Amenorrhoea & Infertility

Primary Amenorrhoea

• Consider evaluation if no menses by age 15 with normal secondary sexual development or by age 13 without secondary sexual characteristics

• Differential diagnoses include constitutional delay, Müllerian agenesis, androgen insensitivity syndrome, imperforate hymen and hypogonadotrophic hypogonadism

• A detailed history should include family pubertal timing and any history of endocrine disorders

Secondary Amenorrhoea

• Common causes include polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhoea due to stress, weight loss or excessive exercise, and hyperprolactinaemia

• Other aetiologies encompass thyroid dysfunction, premature ovarian insufficiency and iatrogenic causes such as medications

• History should assess changes in menstrual pattern and associated systemic or psychosocial symptoms

Investigations for Amenorrhoea

• Exclude pregnancy with a Beta-hCG test

• Hormonal evaluation: Measure FSH, LH, estradiol, prolactin and TSH to distinguish between hypogonadotrophic and hypergonadotrophic states

• Bone age assessment via wrist X-ray to assess skeletal maturation

• Pelvic ultrasound to evaluate uterine and ovarian anatomy; transvaginal ultrasound provides superior detail if acceptable

• Consider GnRH stimulation testing to differentiate central from peripheral causes

• Chromosome analysis is indicated for suspected genetic causes such as Turner syndrome or androgen insensitivity syndrome

Infertility Differential Diagnoses

Ovulatory disorders:

• PCOS characterised by hyperandrogenism and chronic anovulation

• Premature ovarian insufficiency indicated by elevated FSH and low oestradiol

Tubal factors:

• History of pelvic inflammatory disease leading to tubal occlusion

• Endometriosis causing peritubal adhesions

Uterine factors:

• Structural abnormalities such as fibroids (especially submucosal) or congenital anomalies impairing implantation

Male factors:

• Semen abnormalities including oligospermia and asthenozoospermia should be evaluated via semen analysis

Investigations for Infertility

Ovulation assessment:

• Mid-luteal progesterone measurement to confirm ovulation

Ovarian reserve testing:

• Anti-Müllerian hormone (AMH) levels and antral follicle count by ultrasound

Tubal patency:

• Hysterosalpingography (HSG) to detect tubal occlusion

Evaluation of the male partner:

• Semen analysis following 2–3 days of abstinence

Management

• Address underlying causes of amenorrhoea:

  • Central amenorrhoea managed with GnRH analogues to delay premature pubertal progression

  • For secondary amenorrhoea, treat conditions such as thyroid dysfunction, hyperprolactinaemia or PCOS with appropriate medical therapy and lifestyle modifications

• Infertility management:

  • Ovulatory disorders may be treated with ovulation induction agents and, in PCOS, with combined oral contraceptives or insulin sensitisers

  • Anatomical causes (eg, tubal or uterine factors) may require surgical intervention

  • Evaluate both partners comprehensively to guide treatment planning and optimise fertility outcomes

Notes:

• Early evaluation and intervention are essential to prevent long-term complications such as premature epiphyseal closure in amenorrhoea and to optimise fertility outcomes

• A detailed history, including parental heights, family pubertal timing and psychosocial factors, is critical for distinguishing between normal variants and pathological conditions

• Regular monitoring of growth, bone age, and pubertal progression, as well as ongoing assessment of menstrual patterns, informs clinical management

• A multidisciplinary approach involving endocrinologists, gynaecologists, fertility specialists and mental health professionals is recommended for complex cases

• In cases of infertility, timely investigation of both partners facilitates targeted therapy and improves chances of conception

• Lifestyle modifications, including nutritional support and stress management, play a crucial role in managing functional hypothalamic amenorrhoea and improving fertility outcomes