiol, prolactin, TSH, testosterone, pelvic ultrasound) localises the problem.
• Treatment follows the cause: physiological hormone replacement for POI, restoration of energy balance for hypothalamic amenorrhoea, dopamine agonists for prolactinoma, cycle regulation for PCOS, and hysteroscopic repair for Asherman syndrome.

By the end of this page you should be able to:

1. Define secondary amenorrhoea and separate it from primary amenorrhoea and from still-occurring irregular cycles.
2. Classify the causes by anatomical level (hypothalamus, pituitary, ovary, uterus/outflow tract) and by oestrogen status.
3. Plan the investigation in a sensible order, starting with a pregnancy test.
4. Recognise active red flags (pregnancy with pain or bleeding, virilisation, visual field loss, severe eating disorder, possible POI under 40).
5. Explain the management of POI, functional hypothalamic amenorrhoea, PCOS, hyperprolactinaemia and Asherman syndrome, including the specific drug doses.
6. Name the guideline bodies that shape this area (ASRM, RCOG, ACOG, NICE, WHO) and the editions used.

The distinction from primary amenorrhoea (periods never started by age 15, or by 3 years after breast development) matters greatly, because once menarche has occurred congenital absence of the uterus or vagina and complete androgen insensitivity are effectively ruled out, and the list of causes narrows ^[1]. Irregular cycles that are still occurring (oligomenorrhoea, defined as cycles under 21 or over 35 days, or fewer than 8 cycles per year once 3 years past menarche) need a different first question: are these still cycles, or have they stopped altogether ^[3]? The same investigations apply, but stopping is more urgent than irregularity.

Secondary amenorrhoea not due to pregnancy, lactation or natural menopause affects roughly 3 to 4% of women of reproductive age ^[1]. POI, one of the rarer causes, affects up to 4% of women by age 40 and is much rarer before 30 ^[1]. POI is the leading single cause of primary amenorrhoea; secondary amenorrhoea has a shorter list. The incidence of amenorrhoea rises sharply with eating disorders, intensive athletic training and endocrine conditions such as hyperprolactinaemia. Rarer but important, because they are more dangerous, are androgen-secreting tumours and adrenal pathology. ^[2]

The most useful clinical division is by anatomical level (where the lesion sits) and by what happens to oestrogen. A patient with low or normal FSH and low oestrogen has a central problem; high FSH with low oestrogen has an ovarian problem; a mechanical problem spares oestrogen and may give a progestin-withdrawal bleed without true cycling.

† In the source table, chronic anovulation including PCOS is listed under categories rather than as a separate percentage, and is counted within the low/normal FSH group depending on the patient; published series vary widely.

Any missed or late period in a sexually active person is pregnancy until proven otherwise. Significant abdominal pain, shoulder-tip pain, a positive pregnancy test with vaginal bleeding, or haemodynamic instability defines an emergency (ectopic pregnancy or miscarriage). Once pregnancy is excluded, work through the other causes.

POI is ovarian follicle failure before age 40 (two standard deviations below the average age of natural menopause, 51 years). It presents as four or more months of oligo- or amenorrhoea with menopausal-range FSH (over 25 IU/L on two occasions four to six weeks apart) and low oestradiol ^[1][2]. Most cases remain idiopathic; recent reviews place idiopathic POI at roughly 39 to 67% of cases, although older literature often quoted 70 to 90% ^[2]. Genetic, autoimmune, iatrogenic (chemotherapy, radiotherapy, pelvic surgery) and X-chromosome causes are recognised among the remainder ^[2]. It may be intermittent: over a quarter of women with POI have intermittent resumption of ovarian activity, and 5 to 10% conceive spontaneously ^[1]. The practical priorities are karyotype, FMR1 premutation testing, 21-hydroxylase antibody testing, DEXA and long-term hormone replacement ^[1] (see below).

This is central suppression of GnRH pulsatility by low energy availability, weight loss, excessive exercise or severe stress. It is a diagnosis of exclusion: low or low-normal LH and FSH, low oestradiol, and no anatomical or hormonal cause found ^[1]. It overlaps with the female athlete triad (oligo-amenorrhoea, low energy availability and low bone mineral density). Treatment targets restoration of ovulation: weight recovery and increased energy intake, reduced exercise intensity, stress reduction, psychological support and specialist dietetic input; severe cases (bradycardia, hypotension, electrolyte disturbance) need inpatient care ^[1]. Avoid bisphosphonates in this group (the Endocrine Society 2017 FHA guideline, as cited in Ref 1). Physiological HRT as used for POI may support oestrogen status while the underlying cause is reversed, but it is not a substitute for behavioural recovery ^[1]. ^[2]

PCOS accounts for a large share of normogonadotrophic chronic anovulatory cases and is the commonest endocrinopathy in reproductive-aged women (prevalence 10 to 13% by the Rotterdam criteria). Diagnosis in adults requires two of three: oligo- or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology. The 2023 International Evidence-based Guideline (supported by ASRM, Endocrine Society, ESHRE and European Society of Endocrinology; Ref 3) adds serum AMH as an alternative to ultrasound for defining polycystic morphology in adults, and defines irregular cycles (under 21 or over 35 days, or under 8 cycles a year, more than 3 years after menarche; any cycle over 90 days, 1 year after menarche). Adolescents need hyperandrogenism and persisting oligomenorrhoea for a provisional label, because anovulation can be physiological at that age. Avoid diagnosing PCOS prematurely. Management: healthy eating and regular exercise for everyone, weight reduction where body mass index is raised (which can restart cycles), combined oral contraceptives first-line for menstrual irregularity, hirsutism, acne and endometrial protection (note the guideline suggests ethinylestradiol under 30 micrograms where possible, and flags the 35 microgram ethinylestradiol plus cyproterone acetate as second-line because of venous thromboembolic risk), metformin (suggested maximum 2.5 g daily in adults, start with 500 mg increments every 1 to 2 weeks) for metabolic risk and where the pill is contraindicated, and letrozole (first-line for ovulation induction when fertility is wanted). Screen for glucose tolerance, lipids and blood pressure because of the metabolic consequences ^[3][1].

Prolactin suppresses GnRH. Causes are pregnancy, a pituitary adenoma (micro- or macroprolactinoma), dopamine-blocking medications (antipsychotics, metoclopramide, some antihypertensives), hypothyroidism and renal disease. Dopamine agonists are the first-line treatment for a prolactin-secreting tumour: cabergoline, starting at 0.25 mg by mouth twice weekly, titrating by 0.25 mg twice weekly at intervals of at least 4 weeks to a maximum of 1 mg twice weekly, with echocardiographic surveillance every 6 to 12 months because of valvulopathy risk ^[6]. If prolactin normalises after stopping an offending drug, no tumour imaging is needed; otherwise MRI of the pituitary is required. Large tumours with pressure effects may need surgical resection ^[1].

Amenorrhoea with a normal hypothalamopituitary-ovarian axis (normal FSH, LH, oestradiol) after curettage of a recently pregnant uterus, or after hysteroscopic surgery, uterine artery embolisation or infection (including tuberculosis), points to a scarred endometrium. Patients may have a false progestin-withdrawal bleed from residual islands of endometrium, or none. Contrast sonohysterography or hysterosalpingography is helpful; hysteroscopy confirms the diagnosis ^[1]. NICE NG257 recommends offering hysteroscopic adhesiolysis for women with amenorrhoea caused by intrauterine adhesions, because it is likely to restore periods and improve the chance of pregnancy, followed by postoperative oestrogen to grow the endometrium and (optionally) a balloon or stent to prevent re-adhesion, with a second-look hysteroscopy ^[4][1].

Both hypothyroidism and hyperthyroidism disrupt cycling. Late-onset 21-hydroxylase deficiency presents as hyperandrogenic amenorrhoea and should be excluded before labelling PCOS; a serum 17-hydroxyprogesterone, and where high an ACTH stimulation test, confirms it. An adrenal or ovarian androgen-secreting tumour is suspected when virilisation is rapid or androgens are markedly raised. Cushing syndrome is screened for with a 24-hour urine free cortisol, late-night salivary cortisol or dexamethasone suppression test when the clinical picture fits ^[1].

Record body mass index and waist circumference, signs of oestrogen deficiency (atrophic vulvovaginal mucosa, reduced bone mineral density), galactorrhoea on breast expression, and androgen excess (hirsutism scored with a modified Ferriman-Gallwey score, acne, female-pattern hair loss; a score of 4 to 6 detects hirsutism depending on ethnicity) ^[3]. Take blood pressure. Perform a pelvic examination looking for uterine size and cervical patency, and note signs of cortisol excess (moon face, central obesity, striae). A pelvic ultrasound completes the bedside assessment.

1. Pregnancy test first (urine hCG; if negative but strongly suspected, use serum).
2. Core hormone panel in the morning, in the early follicular phase if periods have resumed briefly: FSH, LH, oestradiol, prolactin (drawn without nipple stimulation, sample taken after 15 to 30 minutes' rest), TSH (with free T4 if TSH abnormal), testosterone (free or total, with sex-hormone-binding globulin). Add 17-hydroxyprogesterone and DHEAS when there is hyperandrogenism, and screening for Cushing syndrome (24-hour urine free cortisol, late-night salivary cortisol, or dexamethasone suppression) when it fits.
3. Pelvic (ideally transvaginal) ultrasound: uterus present or absent, endometrial thickness and pattern, ovarian morphology, and a mechanical cause such as adhesions or a mass.
4. If POI is suspected (high FSH, low oestradiol, under 40): repeat FSH on two occasions at least one month apart if the first result is equivocal; then karyotype (to detect Turner syndrome and variants), FMR1 premutation testing, 21-hydroxylase antibodies, and DEXA for baseline bone mineral density. Repeat DEXA in two to five years where response is being monitored ^[1][2].
5. If prolactin is high and persists after removing the offending drug: MRI of the pituitary.
6. If the uterus or cavity is suspect: contrast sonohysterography or hysterosalpingography, then confirmatory hysteroscopy ^[1].
7. Metabolic screen in PCOS: lipid profile, oral glucose tolerance test where available, and blood pressure each visit ^[3].

• Pregnancy pathway: manage according to standard emergency care; see the ectopic pregnancy topic.
• Red-flag causes (suspected tumour, severe eating disorder, visual loss, virilisation) are referred urgently.
• If POI or hypothalamic amenorrhoea is confirmed: avoid leaving the patient oestrogen-deficient; start a plan at the first visit (replacement or recovery).
• If Asherman or outflow obstruction is possible: do not simply prescribe hormones for months; image the cavity.

Premature ovarian insufficiency. Treat as an oestrogen-deficiency state with young patients' doses, not menopausal dosing. The best-evidence regimen, cited in the secondary-amenorrhoea literature as "physiologic" HRT, is 100 micrograms transdermal 17-beta-oestradiol daily plus medroxyprogesterone acetate 10 mg by mouth daily for the first 12 days of each calendar month ^[1][6]. Alternatives include transdermal 100 to 150 micrograms 17-beta-oestradiol with cyclic progestogen 10 to 200 mg daily for 12 to 14 days monthly, oral oestradiol at least 2 mg daily, or, if contraception is wanted, the combined ethinylestradiol pill (which maintains bone density but is less physiological, carries thrombotic risk and is not the best-evidence regimen) ^[1][2]. Replace oestrogen until the average age of natural menopause (50 to 51 years), when the risk-benefit ratio is reviewed ^[1][2]. Counselling: 5 to 10% conceive spontaneously, and HRT does not suppress ovulation, so offer contraception (including the levonorgestrel intrauterine system combined with oestradiol) unless pregnancy is wanted ^[1]. Screen for karyotype (Turner syndrome), FMR1 premutation and 21-hydroxylase antibodies; ensure adequate calcium (1200 mg elemental) and vitamin D (800 IU) daily with weight-bearing exercise ^[1]. Add DEXA at baseline and in 2 to 5 years if response is monitored ^[2]. Absolute contraindication to HRT is survival of an oestrogen-dependent cancer; take individualised advice for other hormone-sensitive tumours and for raised thrombotic risk, for whom transdermal 17-beta-oestradiol is the preferred route ^[2]. ^[3]

Functional hypothalamic amenorrhoea. Recover energy balance: increase caloric intake, reduce training, address stress and eating behaviour, with dietetic and psychological support and multidisciplinary care. This is the only treatment that restores ovulation. Severe cases (bradycardia, hypotension, postural instability, electrolyte disturbance) require inpatient care. Bisphosphonates are not recommended. HRT may bridge oestrogen status, and once remission begins ovulation may return before menses do, so advise on pregnancy risk ^[1].

PCOS. Start with explanation, support and lifestyle changes (weight reduction in those with raised body mass index can restart cycles). Offer combined oral contraceptives for cycle control, hirsutism, acne and endometrial protection ^[3]. Add metformin when glucose tolerance is impaired, where the pill is contraindicated and for metabolic risk, up to 2.5 g daily in adults (2 g in adolescents) ^[3]. Treat late-onset congenital adrenal hyperplasia and exclude an androgen-secreting tumour before attributing amenorrhoea to PCOS. For fertility, letrozole is first-line for ovulation induction ^[3].

Hyperprolactinaemia. Stop or change an offending drug if it is safe to do so; otherwise arrange MRI of the pituitary, and a dopamine agonist (cabergoline as above, starting 0.25 mg twice weekly, titrating by 0.25 mg twice weekly at intervals of at least 4 weeks to a maximum of 1 mg twice weekly, with echocardiography every 6 to 12 months). Surgery is reserved for tumours that do not respond to medication or have clear pressure effects ^[1][6].

Asherman syndrome. Hysteroscopic adhesiolysis (NICE NG257 recommends it) followed by oestrogen to regenerate endometrium and prevention of re-adhesion; confirm patency and cavity shape before each further cycle ^[4][1].

• Any red-flag cause, pregnancy complication, or severe eating disorder: emergency or urgent referral.
• POI: refer to reproductive endocrinology or a specialist clinic for long-term care, and to genetics for FMR1 and karyotype. Refer for fertility options (oocyte donation).
• Complex PCOS (fertility, refractory hirsutism, suspected tumour) and all hyperprolactinaemia requiring MRI or surgery: specialist referral.
• Asherman syndrome: refer to an experienced hysteroscopic surgeon.

• Adolescents (ACOG Committee Opinion 651, 2015, as cited within Ref 1): an interval longer than 90 days is abnormal even early after menarche. PCOS is frequently over-diagnosed in this age group; diagnosis rests on persisting oligomenorrhoea plus hyperandrogenism, with ultrasound unreliable.
• Athletes and women with low body mass index: relative energy deficiency in sport (RED-S) suppresses the axis. Treat by restoring energy availability, not by the pill, which masks the problem; add HRT if premature loss of bone is suspected.
• Women wanting pregnancy: change the plan to ovulation-inducing treatment (clinical hypogonadotropic hypogonadism: weight restoration plus gonadotrophins; PCOS: letrozole; POI: oocyte donation or, for early cases, fertility preservation). NICE NG257 supports gonadotrophins with LH activity for hypogonadotropic hypogonadism, and weight recovery when BMI is under 18.5 kg per square metre ^[4].
• After pregnancy loss or curettage: always consider Asherman syndrome and cervical stenosis before reassuring.
• Menopausal-age patients (over 45) being assessed for secondary amenorrhoea: do not over-investigate once age and clinical picture fit physiologic transition.

The core work-up (pregnancy test, FSH, prolactin, TSH, testosterone, basic pelvic ultrasound) is cheap and widely available, and combined with a careful history it reaches a diagnosis in most patients. Serum FSH above 25 IU/L taken twice, four weeks apart, with a low oestradiol, is enough to diagnose POI even where karyotyping is unavailable; genetic testing can wait. Where hysteroscopy is unavailable, a trial of combined oestrogen and progestin followed by a paediatric speculum examination and imaging may help, but referral should be arranged for suspected Asherman. Oral progestin supplies and basic HRT formulations cover most needs where transdermal 17-beta-oestradiol is not available. The WHO Medical Eligibility Criteria for Contraceptive Use (fifth edition, 2015; Ref 5) is the standard reference for choosing hormonal contraception in women with medical conditions.

• Doing a progestin challenge to "restart" periods and then reassuring the patient when she bleeds: bleeding after progestin only shows there is some endometrium and oestrogen; it says nothing about which cause is present, and it delays diagnosis ^[1].
• Accepting the combined oral contraceptive as "hormone replacement therapy" for POI: it is not physiological, it has thrombotic risk and it is not the best-evidence regimen ^[1].
• Diagnosing PCOS after only one missed period in a teenager, or investigating with a pelvic ultrasound because the patient wants one: unnecessary investigations are as bad as missed ones ^[3].
• Withdrawing the combined pill and forgetting to manage contraception for three months while androgens are rechecked ^[3].
• Starting high-dose oestrogen in POI without progestin protection in a woman with a uterus: risk of endometrial hyperplasia ^[2].
• Forgetting autoimmune adrenal failure in a woman with POI and positive autoantibodies, which can be life threatening if missed.

Uterine inversion, rupture and Sheehan syndrome; hyperprolactinaemia and prolactinoma; hypothyroidism and hyperthyroidism; hypopituitarism; polycystic ovary syndrome; disorders of sex development; ectopic pregnancy.

See the front matter for the numbered reference list (^[1] Nelson 2023 secondary-amenorrhoea review; ^[2] Federici 2024 POI update; ^[3] Teede 2023 International PCOS Guideline; ^[4] NICE NG257 2026; ^[5] WHO MEC 5th edition 2015; ^[6] DailyMed cabergoline label 2025). These six sources were opened for every dose, threshold and statement above. The named guideline bodies used are the ASRM-supported 2023 International PCOS Guideline; NICE NG257 2026; ACOG Committee Opinion 651 2015 (cited within Ref 1); Endocrine Society functional hypothalamic amenorrhoea guideline 2017 (cited within Ref 1); WHO MEC 5th edition 2015; RCOG and British Menopause Society frameworks for POI care; and the ESHRE criterion for POI (FSH over 25 IU/L twice, 4 weeks apart) as restated in Ref 2.