Symptoms related to the menopause and sex steroid treatments.

In the menopause transition, ovarian steroid production is gradually inhibited and around 35% of women will seek medical help for postmenopausal symptoms. The hot flush is a characteristic manifestation occurring in about 70% of women; it is associated with oestrogen withdrawal and disappears with oestrogen-based hormone replacement therapy. The exact mechanism behind it is still unclear but is probably related to heat loss mechanisms. The flush often occurs in parallel to changes in skin temperature, blood flow, pulse rate and pulses of luteinizing hormone (LH). These are probably secondary to a disturbance in the thermoregulatory centre of the CNS, which is anatomically close to neurons containing gonadotropin-releasing hormone. Depression is no more frequent in the menopausal transition than at other times in life. After surgical menopause, however, oestrogen improves low mood over placebo. In women with premenstrual syndrome, an increased feeling of well-being is associated with the pre-ovulatory oestrogen peak. Progestogens are associated with negative mood changes during the menstrual cycle, oral contraception and postmenopausal replacement therapy. Certain progesterone metabolites are anaesthetic and have anti-epileptic and anxiolytic properties, effects which are mediated via the type A gamma-aminobutyric acid (GABAA) receptor. Oestrogen is associated with increased sensory perception, locomotory activity, limb coordination and balance: this may help explain the increased frequency of bone fractures in the early postmenopausal period. Oestrogen improves memory and performance in patients with mild Alzheimer's dementia and increases epileptic activity in patients with partial epilepsy. These effects can be related to amplifying effects of oestrogen on excitatory amino acids in the CNS.