Primary amenorrhoea

• Primary amenorrhoea is the lifelong absence of menstruation. It deserves investigation when a girl has not had a period by 15 years with normal puberty, by 13 years without any puberty, or more than 3 years after breast budding.
• The causes split into four groups decided by two questions: is a uterus present, and has oestrogen-driven breast development occurred? Those two answers point to an outflow obstruction, absent Müllerian structures or androgen insensitivity, ovarian failure with high FSH, or a central (hypogonadotropic) problem.
• The first-line tests for almost everyone are a pregnancy test, pelvic ultrasound, FSH, LH, oestradiol, prolactin and thyroid-stimulating hormone.
• A few findings are urgent red flags: cyclical monthly pain with no bleeding, headache or visual disturbance, severe underweight, short stature with a webbed neck, or any sign of virilisation.
• Treatment follows the cause: surgically relieve an obstruction, give oestrogen (with later progestin) where the ovaries have failed, "jump-start" delayed puberty when appropriate, and restore energy balance in functional hypothalamic amenorrhoea.

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

1. Define primary amenorrhoea using the thresholds in current guidelines and explain why they differ slightly between sources.
2. Classify the common causes by uterus, breast development and FSH, and name the typical example in each group.
3. Take a focused history and perform the key examinations that split these groups apart.
4. Order investigations rationally and interpret FSH and testosterone results in context.
5. Outline immediate and definitive management, including bone protection and fertility counselling.
6. Recognise the common traps that delay diagnosis.

The normal anchor points are these: median menarche is about 12 to 13 years (about 12.4 years in many series), breast budding (thelarche) appears between about 8 and 10 years, and menarche follows thelarche by about 2 to 3 years. Menstrual cycles in adolescents are usually 20 to 45 days apart, with a mean of 32 days in the first gynecologic year, and bleeding lasts up to 7 days. ^[4]

Guidelines differ slightly in the age at which absence of periods becomes "primary amenorrhoea", because they are quoting different percentiles and populations.

• ASRM (2024): investigate failure to menstruate by 15 years with normal secondary sexual development; within 5 years after breast development if that began before 10 years; and failure to initiate breast development by 13 years. ^[3]
• ACOG Committee Opinion No. 651 (2015, reaffirmed 2025): investigate no menarche by 15 years, or not within 3 years of thelarche; no breast development by 13 years. ^[4]
• NICE CKS (2024): variably defined as 15 or 16 years with normal secondary sexual characteristics, or 13 or 14 years without them. ^[5]
• RCOG Core Knowledge course: failure to menstruate by 15 years with normal secondary sexual characteristics, or by 13 years without other evidence of puberty. ^[6]
• StatPearls: no history of menstruation by 15 years or 3 years after thelarche; evaluate delayed puberty at 13 years or younger without breast development. ^[1]

Because the ASRM and ACOG definitions (15 years, or 13 years without puberty) are the most widely used in practice, and because earlier referral is safe, this page uses them as the working rule: refer by 13 years if there is no puberty, or by 15 years if puberty is normal but no period has started. Where local pathways quote 16 or 14, follow them, and always investigate earlier if any red flag is present. ^[5]

Amenorrhoea not due to pregnancy, lactation or menopause affects roughly 3 to 4% of women; primary amenorrhoea itself is much less common. ^[7]

The World Health Organization groups amenorrhoea by gonadotrophin and oestrogen status (WHO groups I to III), a scheme summarised by ASRM (2008). ^[7] In group I there is low oestrogen and low or normal FSH (a hypothalamic or pituitary problem); in group II there is normal oestrogen and FSH (often PCOS or anatomic); in group III there is low oestrogen and a high FSH (ovarian failure). The table below uses the more bedside-friendly split by uterus and breast development, which is what a student needs in a clinic.

Müllerian agenesis accounts for roughly 10 to 15% of primary amenorrhoea and complete androgen insensitivity for about 5%. ^[1][3] Gonadal dysfunction is the single largest group, at about 43%, followed by constitutional delay at about 14%. ^[1]

• Turner syndrome (45,X or mosaic) is the commonest chromosomal cause. It presents with hypergonadotropic hypogonadism and absent puberty in many, although about 10% retain Y chromosomal material and carry a germ-cell tumour risk. ^[2]
• Müllerian agenesis (MRKH) is multifactorial agenesis of the uterus, tubes, cervix and upper vagina. Ovaries are normal, so oestrogen is normal, puberty is normal, and there is no need for hormone replacement. ^[2]
• Complete androgen insensitivity (46,XY, with testes) gives normal breast development through aromatised testosterone, but sparse or absent pubic and axillary hair and no uterus. Testosterone is in the normal male range or higher. ^[3]
• Imperforate hymen and transverse vaginal septum are outflow obstructions with a present uterus and normal hormones. They classically present with cyclical abdominal pain and a bulging bluish membrane at the introitus. ^[1]
• Hypogonadotropic causes include constitutional delay (a diagnosis of exclusion), functional hypothalamic amenorrhoea, Kallmann syndrome (often with anosmia), and intracranial lesions. ^[1][3]

Red flags are findings that either are themselves urgent or point to a serious underlying cause. Each should prompt referral rather than watchful waiting.

• Cyclical monthly lower abdominal pain with no bleeding. This suggests haematocolpos from an outflow obstruction. Relieve it promptly: retained blood can distend the uterus, damage tubes and risk infection. ^[5]
• Headache, visual disturbance, papilloedema, or vomiting. Think pituitary adenoma, craniopharyngioma or other intracranial mass. ^[5]
• Galactorrhoea, especially with a prolactin above 1000 mIU/L, which usually warrants pituitary imaging. ^[5][7]
• Short stature, webbed neck, wide carrying angle, or scoliosis. Turner syndrome. ^[5]
• Anosmia. Kallmann syndrome. ^[5]
• Hirsutism, acne, clitoromegaly or deepening voice. Androgen excess: PCOS, non-classic congenital adrenal hyperplasia, or an androgen-secreting tumour. ^[5][1]
• Very low body mass index, weight loss, restrictive eating, or excessive exercise. Functional hypothalamic amenorrhoea and impaired bone health. ^[5][1]
• Primary amenorrhoea at any age with a known DSD, atypical genitalia, or a palpable inguinal mass (possible testis). ^[2]

Every question below comes from a guideline and has a reason attached.

Pubertal milestones and growth. When did breast budding and pubic hair start? When did growth accelerate? A clear timeline separates an isolated outflow problem (normal puberty) from delayed puberty (a hypothalamic or gonadal problem). Note the age at menarche of mother and sisters, since late menarche runs in families. ^[5][1]

Pain. Is there cyclical lower abdominal pain? That is the hallmark of haematocolpos and distinguishes an obstruction from an absence of menstruation. ^[5]

Bleeding pattern. Has there ever been any bleeding at all, even spotting? An episode of bleeding reclassifies the problem as secondary amenorrhoea. ^[3]

Weight, exercise, stress, and chronic illness. Disordered eating, rapid weight loss, intensive training, and perceived stress suppress GnRH and cause functional hypothalamic amenorrhoea. Ask about chronic systemic disease too. ^[5][1]

Headache, visual change, galactorrhoea. Suggest a prolactinoma or other pituitary lesion. ^[5]

Anosmia. Suggests Kallmann syndrome. ^[5]

Androgen excess. Acne and hirsutism point to PCOS or non-classic congenital adrenal hyperplasia; virilisation raises concern for an androgen-secreting tumour. ^[5]

Sexual history and contraception. Exclude pregnancy and a contraceptive cause; ask sensitively, and consider the possibility of sexual abuse. ^[5]

Medication and treatment history. Antipsychotics and some antidepressants raise prolactin; prior chemotherapy or radiotherapy can cause ovarian failure. ^[5][1]

Family history. Genetic anomalies such as androgen insensitivity or DSD, and a family history of infertility. ^[5]

Anthropometry. Height and weight (BMI). Short stature strongly suggests Turner syndrome; a low BMI suggests FHA; a high BMI suggests PCOS. ^[5][1]

Pubertal staging and oestrogen status. Tanner breast stage is the practical marker of oestrogen exposure. Presence of breast buds means the ovaries have produced oestrogen; absent breast development at 13 years needs its own evaluation. ^[4][1]

Turner stigmata. Short stature, webbed neck, low posterior hairline, shield chest with widely spaced nipples, wide carrying angle, scoliosis. ^[5]

Cushing and thyroid. Striae, buffalo hump, central obesity, easy bruising, hypertension, proximal weakness for Cushing; goitre or tremor for thyroid disease. ^[5]

Breast examination for galactorrhoea. ^[5]

Hirsutism, acne, virilisation. Inspect for clitoromegaly and measure blood pressure (hypertension suggests 17alpha-hydroxylase deficiency or Cushing). ^[5][1]

Genital examination where appropriate. In a sexually active girl or older woman a pelvic examination is appropriate; in young girls who are not sexually active it is not, and ultrasound takes its place. ^[5] On examination, a blind or absent vagina with normal breast development points to Müllerian agenesis, transverse vaginal septum, or androgen insensitivity. Visualising the cervix tells you a uterus is present. Pelvic examination is abnormal in roughly 15% of primary amenorrhoea. ^[3]

Imperforate hymen. Separating the labia may show a bulging, blue-coloured membrane; a pelvic mass may be palpable. ^[5]

Features of androgen insensitivity. Normal breast development with absent axillary and pubic hair, sometimes with testes palpable in the inguinal canal or labia. ^[5][3]

Neurological examination. Peripheral vision and papilloedema if a pituitary lesion is suspected. ^[5]

If a pelvic examination is not feasible, an abdominal or transabdominal ultrasound can confirm the presence or absence of the uterus, although it can miss a rudimentary or prepubertal uterus. ^[3]

The investigations change with the findings, but the starting set is the same for almost everyone.

1. Pregnancy test (urine or serum) -- always first. Ovulation precedes the first period, so a girl who has never menstruated can still be pregnant. ^[1][3]

2. Pelvic ultrasound (transabdominal) to answer one question: is a uterus (and vagina) present? ^[1][5]

3. Serum FSH, LH and oestradiol to separate ovarian from central causes. ^[1][3] A low or inappropriately normal FSH means hypogonadotropic hypogonadism (hypothalamus or pituitary); a high FSH means hypergonadotropic hypogonadism (ovarian failure). Oestradiol is needed to interpret the FSH. With normal FSH and oestradiol alongside a present uterus, the problem is usually anatomic or anovulatory. ^[1][3][7]

4. Serum prolactin and TSH to exclude hyperprolactinaemia and thyroid disease. ^[1][3][5]

5. Karyotype if FSH is high (gonadal dysgenesis or POI), if the uterus is absent, or if the girl is under 30 years with gonadal failure, to look for a Y chromosome (as in mosaic Turner or Swyer syndrome). ^[3][2][7]

6. Serum testosterone once uterovaginal agenesis is confirmed, or if there are signs of androgen excess. Testosterone in the normal male range or higher points to complete androgen insensitivity; low or normal testosterone points to Müllerian agenesis. ^[3] In anovulatory presentations with androgen excess, add 17-hydroxyprogesterone, DHEAS, androstenedione and (if needed) a synacthen test. ^[1][2]

7. Pituitary imaging (MRI) if prolactin is persistently raised above 1000 mIU/L, or if there are headache or visual symptoms. ^[5][7]

8. Additional, context-specific tests as suggested by the clinical picture: bone age X-ray and IGF-1 if growth is slow; celiac screen (tissue transglutaminase IgA) if BMI is low; MRI of the pelvis for complex anatomy; head imaging for central red flags. ^[1]

Immediate management is only needed for the urgent situations:

• Haematocolpos/haematometra from an outflow obstruction. Relieve it surgically (hymenotomy or septum resection) rather than waiting; delay risks infection, tubal damage and fertility. ^[5]
• Suspected intracranial lesion. Urgent neuroimaging and endocrine referral for headache, visual disturbance or markedly elevated prolactin. ^[5]
• Severe FHA/eating disorder. Immediate referral to an age-appropriate eating-disorder service when an eating disorder is suspected; restore nutrition. ^[5]
• Virilisation or a palpable gonad. Urgent gynaecology/endocrinology review to exclude an androgen-secreting tumour. ^[5][1]

Definitive treatment is always of the underlying cause, plus what the patient needs for health and future fertility.

Outflow obstruction. Surgical correction (hymenotomy, resection of a transverse vaginal septum, cervical reconstruction where appropriate) is the definitive treatment and usually restores normal menstruation. ^[1]

Müllerian agenesis. No hormone replacement is needed, because ovarian function is normal. Offer renal and spinal imaging, counselling about fertility (egg freezing and surrogacy where legal, or adoption), and creation of a functional vagina only when the patient wants it and can take part in the decision: self-dilation achieves success in 90 to 96% of cases and is first line. ^[2]

Complete androgen insensitivity. Delay gonadectomy until breast development and adult height are complete, because the risk of malignancy is relatively low (about 2%) before 20 years, and the testes provide the oestrogen that drives puberty. If gonadectomy is done, start hormone replacement. Vaginal creation is offered on the same principles as for Müllerian agenesis. ^[2][3]

Ovarian failure / hypergonadotropic hypogonadism (including Turner syndrome). Induce puberty with low-dose oestrogen from around 11 to 12 years (after reasonable growth potential is achieved) and titrate over 2 to 3 years, then add cyclic progestin for endometrial protection from the first bleed or about 2 years after starting oestrogen. Continue hormone therapy until at least the natural age of menopause (about 50). ^[2][1]

Bone protection matters whenever oestrogen is absent: calcium 1200 mg orally daily, vitamin D 1000 IU daily, routine weight-bearing exercise, and avoidance of smoking and excess alcohol. Screen for comorbid conditions (such as hypothyroidism), which are more common in this group. ^[1][5]

Fertility counselling is essential: a small proportion of patients with POI have remaining reproductive capacity; Turner patients with spontaneous menarche may be offered fertility preservation; DSD patients require individualised counselling. ^[2][1]

Hypogonadotropic hypogonadism. Treat the cause. For functional hypothalamic amenorrhoea the management is weight restoration, stress reduction, lifestyle change and dietary modification, with cognitive behavioural therapy where severe stress is involved. Combined oral contraceptives alone are not recommended therapy for amenorrhoea here, and do not protect bone density on their own. ^[1][5]

For constitutional delay of growth and puberty, reasonable options are observation for 6 months, or "jump-start" low-dose oestrogen for 3 to 6 months followed by 4 to 6 months of observation. Persistent cases need endocrinology. ^[1]

Hypothalamic/pituitary tumours need targeted medical or surgical management and referral to endocrinology and neurosurgery. ^[1]

PCOS or other androgen-excess causes are managed through the usual PCOS pathway (weight loss and exercise, metabolic screening, and cycle protection), discussed in the PCOS topic. ^[5]

Bone protection in FHA specifically. If amenorrhoea persists for more than 6 months, consider a DXA scan and, if low bone density is confirmed or amenorrhoea persists beyond 12 months, specialist-supervised hormone replacement therapy with transdermal oestrogen and cyclic progesterone. The oral contraceptive pill is not evidenced for protecting bone density. ^[5]

All patients with primary amenorrhoea need specialist assessment, but the routing differs. ^[5]

• Refer by 13 years if no secondary sexual characteristics have started, and by 15 years if they are normal but no period has occurred (or 3 years after thelarche). Refer earlier for pain, growth retardation, androgen excess, galactorrhoea, suspected malformation, chromosomal anomaly or eating disorder. ^[5][4]
• Refer to gynaecology (preferably with adolescent interest) for most patients, especially outflow tract problems. ^[5]
• Refer to endocrinology for absent puberty by 13, hyperprolactinaemia, thyroid disease, or features of androgen excess. ^[5]
• Suspected eating disorder: immediate referral to an age-appropriate eating-disorder service. ^[5]

Adolescents. Puberty is psychologically charged. A multidisciplinary approach (gynaecology, endocrinology, psychology, when needed) is recommended, with careful counselling at each step. ^[2][5]

Turner syndrome. Diagnose early where possible, but remember phenotype varies widely, so diagnosis can be delayed. Plan pubertal induction, cardiovascular and renal screening, and fertility counselling. ^[2]

Differences of sex development. Patients with 46,XY gonadal dysgenesis (Swyer syndrome) need gonadectomy for malignancy risk and oestrogen replacement; those with mixed gonadal dysgenesis or ovotesticular DSD need shared decision-making about gonadal management and fertility potential. ^[2]

Athletes and low-energy states. Relative energy deficiency in sport (RED-S) can produce primary amenorrhoea before menarche never happens. Management is energy repletion and weight restoration, not hormones alone. ^[5][1]

Low-resource settings. A transabdominal ultrasound and basic hormone panel usually make the diagnosis; MRI of the pelvis and brain, karyotype, and gonadectomy require referral. Self-dilation is a low-cost, effective first-line method for vaginal creation. Hormone replacement with affordable preparations and calcium/vitamin D remain the standard for ovarian failure. ^[2][1]

• "No period" is not "no puberty". Congenital absence of the uterus (MRKH) and androgen insensitivity both occur in girls with completely normal breast development. ^[3]
• Do not label constitutional delay early. It is a diagnosis of exclusion after central and gonadal causes have been considered. ^[3]
• A pregnant teenager who has never menstruated is possible. Always do the pregnancy test. ^[1]
• Do not use the combined pill to "treat" FHA. It does not protect bone density and masks the underlying problem. ^[1][5]
• Do not mix up MRKH and CAIS. Testosterone level (and karyotype) separates them: male-range testosterone means CAIS. ^[3]
• Interpret FSH with oestradiol, and remember normal FSH/oestradiol means look for an anatomic or anovulatory cause. ^[1]
• Missing Y chromosomal material. Always karyotype gonadal failure and uterovaginal agenesis, and counsel on germ-cell tumour risk. ^[2][7]
• Imperforate hymen can be missed. Inspect the introitus in any girl with cyclic pain and no bleeding. ^[5]

• Primary amenorrhoea is the lifelong absence of menstruation, worked up by 13 years if there is no puberty or by 15 years (or 3 years after thelarche) if puberty is normal. ^[3][4]
• Normal milestones: thelarche 8 to 10 years, menarche 12 to 13 years (within 2 to 3 years of thelarche). ^[1][4]
• The largest cause groups are gonadal dysfunction (~43%) and constitutional delay (~14%); Müllerian agenesis is ~10 to 15% and CAIS ~5%. ^[1][3]
• Two questions guide the whole assessment: is a uterus present, and is there oestrogen-driven breast development? ^[1][3]
• First-line tests: pregnancy test, pelvic ultrasound, FSH, LH, oestradiol, prolactin, TSH; add karyotype and testosterone as the examination dictates. ^[1][3][5]
• High FSH means ovarian failure; low or normal FSH means a hypothalamic or pituitary problem. ^[1][7]
• A uterus with cyclic pain and no bleeding is an outflow obstruction until proven otherwise, and needs prompt surgical relief. ^[5]
• Testosterone in the male range distinguishes CAIS from Müllerian agenesis. ^[3]
• Functional hypothalamic amenorrhoea is treated by restoring energy balance; combined oral contraceptives are not a substitute and do not protect bone. ^[1][5]
• Hypogonadal patients need oestrogen replacement with progestin protection, continued to about age 50, plus calcium, vitamin D and weight-bearing exercise. ^[1][2]
• Fertility potential must be discussed individually (POI, Turner, DSD, MRKH). ^[2]
• Bone protection: DXA if amenorrhoea persists 6 months or more in FHA, and hormone replacement if low bone density or persistent amenorrhoea beyond 12 months. ^[5]