Female Reproduction Pathophysiology
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.
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.
