Previous changes

February 2022 — minor update. A recommendation that the combined oral contraceptive (COC) pill is an option if amenorrhoea persists for more than 12 months to help manage the risk of osteoporosis has been removed from this topic in line with the Endocrine Society guideline Functional hypothalamic amenorrhea: an Endocrine Society clinical practice guideline.

August 2020 — minor update. Broken URL links updated.

November 2019 — minor update. Causes section updated for clarity.

November 2018 — reviewed. A literature search was conducted in October 2018 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. No major changes to recommendations have been made; however, the definitions of primary and secondary amenorrhoea have been amended to include expert opinion in recent review articles.

July 2014 — reviewed. A literature search was conducted in June 2014 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials (RCTs) published since the last revision of this topic. No major changes to recommendations have been made. The management section has been restructured to simplify use.

July to October 2009 — converted from CKS guidance to CKS topic structure. The evidence base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence. There are no major changes to the recommendations.

April 2009 — minor update to include hypopituitarism following traumatic brain injury as a cause of amenorrhoea. 

July to September 2006 — reviewed. Validated in December 2006 and issued in January 2007.

November 2005 — minor technical update. 

February 2005 — updated to include prescribing advice from the Committee on Safety of Medicines (CSM) on the effect of depot medroxyprogesterone acetate contraception on bones. 

July 2003 — reviewed. Validated in September 2003 and issued in October 2003.

January 2000 — written. Validated in March 2000 and issued in May 2000.

New evidence

Evidence-based guidelines

No new evidence-based guidelines since 1 January 2024.

HTAs (Health Technology Assessments)

No new HTAs since 1 January 2024.

Economic appraisals

No new economic appraisals relevant to England since 1 January 2024.

Systematic reviews and meta-analyses

No new systematic review or meta-analysis since 1 January 2024.

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 January 2024.

New policies

No new national policies or guidelines since 1 January 2024.

New safety alerts

No new safety alerts since 1 January 2024.

Changes in product availability

No changes in product availability since 1 January 2024.

What are the causes of primary amenorrhoea?

• Physiological causes:
• • Constitutional delay — no anatomical abnormality, and maturation usually occurs spontaneously by 18 years of age. Secondary sexual characteristics are also likely to be delayed. The condition is frequently familial.
  • Pregnancy.
• Outflow tract abnormalities:
  • Imperforate hymen.
  • Transverse vaginal septum.
  • Müllerian agenesis (congenital condition where the Müllerian ducts do not develop, leading to agenesis or atresia of the vagina and uterus, also known as the Mayer-Rokitansky-Küster-Hauser syndrome).
  • Causes of ambiguous genitalia, such as:
    • 5-alpha-reductase deficiency.
    • Congenital adrenal hyperplasia.
    • Androgen insensitivity syndrome.
• Premature ovarian insufficiency (POI) due to:
  • Chromosomal irregularities (for example Turner's syndrome [46XO] and gonadal agenesis [46XX or 46XY]).
  • Other causes, such as chemotherapy, pelvic radiation, and autoimmune disease.
• Hypothalamic or pituitary dysfunction due to:
  • Stress, excessive exercise, and/or weight loss (functional hypothalamic amenorrhoea).
    • Eating disorders.
    • The term 'female athlete triad' was previously used to describe a medical condition observed in very physically active women (such as distance runners, gymnasts, and dancers) involving low energy availability (with or without eating disorders), menstrual dysfunction, and low bone density. The definition has been broadened to include all active people and is now more commonly called 'relative energy deficiency in sport' (RED-S).
  • Hyperprolactinaemia (for example, caused by prolactinoma or medication).
  • Chronic systemic illness (such as uncontrolled diabetes, severe renal and cardiac disorders, coeliac disease, cancer, and infections [for example tuberculosis]).
  • Other causes of dysfunction of the hypothalamic-pituitary axis, including hypothalamic or pituitary tumours; cranial irradiation; infection or head injury; Kallman's syndrome (congenital gonadotrophin deficiency characterized by anosmia and other cranial anomalies); empty sella syndrome; Laurence–Moon–Biedl syndrome; and Präder–Willi syndrome.
• Endocrine disorders, such as:
  • Hypothyroidism.
  • Hyperthyroidism.
  • Cushing's syndrome.
  • Androgen-secreting tumours.
  • Polycystic ovary syndrome (a rare cause of primary amenorrhoea).

[Practice Committee of the American Society for Reproductive Medicine, 2008; Gordon, 2017; ACOG, 2018b; Klein, 2019; Seppä, 2021; BMJ Best Practice, 2022a; Todd, 2022]

What are the causes of secondary amenorrhoea?

• Physiological causes:
  • Pregnancy.
  • Lactation.
  • Menopause.
• Premature ovarian insufficiency (POI). Also described as hypergonadotropic hypogonadism, this refers to loss of ovarian activity under the age of 40, and may be due to:
  • Idiopathic early menopause (70-90% of cases of POI).
  • Genetic factors and chromosomal abnormalities.
  • Chemotherapy.
  • Radiotherapy.
  • Autoimmune disease.
  • Surgery.
• Functional hypothalamic amenorrhoea. This describes chronic anovulation resulting from hypothalamic dysfunction not due to an identifiable organic cause, but usually associated with stress, excessive exercise, and/or weight loss. An eating disorder may be involved. The female athlete triad is a medical condition observed in physically active females (such as distance runners, gymnasts, and dancers) involving low energy availability (with or without eating disorders), menstrual dysfunction, and low bone density. The definition has been broadened to include all active people and is now more commonly called 'relative energy deficiency in sport' (RED-S).
• Other hypothalamic causes, including:
  • Chronic systemic illness (such as severe cardiac, renal, or liver disease; inflammatory bowel disease; coeliac disease; AIDS; or cancer).
  • Cranial irradiation, infection or head injury.
  • Central nervous system tumours (such as craniopharyngiomas or metastases).
• Pituitary causes, including:
  • Prolactinoma and other hormone-secreting pituitary tumours.
  • Head injury and cranial irradiation.
  • Hypopituitarism (for example, after traumatic brain injury).
  • Sheehan's syndrome (pituitary infarction after major obstetric haemorrhage).
  • Sarcoidosis.
  • Tuberculosis.
• Uterine causes, including:
  • Cervical stenosis.
  • Asherman's syndrome (intrauterine adhesions).
• Polycystic ovary syndrome (multifactorial cause of amenorrhoea).
• Iatrogenic causes, including:
  • Contraceptives — extended-cycle combined oral contraceptives, injectable progesterone, implantable etonogestrel, and levonorgestrel intrauterine systems may cause amenorrhoea, as may oral progestogens that may be prescribed for that purpose .
  • Drugs (such as antipsychotics, which can cause increased prolactin levels) and illicit drug use (in particular cocaine and opiates, which can cause hypogonadism).
  • Surgery (hysterectomy, endometrial ablation, and ovarian surgery).
• Other endocrine gland disorders:
  • Thyroid disease (hypothyroidism or hyperthyroidism).
  • Uncontrolled diabetes.
  • Cushing's syndrome.
  • Adrenal insufficiency.
  • Late-onset congenital adrenal hyperplasia.
  • Androgen-secreting tumours of the ovary or adrenal gland (rare).  

The most common causes are polycystic ovary syndrome, hypothalamic dysfunction, premature ovarian insufficiency, and hyperprolactinaemia. 

[Practice Committee of the American Society for Reproductive Medicine, 2008; ESHRE, 2015; Gordon, 2017; Klein, 2019; Panay, 2020; BMJ Best Practice, 2022b]

Basis for recommendation

These recommendations are based on definitions used in the International PCOS Network (2023) International Evidence-based Guideline for the assessment and management of polycystic ovary syndrome [International PCOS Network, 2023], the reVITALize Gynecology Data Definitions [ACOG, 2018a], the American College of Obstetricians and Gynecologists Committee Opinion No 651: Menstruation in girls and adolescents [ACOG, 2015], the British Medical Journal (BMJ) Best Practice guide Assessment of primary amenorrhoea [BMJ Best Practice, 2022a], and by experts in review articles, Current evaluation of amenorrhea [Practice Committee of the American Society for Reproductive Medicine, 2008], Amenorrhea: An approach to diagnosis and management [Klein, 2019], Diagnosis and management of primary amenorrhea and female delayed puberty [Seppä, 2021], and Primary amenorrhea [Gasner, 2023].

Although some authorities define primary amenorrhoea as the failure to establish menstruation by 16 years of age in those with normal secondary sexual characteristics, or by 14 years of age in those with no secondary sexual characteristics, the majority of the literature refers to the equivalent ages of 15 and 13, and the decision to use this latter definition in these recommendations is pragmatic as it is inclusive of both definitions, and would be expected to pick up causative conditions earlier.

Interpretation of investigation findings

Referral to a specialist is likely to be needed for people with primary amenorrhoea regardless of the result of investigations, but the following information may guide referral, speed up diagnosis, and aid explanation to the person about the possible cause of amenorrhoea (pending specialist opinion).

• Pelvic ultrasound
  • Uterus present.
    • In girls with normal secondary sexual characteristics, causes include outflow obstruction (for example, imperforate hymen or transverse vaginal septum) and polycystic ovary syndrome (PCOS).
    • In girls with no secondary sexual characteristics, causes include Turner's syndrome (46XO; 'streak' ovaries only) and gonadal agenesis (46XX or 46XY).
  • Absent or abnormal uterus could be caused by androgen insensitivity syndrome.
• Prolactin levels
  • Prolactin levels greater than 1000 mIU/L usually warrant further investigation by an endocrinologist (usually magnetic resonance imaging [MRI] of the pituitary fossa is required). Causes include pituitary adenoma, empty sella syndrome, hypothyroidism, and drugs (including antipsychotics [particularly risperidone], antidepressants [particularly selective serotonin reuptake inhibitors], and antiemetics [such as metoclopramide or domperidone]).
  • Refer to local reference ranges and referral criteria for mild elevations of prolactin levels.
  • The most common causes of mild hyperprolactinaemia in primary care are stress and medications (such as antipsychotics).
  • Other causes include:
    • Pregnancy and breastfeeding.
    • Needle phobia or traumatic venesection (can double or occasionally quadruple basal prolactin concentrations).
    • Vigorous exercise within 30 minutes of the blood sample being taken.
    • PCOS (in 10–20% of people; rarely above 1000 mIU/L).
    • Renal impairment (occasionally associated with mild hyperprolactinaemia; typically less than 2000 mIU/L).
    • Hypothyroidism (uncommon, often still within the reference range and only rarely above 1200 mIU/L). 
  • Persistent moderate elevations may be due to pituitary adenomas.
• Thyroid-stimulating hormone levels
  • See the CKS topics on Hypothyroidism and Hyperthyroidism for more information.
• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
  • Consider outflow obstruction if FSH and LH levels are normal (although they can be normal in other common causes such as functional hypothalamic amenorrhoea and PCOS).
  • If secondary sexual characteristics are absent, karyotyping in secondary care may be necessary.
    • Short stature and high FSH and LH levels suggest Turner's syndrome.
    • Short stature and low FSH and LH levels suggest an intracranial lesion, for example, hydrocephalus.
    • Normal height and high FSH and LH levels suggest ovarian failure (normal karyotype) or 46XY (abnormal karyotype).
    • Normal height and low FSH and LH levels suggest constitutional delay, weight loss, anorexia nervosa, or excessive exercise.
• Total testosterone levels
  • High levels of total testosterone (refer to local laboratory reference range) warrant investigation to exclude androgen insensitivity (46XY genotype, female phenotype), late-onset congenital adrenal hyperplasia, Cushing's syndrome, or an androgen-secreting tumour.
  • A moderately increased testosterone level may be seen in PCOS.

Basis for recommendation

These recommendations are based on the American College of Obstetricians and Gynecologists Committee Opinion No 651: Menstruation in girls and adolescents [ACOG, 2015], on Functional hypothalamic amenorrhea: An Endocrine Society clinical practice guideline [Gordon, 2017], on the British Medical Journal (BMJ) Best Practice guide Assessment of primary amenorrhoea [BMJ Best Practice, 2022a], and on expert opinion in review articles, Current evaluation of amenorrhea [Practice Committee of the American Society for Reproductive Medicine, 2008], Interpreting raised prolactin results [Levy, 2014], Hyperprolactinaemia [Samperi, 2019], Amenorrhea: An approach to diagnosis and management [Klein, 2019], Where have the periods gone? The evaluation and management of functional hypothalamic amenorrhea [Gibson, 2020], Evaluation and management of amenorrhea [Pitts, 2021], Diagnosis and management of primary amenorrhea and female delayed puberty [Seppä, 2021], and Primary amenorrhea [Gasner, 2023].

Basis for recommendation

This recommendation is based on definitions of secondary amenorrhoea in the International Classification of Diseases 11th edition (ICD-11) from the World Health Organization (WHO) [WHO, 2023], the reVITALize gynecology data definitions endorsed by, among others, the American College of Obstetricians and Gynecologists, The American Society for Reproductive Medicine and the American Academy of Family Physicians [ACOG, 2018a], and on the recommendations in Functional hypothalamic amenorrhea: an Endocrine Society clinical practice guideline [Gordon, 2017], as well as expert opinion in the British Medical Journal (BMJ) Best practice guide Assessment of secondary amenorrhoea [BMJ Best Practice, 2022b], and review articles Current evaluation of amenorrhea [Practice Committee of the American Society for Reproductive Medicine, 2008], and Amenorrhea: a systematic approach to diagnosis and management [Klein, 2019].

This topic does not cover oligomenorrhoea, but of note, the Endocrine Society clinical practice guideline also recommends diagnostic evaluation for women whose menstrual cycle length persistently exceeds 45 days [Gordon, 2017].

Interpretation of investigation findings

See Table 1 for laboratory findings on the common causes of secondary amenorrhoea. 

• Follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
  • High FSH and LH levels suggest premature ovarian insufficiency (POI) in women younger than 40 years of age. Diagnosis of POI is confirmed by oligo/amenorrhoea for at least 4 months and elevated FSH (>25 IU/l) on two occasions at least 4 weeks apart.
  • Normal or low FSH and LH levels suggest hypothalamic causes (weight loss, excessive exercise, stress, or rarely, a hypothalamic or pituitary tumour).
  • Normal FSH levels and normal or moderately increased LH levels may be found in polycystic ovary syndrome (PCOS).
• Prolactin levels
  • Prolactin levels greater than 1000 mIU/L usually warrant further investigation by an endocrinologist (usually magnetic resonance imaging [MRI] of the pituitary fossa is required). Causes include pituitary adenoma, empty sella syndrome, hypothyroidism, and drugs (including antipsychotics [particularly risperidone], antidepressants [particularly selective serotonin reuptake inhibitors], and antiemetics [such as metoclopramide or domperidone]).
  • Refer to local reference ranges and referral criteria for mild elevations of prolactin.
  • The most common causes of mild hyperprolactinaemia in primary care are stress and drugs (such as antipsychotics).
  • Other causes include:
    • Pregnancy and breastfeeding.
    • Vigorous exercise in the 30 minutes before the sample is taken.
    • Needle phobia or traumatic venesection (can double or occasionally quadruple basal prolactin concentrations).
    • PCOS (in 10–20% of people; rarely above 1000 mIU/L).
    • Renal impairment (occasionally associated with mild hyperprolactinaemia; typically less than 2000 mIU/L).
    • Hypothyroidism (uncommon, often still within the reference range and only rarely above 1200 mIU/L). 
  • Persistent moderate elevations may be due to pituitary adenomas.
• Thyroid-stimulating hormone
  • See the CKS topics on Hypothyroidism and Hyperthyroidism for more information.
• Total testosterone
  • High levels of total testosterone (refer to local laboratory reference ranges) warrant investigation to exclude other causes, such as Cushing's syndrome, late-onset congenital adrenal hyperplasia, or an androgen-secreting tumour.
  • A moderately increased testosterone level or free androgen index may be seen in PCOS.
• Ultrasound scan
  • Polycystic ovaries on ultrasound are defined as the presence of 20 or more follicles in at least one ovary. See the CKS topic Polycystic ovary syndrome for further information about diagnostic criteria.

Table 1. Laboratory findings on the common causes of secondary amenorrhoea.

Basis for recommendation

These recommendations are largely based on the British Medical Journal (BMJ) Best Practice guide Assessment of secondary amenorrhoea [BMJ Best Practice, 2022b], as well as on European and international guidelines, International evidence-based guideline for the assessment and management of polycystic ovary syndrome [International PCOS Network, 2023], Functional hypothalamic amenorrhea: An Endocrine Society clinical practice guideline [Gordon, 2017], the European Society of Human Reproduction and Embryology (ESHRE) guideline on Management of women with premature ovarian insufficiency [ESHRE, 2015], and on expert opinion in review articles, Current evaluation of amenorrhea [Practice Committee of the American Society for Reproductive Medicine, 2008], Interpreting raised prolactin results [Levy, 2014], Hyperprolactinaemia [Samperi, 2019], Amenorrhea: An approach to diagnosis and management [Klein, 2019], Where have the periods gone? The evaluation and management of functional hypothalamic amenorrhea [Gibson, 2020], and Approach to the patient with new-onset secondary amenorrhea: is this primary ovarian insufficiency? [Stuenkel, 2022].

How should I manage a person with primary amenorrhoea?

• Refer those with primary amenorrhoea to secondary care for specialist investigation and, where necessary, management, of the underlying cause.
  • Refer:
    • Girls who have no secondary sexual characteristics and have not started menstruating by 13 years of age.
    • Girls with normal secondary sexual characteristics and have not started menstruating by 15 years of age.
    • Girls who have not started menstruating 3 years after thelarche (onset of breast development) or 5 years after thelarche if that occurred before the age of 10.
  • Refer at an earlier age if the girl or her parents are concerned or if an abnormality is suspected, for example, in those with:
    • Abdominal or pelvic pain.
    • Growth retardation.
    • Symptoms and signs of androgen excess (such as hirsutism) or thyroid disease.
    • Galactorrhoea.
    • Suspected genital tract malformation, intracranial tumour (for example, prolactinoma), chromosomal anomaly (for example, Turner's syndrome or androgen insensitivity).
    • Suspected eating disorder. If an eating disorder is suspected, refer immediately to a community-based, age-appropriate eating disorder service for further assessment and treatment.
  • Follow local referral pathways in determining whether to refer to paediatrics, gynaecology, or endocrinology.
    • Referral to a gynaecologist (preferably with a special interest in adolescent gynaecology) is appropriate for most girls with primary amenorrhoea.
    • Referral to an endocrinologist is recommended for girls who are not showing any secondary sexual characteristics by the age of 13, or those with hyperprolactinaemia, thyroid disease, or features of androgen excess (such as hirsutism, acne, and virilization).
• Manage amenorrhoea caused by weight loss, excessive exercise, stress, or chronic illness after an endocrinologist has assessed and excluded other hypothalamic or pituitary causes (such as chronic disease or a tumour). 
  • For weight-related amenorrhoea, encourage weight gain and refer to a specialist service if necessary, particularly if an eating disorder is suspected. See the CKS topic on Eating disorders for more information. It is likely that multidisciplinary team input will be required, including clinicians, therapists, and dieticians.
  • For exercise-related amenorrhoea, advise reducing exercise, increasing calorie intake, and weight gain. Consider referral to, or liaison with, a dietician and/or sports physician if available. Signpost to resources such as the Health 4 Performance Working Group and Project RED-S.
  • For stress-related amenorrhoea, consider measures to manage stress and improve coping strategies, such as cognitive behavioural therapy. See the CKS topics on Generalized anxiety disorder, Depression, and Depression in children for more information.
• If amenorrhoea persists for more than 6 months, consider whether osteoporosis prophylaxis is required.

How should I manage the risk of osteoporosis?

• For girls and women with hypothalamic amenorrhoea (or those with other causes of persisting amenorrhoea associated with low oestrogen levels who are at increased risk of developing osteoporosis):
  • Treat the underlying cause, if possible.
  • Assess their fragility fracture risk. See the CKS topic on Osteoporosis - prevention of fragility fractures for more information.  
  • Consider a dual-energy X-ray absorptiometry (DXA) scan to measure baseline bone mineral density in any girl considered to have had primary amenorrhoea for 6 months or more, or earlier if there is evidence of severe nutritional deficiency (liaise with the specialist involved).
  • Advise maintaining a healthy lifestyle to optimize bone health. This involves doing weight-bearing exercises, avoidance of smoking and excess alcohol, eating a balanced diet, and maintenance of normal body weight. Refer to a specialist multidisciplinary team, where an eating disorder is the cause, for support in weight restoration or maintenance.
  • Correct vitamin D deficiency and ensure an adequate calcium intake. See the CKS topic on Vitamin D deficiency in adults and Vitamin D deficiency in children for more information.  
  • Seek specialist advice regarding offering hormone replacement therapy (HRT) (off-label use) to reduce the risk of osteoporosis if amenorrhoea persists for more than 12 months, or if low bone mineral density has been confirmed on DXA scan.
    • Seek specialist paediatric or endocrinological advice before starting hormone treatment, and coordinate with the eating disorder team in cases of eating disorders.
    • Where recommended by a specialist, treatment is with transdermal oestrogen and cyclical oral progesterone. There is no evidence for the use of the oral contraceptive pill in protecting bone density.
    • Review treatment at least annually, in liaison with the specialist involved.

How should I manage secondary amenorrhoea?

• Management will be dependent on the underlying cause.
• Manage the following causes for secondary amenorrhoea in primary care in line with accepted guidelines:
  • Polycystic ovary syndrome (PCOS), when appropriate. See the CKS topic on Polycystic ovary syndrome for more information.
  • Hypothyroidism (menses may take several months to resume with treatment). See the CKS topic on Hypothyroidism for more information.
  • Menopause (women 40 years of age or older). See the CKS topic on Menopause for more information.
  • Pregnancy (usually managed by the community midwifery team). See the CKS topic on Antenatal care - uncomplicated pregnancy for more information.
• Refer all other people with secondary amenorrhoea for specialist investigation and, where appropriate, management of the cause:
  • Refer to a gynaecologist if any of the following are present:
    • Persistently elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, which suggests premature ovarian insufficiency in women younger than 40 years of age.
    • Recent history of uterine or cervical surgery (such as endometrial curettage, Caesarean section, or myomectomy) or severe pelvic infection (endometritis), which suggests Asherman's syndrome or cervical stenosis.
    • Infertility. See the CKS topic on Infertility for more information.
    • Suspected PCOS where the diagnosis is unclear or where there are complications that cannot be managed in primary care. See the CKS topic on Polycystic ovary syndrome for more information.
  • Refer to an endocrinologist if any of the following are present:
    • Hyperprolactinaemia: Refer in line with local reference ranges and referral policy. This includes those taking drugs that are known to increase prolactin levels.
    • Low FSH and LH levels (to exclude hypopituitarism or a pituitary tumour, although stress, excessive exercise, or weight loss are more likely causes).
    • An increased testosterone level that is not explained by PCOS (suggesting an androgen-secreting tumour, late-onset congenital adrenal hyperplasia, or Cushing's syndrome).
    • Other features of Cushing's syndrome or late-onset congenital adrenal hyperplasia (besides an increased testosterone level).
• Manage amenorrhoea caused by weight loss, excessive exercise, stress, or chronic illness after an endocrinologist has assessed and excluded other hypothalamic or pituitary causes (such as a tumour). 
  • For weight-related amenorrhoea, encourage weight gain and refer to a dietician if necessary. If an eating disorder is suspected, refer promptly to a specialist eating disorders service. See the CKS topic on Eating disorders for more information.
  • For exercise-related amenorrhoea, advise reducing exercise, increasing calorie intake, and weight gain. Consider referral to, or liaison with, a dietician and/or sports physician if available. Signpost to resources such as the Health 4 Performance Working Group and Project RED-S.
  • For stress-related amenorrhoea, consider measures to manage stress and improve coping strategies, such as cognitive behavioural therapy. See the CKS topics on Generalized anxiety disorder, Depression in children, and Depression for more information.
• Offer contraceptive advice to women who do not wish to become pregnant, as a small number of women with secondary amenorrhoea will become pregnant. See the CKS topic on Contraception - assessment for more information.
• Manage the risk of osteoporosis. 

How should I manage the risk of osteoporosis?

• For women with premature ovarian insufficiency (younger than 40 years of age), hypothalamic amenorrhoea, or hyperprolactinaemia (women with amenorrhoea associated with low oestrogen levels who are at increased risk of developing osteoporosis):
  • Treat the underlying cause, if possible.
  • Assess their fragility fracture risk. See the CKS topic on Osteoporosis - prevention of fragility fractures.
  • Consider a dual-energy X-ray absorptiometry (DXA) scan to measure baseline bone mineral density. Offer DXA scanning to all women diagnosed with premature ovarian insufficiency and those with amenorrhoea for more than 6 months. Consider ongoing DXA monitoring every 12 months if amenorrhoea persists, or every 2-3 years in those with premature ovarian insufficiency if low bone density has been identified and oestrogen replacement therapy is being used.
  • Advise maintaining a healthy lifestyle to optimize bone health. This involves doing weight-bearing exercises, avoidance of smoking and excess alcohol, eating a balanced diet, and maintenance of normal body weight. 
  • Correct vitamin D deficiency, and ensure an adequate calcium intake. See the CKS topic on Vitamin D deficiency in adults.
  • Seek specialist advice regarding the use of hormone replacement therapy (HRT) (off-label use) if amenorrhoea persists for more than 12 months, or on diagnosis of premature ovarian insufficiency.
    • Cyclical combined HRT (at the doses used for menopause) may be advised to reduce bone mineral density loss. Transdermal oestrogen with a cyclical oral progestogen is usually recommended, but the preparation used may vary with the cause of amenorrhoea and the need for contraception. See the CKS topic on Menopause for prescribing information.
    • Hormone treatment should be considered for those with hypothalamic amenorrhoea if non-pharmacological measures have not led to restoration of menses after 6–12 months.
    • Review treatment at least annually. For women with amenorrhoea due to reversible causes (such as weight loss or excessive exercise), oestrogen replacement should be periodically stopped (for example after 12 months of treatment, for 6 months) to see whether menses resume off treatment. Those with premature insufficiency are usually advised to continue hormone treatment until the age of natural menopause.