estradiol-drospirenone-combination and drospirenone

Unlike other currently available progestogens, drospirenone (DRSP) has a pharmacological profile, which closely mimics that of endogenous progesterone, most notably potent anti-aldosterone and anti-androgenic effects. Consequently, DRSP, when combined with 17beta-estradiol (E2) as hormone replacement therapy (HRT), offsets E2-related water and sodium retention by blocking the mineralocorticoid receptor. This review evaluates the potential benefits offered by DRSP as the progestin component of HRT with respect to its anti-aldosterone activity, which translates into positive effects on body weight and blood pressure in clinical trials of continuous, combined E2/DRSP in post-menopausal women. In a 1-year, large-scale, randomised, controlled trial, E2 1 mg/DRSP 2 mg significantly decreased mean body weight by 1.2 kg versus baseline (P<0.001), whereas patients receiving E2 1 mg gained weight. E2 1 mg/DRSP 2 mg also significantly lowered mean systolic blood pressure (SBP) by 9.0 mmHg from baseline (P<0.05) versus 3.7 mmHg in the E2 1 mg group (P=0.220) in a sub-group of hypertensive women. In addition, E2/DRSP was not associated with hyperkalaemia (potassium > or =5.5 meq/L) irrespective of concomitant use of ACE inhibitors, angiotensin II receptor antagonists or non-steroidal anti-inflammatory drugs, and co-morbid diabetes mellitus. In summary, as well as effectively treating climacteric symptoms, DRSP 2 mg combined with E2 1 mg has shown positive effects on body weight and blood pressure in clinical trials, most likely due to DRSP's anti-aldosterone properties. This combination may therefore offer an alternative therapeutic option with additional benefits beyond current HRT agents for symptomatic post-menopausal women.

Topics: Androstenes; Blood Pressure; Body Weight; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Female; Humans; Menopause; Mineralocorticoid Receptor Antagonists; Progesterone Congeners; Randomized Controlled Trials as Topic; Renin-Angiotensin System

Progesterone has a high affinity for the mineralocorticoid receptor and is an antagonist of aldosterone. Almost all synthetic progestogens are devoid of an antimineralocorticoid effect, and are unable to antagonize the salt-retaining effect of estrogens. This property could be one cause of the weight gain and increase in blood pressure associated with the use of combined oral contraceptives and, in some susceptible women, with postmenopausal hormone replacement therapy (HRT). This review illustrates the results of clinical studies with drospirenone, a new progestogen with antialdosterone activity. In normally menstruating women, 3 mg drospirenone per day, taken from day 5 to day 25 of the cycle, inhibits ovulation. A combination of 3 mg drospirenone with 30 microg ethinylestradiol (Yasmin, Schering AG, Berlin, Germany) is a highly effective and well-tolerated oral contraceptive, with an overall Pearl Index of 0.57 and an adjusted Pearl Index of 0.09. In addition, this combination leads to mild natriuresis and a slight compensatory activation of the renin-aldosterone system. This effect hasbeen clinically demonstrated: compared with an oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel, 30 microg ethinylestradiol/3 mg drospirenone, given over 6 months, led to slight decreases in body weight and blood pressure. For postmenopausal HRT, 2 mg drospirenone was combined with 1 mg 17beta-estradiol (Angeliq, Schering AG, Berlin, Germany) for continuous treatment. To evaluate the endometrial safety of this combination, data were assessed from 520 postmenopausal women receiving 1 mg 17beta-estradiol and drospirenone (1, 2 or 3 mg per day) for at least 100 weeks. There were no cases of hyperplasia or carcinoma during the entire study period, and 85-92% of women had an atrophic/inactive endometrium. Data from two studies, with a treatment duration of at least 6 months, demonstrated a decrease in mean systolic blood pressure of 1.8 mmHg and a decrease in mean diastolic blood pressure of 3.8 mmHg, after treatment with 1 mg 17beta-estradiol/2 mg drospirenonefor 28 weeks. However, in a subgroup of slightly hypertensive women (initial blood pressure of more than 140/90 mmHg), the mean decrease in systolic blood pressure after 28 weeks of treatment with 1 mg 17beta-estradiol/2 mg drospirenone was 12.5 mmHg, and the mean decrease in diastolic blood pressure was 9.4 mmHg. Since high blood pressure is a cardiovascular risk factor, the use of

Topics: Androstenes; Contraceptives, Oral; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Estrogens; Female; Humans; Hypertension; Mineralocorticoid Receptor Antagonists; Progesterone Congeners; Renin-Angiotensin System

Drospirenone is a novel progestogen that possesses antimineralocorticoid activity. This activity is seen clinically in its effects on physiological parameters, body weight, general well-being and fluid-related symptoms. Clinical studies with an oral contraceptive containing 30 microg ethinylestradiol and 3 mg drospirenone (Yasmin, Schering AG, Berlin, Germany) and a new continuous combined oral hormone replacement therapy (HRT) containing 1 mg 17beta-estradiol and 2 mg drospirenone (Angeliq, Schering AG) were all designed specifically to evaluate treatment effects on body weight and cardiovascular function, both of which can be influenced by aldosterone receptor antagonism. Weight gain during traditional oral contraceptive and HRT use has been one of the main reasons for poor compliance and discontinuation. Women receiving hormone therapy with 1 mg 17beta-estradiol/2 mg drospirenone had either no weight change or a small decrease, while those receiving estradiol alone tended to increase in weight. Mean body weight after 1 year of treatment with 1 mg 17beta-estradiol/2 mg drospirenone decreased by 1.2 kg (p < 0.001). Studies using different drospirenone doses in combination with estradiol indicate that the effect on body weight is dependent on the dose of drospirenone, and that this is due to drospirenone's antimineralocorticoid activity. These data are in agreement with previous studies that compared the changes in body weight in young women receiving for 13 or 26 cycles the oral contraceptives 30 microg ethinylestradiol/3 mg drospirenone or 30 microg ethinylestradiol/150 microg desogestrel (Marvelon, Organon International); 30 microg ethinylestradiol/3 mg drospirenone had a more favorable effect on body weight, with the mean body weight remaining lower than baseline for the majority of women. A variety of physical and emotional changes have been linked to hormonal fluctuations during the menstrual cycle. Fluid retention-related symptoms, such as breast tenderness, swelling, abdominal bloating and skin changes, may affect well-being and quality of life. Improvements in these cycle-dependent disorders, together with some psychological symptoms, such as fatigue and depressive mood, are well documented with the use of 30 microg ethinylestradiol/3 mg drospirenone. Therefore, the effects of hormone therapy with 1 mg 17beta-estradiol/2 mg drospirenone on quality of life were assessed in the Women's Health Questionnaire. Significant improvements were observed in

Topics: Androstenes; Body Weight; Contraceptives, Oral; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Female; Humans; Mineralocorticoid Receptor Antagonists; Patient Compliance; Premenstrual Syndrome; Progesterone Congeners; Quality of Life

Following American randomised controlled epidemiologic studies (HERS, WHI), regulatory authorities have advised that postmenopausal hormone therapy, using minimal effective dosages, is indicated for the first line treatment of climacteric symptoms during a limited, and problem-related period of time, and for second line prevention of osteoporosis when a non-hormonal treatment cannot be used. Observation of a discrete increase in cardiovascular and breast cancer risk in hormone users currently appears to partly justify this rather strict attitude. We report here results of studies concerning a new continuous combination regimen (Angeliq), associating a "half-dose" estrogen (estradiol 1 mg/d) with potentially less thrombogenic impact than a standard (2 mg) dose, and the new progestin drospirenone (2 mg/d). The latter demonstrates a high level of endometrial safety as well as unique antialdosterone properties (reduction of symptoms related to water retention; potential cardioprotective effects) and consistent antiandrogenic properties, useful for both metabolic and clinical issues. Accordingly, Angeliq constitutes a new therapeutic approach, in good agreement with updated guidelines related to hormone replacement therapy.

Topics: Androstenes; Dose-Response Relationship, Drug; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Female; Humans; Menopause; Mineralocorticoid Receptor Antagonists

Drospirenone is a novel progestogen that, combined with 17β-estradiol, reduces the frequency and severity of menopausal vasomotor symptoms (VMS) in different populations. This double-blind, multicenter study compared the efficacy, safety and tolerability of 2 mg drospirenone/1 mg estradiol (DRSP/E2) vs. placebo in Chinese postmenopausal women with moderate to severe VMS.. Women, aged 45-65 years, were randomized to DRSP/E2 (n=183) or placebo (n=61) once daily for four 28-day cycles. Changes in the frequency and severity of hot flushes were analyzed as primary variables, together with other climacteric and urogenital symptoms, clinical global improvement, adverse events and physical/gynecological parameters.. Relative changes in numbers of hot flushes/week were -80.4% for DRSP/E2 vs. -51.9% for placebo (treatment difference -28.5%, p<0.0001). There were trends toward a greater reduction in severity of hot flushes with DRSP/E2 treatment. Patients treated with DRSP/E2 were more often free from sweating episodes (p<0.0001) and vaginal dryness (p=0.0008). Other climacteric symptoms, including nervousness and pollakisuria, followed a trend of greater response with DRSP/E2. Similar to other combination HRT regimens, DRSP/E2 increased occurrences of bleeding, but these decreased over time. Adverse events in patients treated with DRSP/E2 were mostly mild to moderate and withdrawal rates were low.. Daily treatment of postmenopausal Chinese women with DRSP/E2 for 16 weeks significantly reduced the incidence of hot flushes and demonstrated advantages vs. placebo for other climacteric symptoms. These results indicate that DRSP/E2 is effective, safe and well tolerated in postmenopausal Chinese women.

Topics: Aged; Androstenes; China; Double-Blind Method; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Female; Hot Flashes; Humans; Middle Aged; Mineralocorticoid Receptor Antagonists; Placebos; Postmenopause; Vaginal Diseases

To compare the clinical and metabolic effects of drospirenone-estradiol (Angeliq) versus tibolone (Livial) in postmenopausal women.. Twenty-seven postmenopausal women of group 1 took Angeliq (1 dose every two days) while another group 2 (n = 26) received tibolone (2.5 mg every two days) as hormone replacement therapy for 12 weeks. A retrospective analysis was used to evaluate the clinical efficacy, safety and risk factors of cardiovascular metabolism. The clinical data were collected before and after treatment, including personal interview, medical examination and ultrasound imaging of pelvic, breast and carotid artery.. No statistically significant inter-group differences existed in age or body mass index. Before treatment, the level of E2 was (12 ± 10) ng/L, triglyceride (TG) (2.0 ± 1.1) mmol/L, lipoprotein-a (LPa) (47 ± 43) mmol/L in group 1 versus (23 ± 12) ng/L, (1.3 ± 0.7) mmol/L and (28 ± 14) mmol/L in group 2. After 12-week treatment, (30 ± 18) ng/L, (1.6 ± 1.1) mmol/L and (37 ± 36) mmol/L in group 1 versus (23 ± 9) ng/L, (1.1 ± 0.6) mmol/L and (18 ± 12) mmol/L in group 2. A greater incidence of vaginal bleeding and thicker endometrium were found in group 1.. Angeliq can relieve menopausal symptoms. And its functions of regulating lipid metabolism and protecting cardiovascular system are better than those of Livial. However, its wider acceptability is limited by vaginal bleeding, thicker endometrium and breast pain.

Topics: Androstenes; Drug Combinations; Estradiol; Estrogen Receptor Modulators; Female; Humans; Norpregnenes; Postmenopause; Retrospective Studies; Uterine Hemorrhage

Drospirenone--a new 17 alpha-spironolactone derivate is a progestin with aldosterone receptor antagonism activity (PARA) thanks to which it decreases sodium and fluid retention.. The aim of our study was to estimate the electrolytes level and renal function parameters in blood during the therapy of low dose oral contraceptive containing drospirenone.. The group consisted of 22 young women in mean age 25,9 +/- 4,3 years, without contraindications to hormonal contraception used specimen containing 20 microg ethinyloestradiol and 3.0 mg drospirenone during 12 cycles. Blood levels of electrolytes (sodium, potassium, calcium, phosphorus and chloride) and renal function parameters (creatinine, urea and uric acid) were evaluated before and after 3, 6 and 12 cycles of the treatment. There were no statistically significant differences observed in serum concentration of electrolytes and renal function parameters.. The therapy of a low dose oral contraceptive containing 20 microg ethinyloestradiol and 3.0 mg drospirenone does not influence the electrolyte equilibrium and renal function.

Topics: Adult; Age Factors; Androstenes; Contraceptives, Oral; Drug Administration Schedule; Drug Combinations; Estradiol; Female; Humans; Kidney; Patient Compliance; Poland; Progesterone Congeners; Water-Electrolyte Balance; Young Adult