Endocrine Abstracts

Case: A 25-year-old female presented with primary amenorrhoea and a complex history. Puberty and breast development began age 11, but she did not have menarche. At age 15 she was investigated by gynaecology, and diagnosed with having polycystic ovaries, but was told she did not have PCOS. She also had a history of anxiety and anorexia nervosa from ages 15 to 20, during which, at times, she consumed less than 1200 kcal/day and her BMI dropped to 17 kg/m². She was managed for anxiety from age 15 to 20. From age 19 to 22 she used a contraceptive implant in the arm. On presentation, she was at a healthy weight (62 kg, BMI 23.9 kg/m²), no longer had an eating disorder, had a Tanner Stage 4/5 and had a normal Ferriman-Gallwey score. Initial workup showed normal gonadotropin levels (FSH 7.2 IU/l, LH 17.2 IU/l) and oestradiol (230 pmol/l), which did not suggest primary ovarian insufficiency or ongoing hypogonadotropic hypogonadism. Her progesterone level was 0.5 nmol/l, and testosterone was 2.1 nmol/l, with an AMH of 65.9 pmol/l. Ultrasound confirmed polycystic ovaries (>20 follicles per ovary) with an endometrial thickness of 7.4 mm. A DXA scan showed her bone density was within the expected range for her age, with Z-scores of -0.5 (lumbar spine) and -1.8 (femoral neck). Adrenal cortex antibodies were negative, and anti-Tg was 30 IU/mL. Genomic analysis ruled out FMR1 gene expansion and karyotyping was normal. A progesterone withdrawal test was administered to assess endometrial and ovarian function, resulting in a seven-day bleed. The positive response indicated a functional hypothalamic-pituitary-gonadal axis and a receptive endometrial lining.

Discussion: The aetiology of her amenorrhoea is likely multifactorial. A positive progesterone challenge, together with the presence of polycystic ovaries and amenorrhoea/anovulation, fulfils the Rotterdam criteria for PCOS. At the same time, her history is also consistent with hypothalamic amenorrhoea related to her eating disorder. It is likely that dysregulated hypothalamic–pituitary–ovarian signalling and asynchronous FSH/lH secretion in PCOS contributed to anovulation, which was further compounded by hypothalamic suppression. The positive response to the progesterone challenge and her preserved bone mineral density suggest a favourable prognosis.