Endocrine Abstracts

Background: Functional hypothalamic amenorrhoea (FHA) is a common cause of secondary amenorrhoea and is related to a combination of weight-loss, exercise and psychological stressors. These factors lead to suppression of pulsatile GnRH secretion. Diminished LH and FSH concentrations result in a hypoestrogenic state. We present an archetypal case of FHA that clearly demonstrates the ‘hypothalamic set-point’ for the body composition of a young woman below which she has profound biochemical hypogonadotrophic hypogonadism and amenorrhoea.

Case: A 19 year old Caucasian woman was referred with a 6 month history of secondary amenorrhoea. She had normal pubertal development with menarche at 12 and thelarche at 13. She reported ‘irregular periods’ for several years with cycles between 28 and 47 days. Her current BMI was 17.6 with weight loss of 6–8 kg over the preceding 12 months. The patient reported an intense exercise regimen including 90 minutes cycling 5–6 days a week and 45 minutes swimming biweekly. Physical examination was unremarkable with development at tanner stage 5 and no clinical features of hyperandrogenism.

Investigations: FSH 4.1 IU/l, LH 0.4 IU/l, Oestradiol 29 pmol/l [98–571 pmol/l], Testosterone 0.7 nmol/l [0.2–2.9], prolactin 78 mIU/l [40–485], SHBG 159 nmol/l [30–100], TSH 0.51 mU/l [0.35–3.50] and FT4 13 pmol/l [8–21]. MRI pituitary showed no structural abnormality. A progesterone challenge was undertaken with Norethisterone 5 mg TDS for 5 days. The challenge was negative with no withdrawal bleeding.

Progress: The patient was advised to gain weight resulting in an improvement of her BMI to 20.4 over the following 12 months but without return of spontaneous menses. The patient opted to defer any form of oestrogen replacement despite the risk of skeletal fragility. Further weight gain over the next 5 months lead to an improved Oestradiol of 92 pmol/l. Achieving a BMI of 21 resulted in a regular 28 day cycle.

Conclusions: FHA is a diagnosis of exclusion; once structural pituitary lesions, systemic disease and other endocrinopathies have been excluded. FHA is known to be more prevalent amongst female athletes undertaking endurance sports. A detailed diet and exercise history is required. Balancing the risks from a prolonged hypoestrogenic state against attempts to restore menses naturally via intentional weight gain can be very challenging. Unfortunately, the patient was unable to maintain her weight gain. Her BMI has fallen back to 18 and she is amenorrheic again.