The impact of a 3-month continuous administration of transdermal estradiol (E2-TTS 50; 50 micrograms/day) or oral conjugated estrogen (CE; 0.625 mg/day) on glucose and lipid metabolism was investigated in two groups (n = 15/group) of postmenopausal women. Fasting levels of glucose, insulin, and C-peptide; C-peptide/insulin ratio (index of hepatic insulin clearance); and their responses to a 75-g oral glucose tolerance test (OGTT) were evaluated before and after 3 months of continuous estrogen administration. E2-TTS 50 modified carbohydrate metabolism, decreasing fasting insulin levels (P less than 0.01) and increasing the pancreatic islet response to glucose challenges, as indicated by an increased integrated value of the C-peptide curve associated with OGTT (P less than 0.05). Despite greater C-peptide secretion, integrated peripheral insulin after OGTT was decreased (P less than 0.05). The resulting increase in the integrated curve of the molar C-peptide/insulin ratio (P less than 0.01) indicated elevated hepatic insulin clearance after E2-TTS 50 administration. CE treatment did not modify carbohydrate metabolism, except for reducing fasting glucose levels (P less than 0.01). Neither therapy modified lipid metabolism, but a slight increase in circulating triglycerides (P less than 0.01) was observed during CE administration. Our data show that the addition of low doses of natural estrogens does not negatively influence glucose and lipid metabolism in postmenopausal women. By contrast, reversal of postmenopausal hypoestrogenism to early follicular phase estrogenic values with E2-TTS 50 administration seems to exert a beneficial effect on glucose metabolism by increasing hepatic insulin clearance.
To evaluate whether ovarian steroid environment may modify endogenous opioid activity at hypothalamic-pituitary level, the effects of naloxone infusion (1.2 mg/h for 4 h) on gonadotropin secretion were studied in 5 postmenopausal women who had natural menopause 3–5 years before the study. In addition, naloxone infusion was repeated in the same subjects after chronic oral treatment with conjugated estrogens (1.25 mg/day in two divided doses for 20 days). Before treatment, both the circulating levels of estrogens and plasma gonadotropins were in the normal range for postmenopausal women and naloxone infusion did not induce any significant modification of gonadotropin secretion. In contrast, after estrogen therapy, and the consequent rise in estrogen plasma levels, naloxone infusion induced a significant LH increase (p < 0.01) starting during the last hour of treatment. These findings seem to confirm that endogenous opioid peptides may modulate the inhibitory effect exerted by estrogens on LH secretion, in humans.
Two different single doses (400 and 600 micrograms) of the new long-acting dopamine agonist cabergoline (CBG) were given to 12 normal cycling women, 17 puerperal women, and 24 hyperprolactinemic women (12 with idiopathic hyperprolactinemia and 12 with pituitary adenoma). Plasma PRL was determined in blood samples collected before and at frequent intervals for 5 days after CBG administration. Both CBG doses induced marked inhibition of PRL secretion in all women. A decrease in plasma PRL levels was evident 1-2 h after CBG administration and persisted for up to 5 days. The 600-micrograms CBG dose had a more potent (P less than 0.05) PRL inhibitory effect than the 400-micrograms dose in normal, puerperal, and hyperprolactinemic women. Moreover, while 400 micrograms CBG prevented lactation in 3 of 7 puerperal women, 600 micrograms CBG prevented lactation in 5 of 5 puerperal women. A moderate blood pressure decrease occurred 3-6 h after CBG treatment, but no other side-effects occurred. These results demonstrate that CBG induces a dose-related inhibition of PRL secretion in normal women as well as in puerperal and hyperprolactinemic women. The potent long-lasting PRL inhibitory effect of CBG in conjunction with the absence of side-effects typical of dopaminergic compounds suggest that this drug is an advance in the medical treatment of hyperprolactinemia.
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