The physiological control of adrenal
androgen secretion has not been definitively established. However, there is evidence to suggest that a
dexamethasone-suppressible factor other than
ACTH may have a specific role to play. The majority of patients with idiopathic
hirsutism (
hirsutism associated with regular menstruation) have findings suggestive of adrenal
androgen excess, including enhanced
androgen responsiveness following administration of
metyrapone, and respond to treatment with
dexamethasone, 0.5 mg given each night. Patients with idiopathic
hirsutism have elevated
androgens but normal oestrogen and gonadotrophin levels. In contrast, while patients with
polycystic ovary syndrome (PCOS) also demonstrate evidence of adrenal
androgen excess, these patients have elevated oestrone levels and gonadotrophin secretion is abnormal. Approximately 50% of patients with PCOS treated with
dexamethasone resume regular menstruation. Oestrone excess appears to be primary to the abnormal gonadotrophin secretion and to the development of PCOS. In non-obese patients with PCOS elevated oestrone appears to occur as a consequence of the availability of the excessive amounts of its immediate precursor,
androstenedione, an
androgen mainly of adrenal origin.
Androstenedione is converted to oestrone in fat. Obese amenorrhoeic subjects have normal
androstenedione values but elevated oestrone levels with abnormal gonadotrophin secretion as seen in PCOS. These findings indicate that abnormal gonadotrophin secretion is associated with elevated oestrone levels whether these occur as a consequence of excessive adrenal
androgen secretion, or the excessive conversion of normal amounts of available
androstenedione. Patients with idiopathic
hirsutism and elevated
androstenedione levels but normal oestrone values appeared to be protected against the development of PCOS by relatively poor conversion of
androstenedione to oestrone. It is likely, therefore, that if patients with idiopathic
hirsutism gain additional adipose tissue, elevated oestrone levels will result and PCOS will develop. These observations explain the frequent association of PCOS and
obesity. There is a close clinical association between elevated
androgen levels and
hirsutism and between elevated oestrone levels and menstrual disturbances. However, some patients with amenorrhoea but without
hirsutism may demonstrate marked elevations of
androgens and oestrone, the correction of which leads to the resumption of regular ovulation. This presentation, 'amenorrhoea with cryptic hyperandrogenaemia', is probably explained by diminished sensitivity of
androgen receptors.(ABSTRACT TRUNCATED AT 400 WORDS)