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Stem
A 27-year-old nulliparous woman presents to her general practitioner with absent menstrual periods for nine months. Menarche was at age 13 and her cycles had previously been regular (every 28 to 30 days). She is sexually active and uses condoms. She runs competitively, training 80 to 90 km per week, and has lost 7 kg over the last year (BMI now 17.4). She reports no headaches, visual change, galactorrhoea, hot flushes, hirsutism or acne. She is mildly fatigued and has had one stress fracture of the metatarsal in the last six months. She is not taking any regular medication.
Investigations: urine beta-hCG negative. Serum FSH 3.5 IU/L, LH 2.8 IU/L, oestradiol 70 pmol/L (low), prolactin 360 mU/L (normal), TSH 1.8 mU/L (normal), testosterone 1.1 nmol/L (normal). Pelvic ultrasound: normal uterus and ovaries.
Questions
a) What is the most likely diagnosis, and which three features in the stem and investigations support it? (3 marks)
b) Outline the pathophysiology of this condition. (2 marks)
c) Outline the management. (3 marks)
d) What is the principal long-term complication if this is left untreated, and which investigation should be considered? (2 marks)
Model answers
a) Functional (hypothalamic) amenorrhoea secondary to low energy availability from high-volume endurance training and weight loss. Three supporting features: (i) low or inappropriately normal FSH and LH with a LOW oestradiol (central, hypoestrogenic pattern); (ii) negative pregnancy test with normal prolactin, TSH and testosterone, excluding the other major causes of secondary amenorrhoea; (iii) a clear precipitant — high training load (80 to 90 km per week) with a 7 kg weight loss and BMI 17.4, plus a stress fracture consistent with low bone mineral density. The triad of low energy availability (with or without disordered eating), menstrual dysfunction and low bone mineral density is the female athlete triad / RED-S.
b) Low energy availability (energy expenditure from exercise exceeding caloric intake) suppresses pulsatile gonadotrophin-releasing hormone (GnRH) release from the hypothalamic arcuate nucleus. Reduced GnRH pulse frequency lowers pituitary FSH and LH secretion, so follicular development and ovarian oestradiol production fall, abolishing the cyclic oestrogen and progesterone signals that drive endometrial proliferation and withdrawal bleeding. The resulting hypoestrogenism also removes oestrogen's restraint on bone resorption, causing bone loss.
c) (1) Energy restoration is first-line and primary — increase caloric intake, reduce training volume, and aim for weight gain (a gain of roughly 2 to 3 kg often restores cycles). (2) Address the eating behaviour / psychology — multidisciplinary input (sports physician or eating-disorder team, dietitian, psychologist; cognitive behavioural therapy has evidence). (3) If menses do not resume after 8 to 12 months of adequate lifestyle change, the Endocrine Society 2017 guideline recommends physiological HRT (transdermal oestradiol plus cyclic oral progestogen) to protect bone — the combined oral contraceptive pill does NOT restore bone mineral density in functional hypothalamic amenorrhoea and should not be relied upon. (4) Treat associated deficiencies (calcium, vitamin D) and screen for and manage an eating disorder and low bone density. (5) Counsel that fertility can usually be restored with energy recovery, but ovulation induction is withheld until weight and health are restored.
d) Osteoporosis with increased fracture risk is the principal long-term complication of untreated hypoestrogenic amenorrhoea; bone loss may be only partially reversible. A DEXA (DXA) scan to assess bone mineral density should be considered (especially with a history of stress fracture or amenorrhoea over 6 to 12 months).