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Female Reproduction: V Pathophysiology


Female Reproduction: V Pathophysiology
Clinical scenario
A 19-year-old history student, CV, presented to her university health centre requesting oral contraception. The GP noticed that she appeared very thin and enquired about her menstrual history. CV explained that her periods started when she was 15 and although she had regular cycles for about 1 year, during her time in the 6th form they had become very intermittent and had finally stopped altogether when she was 17. She was conscious of her appearance and liked being thin. She had started running for exercise during her schooldays and generally ran 10 miles four or five times a week and went to the gym several times weekly. On examination her body mass index was 16.5 kg/m2. She had normal secondary sexual characteristics and there were no other abnormal physical findings. Biochemistry showed LH 1.2 U/L, FSH 0.9 U/L, estradiol 54 nmol/L and prolactin 235 mU/L. A diagnosis of hypothalamic amenorrhoea associated with low weight and excessive exercise was made. After discussion she agreed to try and gain weight and 1 year later her body mass index was 20.5 kg/m2 and her periods had resumed.


Female Reproduction: V Pathophysiology, Reproductive pathophysiology, Primary amenorrhoea, Secondary amenorrhoea, Hypothalamic amenorrhoea, Polycystic ovary syndrome,

Reproductive pathophysiology
Disorders of reproductive function in females present with menstrual irregularity (Table 29.1).
Primary amenorrhoea and delayed puberty should always be investigated as in the majority of cases a serious underlying cause will be found and must be treated (Table 29.2).
Secondary amenorrhoea. There are a number of causes of secondary amenorrhoea (Table 29.3), all of which rarely present as primary amenorrhoea. In all cases, careful history and examination is essential, combined with appropriate endocrine inves- tigations to establish the cause. Patients with primary ovarian failure may have a history of other autoimmune disorders or of previous therapy for malignant disease. Patients with prolactinomas usually present with associated features of prolactin excess, such as galactorrhoea.

Hypothalamic amenorrhoea. The term ‘functional disorders’ is used to describe a group of conditions in which there are no structural or endocrine synthetic abnormalities in the pituitary–ovarian axis. Hypothalamic amenorrhoea is usually associated with weight-reducing diets, often with excess exercise in an attempt to remain slim, and is seen in athletes, in subjects with anorexia nervosa and in other forms of stress, either physical or psychological in origin. It is the commonest cause of secondary amenorrhoea seen in endocrine clinics.
Although a reduction in weight to 10% below ideal body weight is usually associated with amenorrhoea, there is wide variation between women. Changes in body composition, particularly reduced fat mass, are crucial to the characteristic hypothalamic changes of impaired GnRH secretion, loss of gonadotrophin pulsatility and subsequent hypogonadotrophic hypogonadism (Fig. 29a).
The treatment of weight-and exercise-related amenorrhoea is specifically weight gain and reduction in exercise. These measures restore normal ovulatory cycles and reproductive potential but may require lengthy treatment with a multidisciplinary team of endocrinologists, dieticians and psychologists. Untreated, hypothalamic amenorrhoea is associated with reduced bone mineral density and ultimately osteoporosis. Women with long-term hypoestrogenaemia should have their bone density recorded and, if there is significant osteopaenia or osteoporosis, combined estrogen/progesterone replacement therapy should be considered.

Polycystic ovary syndrome. Patients with polycystic ovary syndrome (PCOS) or non-classical congenital adrenal hyperplasia usually present with oligomenorrhoea and other signs of androgen excess (Chapter 26). Treatment is aimed at the symptoms of hyperandrogenaemia and restoring ovulatory menstrual cycles where fertility is the goal. Women with PCOS may also demonstrate other features of hyperinsulinaemia, including obesity and low HDL-cholesterol levels. In the long term, the risks of Type 2 diabetes and cardiovascular disease are increased and weight reduction and exercise play an important role in the clinical management of these patients.

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