Endocrine Abstracts

Functional hypothalamic amenorrhoea (FHA) is an endocrine disorder secondary to a deficiency of pulsatile gonadatrophin-releasing hormone (GnRH) secretion. It is not related to hypothalamus-pituitary organic lesions, endocrine or systemic disease. The clinical profile is dependant on the degree of GnRH suppression – it can range from an inadequate luteal phase to hypothalamic amenorrhoea. The incidence of FHA ranges from 15% to 48% of the secondary amenorrheas. We present the case of a 21-year-old female of Romanian origin referred to clinic with amenorrhoea. She attained menarche between the ages of 11–13 years and had regular periods for a year. After this time, her periods became more irregular and this was thought to be secondary to weight gain. The patient subsequently lost around 3–4 kg but continued to suffer from oligomenorrhoea (less than 4 cycles per year). In 2013/14 she was amenorrhoeic for one year at which time she was started on the oral contraceptive pill. This was discontinued after a year due to intolerable side effects. In 2016, she had 4 periods. There was no history of galactorrhoea, hirsutism or hot flushes. The patient was anxious about a familial cause for her symptoms as her sister also struggled with fertility issues. When reviewed in clinic, she was asymptomatic with a stable weight 58.3 kg and blood pressure 107/74 mmHg. Clinical examination was unremarkable. Blood tests showed low follicle stimulating hormone (FSH) (<1 IU/L), low luteinising hormone (LH) (<1 IU/L), oestradiol <44 pmol/l, normal prolactin (155 mIU/L), testosterone (0.8 nmol/L, sex hormone binding globulin 68 nmol/l, dehydroepiandrosterone 5 micromol/L, androstenedione 2.2 nmol/L, free thyroxine (T4) 14.6 pmol/L, thyroid stimulating hormone 1.23 mIU/L, cortisol 233 nmol/L, adrenocorticotrophic hormone 14.1 pg/mL and insulin-like growth factor 1 (IGF-1) 17.5 nmol/l. In addition, her full blood count, renal function and liver function were within normal range. A pituitary MRI showed no abnormality and transvaginal ultrasound showed normal ovaries with follicles measuring between 2–4 mm. She is awaiting a dual-energy X-ray absorptiometry (DEXA) scan. Her results were in keeping with a diagnosis of functional hypothalamic amenorrhoea. She was given life-style advice, offered psychology review for stress management and started on short-term treatment with transdermal oestrogen patches and cyclical oral progesterone (as per the Endocrine Society Clinical Practice Guideline, 2017) to protect bone health. Functional Hypothalamic Amenorrhoea is a form of chronic anovulation not due to identifiable organic causes. There is a functional reduction in GnRH drive which causes reduced LH pulsatility. The mechanisms responsible for FHA are yet to be definitively determined. Recent research indicates a role for hypothalamic neuromodulatory signalling pathways mediated by kisspeptin, a family of peptides stimulating GnRH secretion. Loss of kisspeptin signalling is associated with hypogonadotrophic hypogonadism. FHA is often associated with stress, weight loss, excessive exercise or a combination of these. It remains a diagnosis of exclusion requiring a comprehensive assessment of both systemic and endocrinologic aetiologies. Long term complications such as bone loss and infertility need to be addressed. Oral contraceptive pills (OCPs) have not shown any benefit for improving bone mineral density. On the other hand, transdermal oestrogen showed an improvement in the bone mineral density. In patients wishing to conceive, treatment with pulsatile GnRH is first line. A multidisciplinary approach is necessary and includes medical, nutritional and psychological support.