estradiol-drospirenone-combination and Body-Weight

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

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

This study aimed to explore the effects of continuous-combined estradiol 1 mg/drospirenone 2 mg (E2D) on cognitive performance in healthy, recently postmenopausal women.. A 6-month randomized, double-blind, placebo-controlled study was carried out in a university research center. Participants were 23 healthy postmenopausal women aged 49 to 55 years. Cognitive performance was assessed with a computerized cognitive battery administered to all participants on 0, 12, and 26 weeks. Functional magnetic resonance imaging was performed on 13 participants before and after treatment using tasks of verbal fluency and mental rotation.. E2D was not associated with an overall effect on cognitive performance. Functional magnetic resonance imaging results showed no difference between the groups for verbal fluency or mental rotation task performance at baseline. The mental rotation task was associated with increased blood oxygen level-dependent signalling in the placebo group in both occipital lobes and in the left superior parietal lobe after 26 weeks (P < 0.05), with no changes over time seen in the treatment group. The total menopausal symptom and sexual function domain scores improved after treatment in women randomized to E2D compared with the placebo group (both P < 0.05). Similarly, systolic blood pressure, weight, and body mass index were significantly lower in women randomized to E2D at 26 weeks (P < 0.05).. E2D has no detrimental effect on cognitive performance in early postmenopausal women. E2D significantly improves menopausal symptoms, sexual function, systolic blood pressure, and weight.

Topics: Androstenes; Blood Pressure; Body Mass Index; Body Weight; Cognition; Double-Blind Method; Drug Combinations; Estradiol; Estrogen Replacement Therapy; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Placebos; Postmenopause; Uterine Hemorrhage