Percutaneous 17 beta-estradiol replacement therapy in hypertensive postmenopausal women.

The present study evaluated the short-term effects of percutaneous 17 beta-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17 beta-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administration. Systolic and diastolic blood pressure or heart rate did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued). Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins) also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 +/- 27.21 to 35.09 +/- 20.44 IU/l, P < 0.05), and an increase in estradiol levels (15.06 +/- 8.76 to 78.7 +/- 44.6 pg/ml, P < 0.05). There was no effect on LH (18.0 +/- 9.5 to 14.05 +/- 8.28 IU/l). Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17 beta-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women.

Estrogen receptor 2 and progesterone receptor gene polymorphisms and lipid levels in women with different hormonal status.

Sex steroid hormones have multiple effects on lipid metabolism. We investigated the association between two common single nucleotide polymorphisms of the estrogen receptor 2 gene (ESR2), 1082G>A and 1730A>G, and PROGINS polymorphism of the progesterone receptor gene (PGR) with lipoprotein levels in a cross-sectional study with 472 women of European descent. The women were classified into three subgroups according to hormonal status, premenopausal women (n=187; mean age=34+/-9.7 years), postmenopausal women exposed to hormone replacement therapy (HRT) (n=118; 56+/-6.7 years) and postmenopausal women unexposed to HRT (n=167; 58+/-9.8 years). The premenopausal and postmenopausal women exposed to HRT, both carriers of G/A genotype, exhibited LDL-C (P=0.027 and 0.001, respectively) and T-chol levels (P=0.035 and 0.001, respectively) lower than carriers of G/G genotype. This association was not observed in postmenopausal women unexposed to HRT. These results suggest that ESR2 1082G>A genotype may influence LDL-C levels in women with abundant estrogen levels, due to either endogenous or exogenous sources.

Estrogen-metabolizing gene polymorphisms and lipid levels in women with different hormonal status.

Endogenous and exogenous sex steroid hormones have multiple effects on lipid and lipoprotein metabolism. It is also known that estrogen has antiatherogenic actions, therefore we considered examining whether there was any association between polymorphisms in estrogen-metabolizing genes and lipid levels in women. We investigated the association between variants in genes related to estrogen biosynthesis (CYP19-TTTA(n)) and estrogen catabolism (CYP1A1*2A, CYP1A1*2C, CYP1A2-Asn516Asn, CYP3A4*1B, and COMT-Val158Met) with serum lipid levels in a cross-sectional study with 472 Brazilian women of European descent. They were divided into three subgroups according to their hormonal status: premenopausal women (n=187), postmenopausal women exposed to hormonal replacement therapy (HRT) (n=118), and postmenopausal women unexposed to HRT (n=167). The postmenopausal women receiving HRT who were carriers of the CYP3A4*1B variant showed lower low-density lipoprotein cholesterol levels than wild-type homozygotes. Premenopausal women homozygous for the CYP1A1*2C allele had higher high-density lipoprotein cholesterol levels than heterozygotes. While the CYP1A1*2C variant probably has a higher catalytic activity, the functional implications of the CYP3A4 polymorphism are still uncertain. These data are the first attempt to associate estrogen metabolism genes to lipid levels in women.

Endometrial response to a cyclic regimen of percutaneous 17beta-estradiol and low-dose vaginal micronized progesterone in women with mild-to-moderate hypertension.

Endometrial response to natural estradiol and low-dose vaginal progesterone replacement therapy was evaluated in 20 postmenopausal women with chronic, mild-to-moderate hypertension. A cyclic hormone replacement therapy (HRT) regimen was used (21/28 days) with percutaneous estradiol (1.5 mg/day) and vaginal micronized progesterone (100 mg/day). Menopausal symptoms decreased and estradiol concentrations increased substantially and remained in the physiological range throughout treatment. Serum gonadotropin concentrations decreased significantly (p < 0.001, Friedman's ANOVA). Bone mineral density increased by 2.1% (p = 0.029) only at the lumbar spine. Endometrial thickness remained unchanged. Breakthrough bleeding or spotting occurred in 18% of cycles in the first 3 months of HRT, 30% in months 4-9 and 22% in months 10-12. Withdrawal bleeding occurred in 40% of cycles in the first 3 months and decreased to 25% in months 10-12. At month 12, there were 11 women with amenorrhea due to endometrial atrophy. Nine women had active endometria (proliferative or secretory) and thus reported vaginal bleeding. No severe bleeding, hyperplasia, or carcinoma was found. Vaginal bleeding was tolerated, and no subject withdrew from the study. Results suggest that this regimen confers endometrial protection and is well tolerated, and can therefore safely be used for at least 1 year by postmenopausal women with hypertension and menopausal symptoms.

Percutaneous 17 beta-estradiol replacement therapy in hypertensive postmenopausal women

The present study evaluated the short-term effects of percutaneous 17Beta-estradiol on blood pressure, metabolic profile and hormonal levels in postmenopausal women with systemic arterial hypertension. After a wash-out period of 15 days, 10 hypertensive patients were treated with guanabenz acetate to control blood pressure, followed by 17Beta-estradiol in the form of hydroalcoholic gel administered for 21 of 28 days of each cycle, for 3 cycles. Patients were evaluated before, during and 2 months after estrogen administation. Systolic and diastolic blood pressure or heart rat did not present any significant change in any patient when compared to those periods with the antihypertensive drug only (pretreatment period and 60 days after estrogen therapy was discontinued). Plasma biological markers of hepatic estrogenic action (plasma renin activity, antithrombin III, triglycerides, total cholesterol and lipoproteins) also remained unchanged during the study. Hormone treatment was effective, as indicated by the relief of menopausal symptoms, a decrease in FSH levels (73.48 + 27.21 to 35.09 + 20.44 IU/I, P<0.05), and an increase in estradiol levels (15.06 + 8.76 to 78.7 + 44.6 pg/ml, P<0.05). There was no effect on LH (18.0 + 9.5 to 14.05 + 8.28 IU/I). Hormone levels returned to previous values after estrogen treatment was discontinued. The data indicate that short-term percutaneous 17Beta-estradiol replacement therapy, at the dose used, seems to be a safe hormone therapy for hypertensive menopausal women. Nevertheless, a controlled, prospective, randomized clinical assay with a larger number of subjects is needed to definitely establish both the beneficial and harmful effects of hormone replacement therapy in hypertensive women.