Androgens in relationship to cardiovascular risk factors in the menopausal transition.

OBJECTIVE: To establish the relationship between androgens and cardiovascular disease (CVD) risk factors in the menopausal transition. METHODS: A total of 124 women were divided into four groups: 29 premenopausal (PreM), 35 women in the menopausal transition still menstruating (MTM), 29 women in the menopausal transition with 3-6 months amenorrhea (MTA), and 31 postmenopausal women (PostM). Levels of triglycerides, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, glucose and insulin were assayed in all samples and waist circumference was measured. In a subgroup of 83 women (19 PreM, 21 MTM, 28 MTA and 15 PostM), levels of total testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS) and estradiol were determined. The free androgen index, Homeostasis Model Assessment (HOMA) index, Quantitative Insulin Sensitivity Check Index (QUICKI) and McAuley index, estradiol/total testosterone and triglyceride/HDL cholesterol ratios were calculated. RESULTS: Androstenedione was higher in MTA vs. PostM women (p < 0.05); DHEAS was higher in PreM women vs. the other three groups (p < 0.05). Sex hormone binding globulin (SHBG) in MTM women was higher than in MTA women (p < 0.05); the free androgen index was lower in MTM women than in MTA and PostM women. SHBG and the free androgen index showed negative and positive correlations, respectively with waist circumference, insulin resistance and lipids. In a multiple regression analysis, considering waist circumference, neither free androgen index nor SHBG showed significant differences between groups. The waist circumference correlated only with SHBG (p = 0.022) and correlations between SHBG and insulin resistance markers continued to be significant, but relationships between SHBG and lipoproteins and all correlations found with free androgen index were lost. CONCLUSIONS: An increment in the androgenic milieu that correlates with abdominal fat, insulin resistance and atherogenic lipoproteins becomes evident after the menopausal transition and suggests that evaluation of cardiovascular disease risk in these women should include androgens, considering that abdominal obesity is one of the main determinants of the relationship between androgenic parameters and cardiovascular risk factors.

Metabolic syndrome throughout the menopausal transition: influence of age and menopausal status.

OBJECTIVE: To assess the relationship between the main components of both the metabolic syndrome and insulin resistance and menopausal status in the menopausal transition. METHODS: A total of 124 healthy women were divided into four groups according to their menstrual status: the first group consisted of 35 women in menopausal transition with menstrual bleeding (MTM) and with cycles between 35 and 80 days; the second group was composed of 29 women in menopausal transition with 3-6 months of amenorrhea (MTA). The third group consisted of 31 postmenopausal women (PostM) and the fourth group of 29 premenopausal women (PreM) with regular cycles. The metabolic syndrome was evaluated following the ATP III criteria. Evaluation of insulin resistance was made through the HOMA, QUICKI and McAuley indices and the triglycerides/high density lipoprotein (HDL) cholesterol ratio. RESULTS: The triglycerides/HDL cholesterol ratio increased in MTM, MTA and PostM women in comparison with PreM women. A slight decrease in the QUIKI index (p = 0.06) and a decrease in the McAuley index (p < 0.001) were observed in MTM, MTA and PostM women in comparison to PreM women. The relative frequencies of metabolic syndrome in the four groups were: PreM, 0%; MTM, 20%; MTA, 21%; and PostM, 22% (p = 0.0001). The most frequent markers of the metabolic syndrome were increased waist circumference, low HDL cholesterol levels and hypertension. Linear regression between menopausal status and metabolic syndrome was lost when age was added to the model. CONCLUSIONS: The frequency of metabolic syndrome increased from the time of the menopausal transition to the postmenopause. Abdominal obesity was the most frequent feature observed. Nevertheless, aging erased the effect of the menopause on the metabolic syndrome. In order to prevent cardiovascular disease, the metabolic syndrome must be evaluated from the time of the menopausal transition.

Once and twice a week transdermal estradiol delivery systems: clinical efficacy and plasma estrogen levels.

We compared the clinical efficacy and circulating estrogen levels from two transdermal delivery systems, 'drug-in-adhesive' type, in 20 healthy postmenopausal women. Both patches, developed by Beta Pharmaceutical Laboratories in Argentina, deliver estradiol at a rate of 50 micrograms/day; the replacement frequency of system A (TrialSat) was twice a week and for system B (TrialSat LA) once a week. The women were treated for 180 days, in a continuous regimen, with additional oral medroxyprogesterone acetate 5 mg/day for 14 days of each cycle. Blood samples were taken at the end of the wearing period: the 3rd day for Group A and the 7th day for Group B, to determine levels of estradiol, estrone, non-sex hormone binding globulin (SHBG)-bound estradiol and SHBG. Both treatments had similar clinical efficacy and were well tolerated. Plasma estradiol levels were higher in Group A throughout the study, probably owing to the different sampling times. SHBG and non-SHBG-bound estradiol were unchanged in both groups. As there was a similar performance of both delivery systems, the 7-day patch may be preferable, and produce greater compliance.

A comparative study of two hormone replacement therapy regimens on safety and efficacy variables.

OBJECTIVE: To assess the effect of tibolone on endometrial safety, plasma estradiol concentrations, lipid metabolism and climacteric symptoms in comparison to sequential conjugated equine estrogens and medroxyprogesterone acetate in postmenopausal women. METHODS: In a randomised, open-label, 6-cycle, group-comparative study, the effects on the aforementioned parameters were studied with tibolone 2.5 mg/day (N = 13) continuously, and with conjugated equine estrogens 0.625 mg/day continuously, combined with medroxyprogesterone acetate 5 mg/day (N = 11) (CEE/MPA) sequentially, during 12 days of each 28-day cycle. Within-group statistical analysis was performed with Student's t-test for paired samples, whereas between-group statistics were performed using the Student's t-test for independent groups. RESULTS: Cytological evaluation revealed no endometrial stimulation in either group. In the tibolone group, there were no effects on estradiol levels, whereas in the CEE/MPA group, an increase in total and non-SHBG-bound estradiol plasma levels was reported. In the tibolone group, there were significant decreases in plasma total cholesterol, triglycerides, HDL-cholesterol and VLDL-cholesterol, whereas no significant changes in LDL-cholesterol and IDL-cholesterol were reported. In the CEE/MPA group there were significant decreases in plasma total cholesterol, HDL-cholesterol and LDL-cholesterol, whereas there were no significant changes in triglycerides, IDL-cholesterol and VLDL-cholesterol. Climacteric symptoms, particularly vasomotor episodes, decreased similarly in both groups. CONCLUSIONS: Both tibolone and CEE/MPA were safe with respect to effects on the endometrium and both treatments induced changes in the plasma profiles of certain lipid and lipoprotein parameters. However, the overall clinical implications of these changes are unknown. Finally, both regimens were equally effective in the treatment of climacteric symptoms.

Effect of melatonin on the luteinizing hormone release induced by clomiphene and luteinizing hormone-releasing hormone.

The effect of melatonin on the LH-release response after the administration of synthetic LH-RH and clomiphene citrate was investigated in adult male rats. The sc administration of melatonin (1 mg/day) for 6 days produced a significant decrease in serum LH levels and in seminal vesicles and ventral prostate weights. On the other hand, the daily injection of 0.01 mg/100 g of body weight of clomiphene citrate during 6 days significantly stimulated LH levels and the weights of the accessory sex glands. Simultaneous treatment with melatonin and clomiphene produced an inhibitory effect similar to that obtained with melatonin alone. Neither pretreatment with melatonin alone. Neither pretreatment with melatonin (1 mg/day, sc for 6 days) nor its simultaneous iv administration (500 mug) with 75 ng of LH-RH modified the LH-release in response to the hypothalamic hormone. The fact that melatonin was able to suppress the effect of clomiphene, which is probably exerted at the hypothalamic level, but not the actiion of LH-RH on the pituitary, appears to indicate that the hypothalamus may be the site involved in the inhibitory effect of the pineal principle on the reproductive function.