Estrogen replacement therapy continuously combined with four different dosages of dydrogesterone: effect on calcium and lipid metabolism.

Lipid and bone metabolism was studied in 165 healthy postmenopausal women treated with 2 mg 17 beta-estradiol continuously combined with one of four doses (2.5, 5, 10, or 15 mg) of dydrogesterone in a double blind randomized study design. Fasting blood and urine samples were drawn at baseline and after 3 and 6 months of treatment. Bone remodeling was significantly reduced in all four treatment groups, as indicated by the decrease in serum corrected calcium, phosphate, and alkaline phosphatase and the urinary calcium/creatinine ratio. A dose response of dydrogesterone on these indices was not found. With all four dosages of dydrogesterone, lipid profile (total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, and apolipoproteins) improved significantly; however, this was less pronounced with the highest dydrogesterone dose. Our data suggest that continuously applied dydrogesterone in combined hormone replacement therapy does not annihilate the beneficial effects on bone remodeling and lipid metabolism induced by estrogens.

Oral 17 beta-estradiol continuously combined with dydrogesterone lowers serum lipoprotein(a) concentrations in healthy postmenopausal women.

Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerosis. Serum Lp(a) concentrations increase after menopause, and postmenopausal estrogen replacement appears to decrease Lp(a) levels. In a randomized, double blind study, we examined the effects of 6-month treatment with daily 17 beta-estradiol (E2; 2 mg, orally) continuously combined with one of four dosages [2.5 mg (n = 41), 5 mg (n = 38), 10 mg (n = 38), and 15 mg (n = 20)] of dydrogesterone on fasting serum Lp(a) concentrations in 137 healthy postmenopausal women. At baseline, no significant differences were noted among the four treatment groups. During the study period of 6 months the median serum Lp(a) concentration decreased significantly from 128 mg/L (range, 5-1660) to 110 mg/L (range, 1-1530) in the total population, corresponding to a reduction of 13% (P < 0.001). The percent changes in serum Lp(a) correlated positively with the percent changes in serum E2 at 3 as well as 6 months of therapy (r = 0.38; P < 0.001 and r = 0.35; P < 0.001, respectively). A dose response of dydrogesterone on serum Lp(a) was not found. In addition, serum lipids and (apo)lipoproteins improved significantly in all four treatment groups. In conclusion, oral E2 continuously combined with dydrogesterone has beneficial effects on the lipid and lipoprotein profile and is effective in lowering Lp(a) concentrations in postmenopausal women.

A randomized controlled study of the effects of 17beta-estradiol-dydrogesterone on plasma homocysteine in postmenopausal women.

OBJECTIVE: To investigate the effects of oral 17beta-estradiol (E2) -dydrogesterone on fasting plasma homocysteine concentrations in healthy postmenopausal women. METHODS: We studied 27 postmenopausal women who were assigned randomly to either a treatment group (n = 14) or a control group (n = 13). During the first 12 months of the study, treatment consisted of oral E2, 1 mg daily, combined sequentially with dydrogesterone 5 or 10 mg (14 days per 28-day treatment cycle). Thereafter, women were treated with oral E2, 2 mg daily, combined sequentially with dydrogesterone, 10 mg daily (14 days per 28-day treatment cycle) for a period of 3 months. The control group received no treatment. Fasting plasma total homocysteine concentrations were determined at baseline and 3, 12, and 15 months after study entry. RESULTS: At baseline, plasma homocysteine levels did not differ between the groups. After 15 months of hormone treatment mean plasma homocysteine concentration was lowered by 12.6% compared with baseline (P < .001; analysis of variance for repeated measures). Plasma homocysteine levels were not altered in the control group. The interaction between treatment and time for homocysteine levels was significantly different between the groups (P < .001; analysis of variance for repeated measures). The decrease in plasma homocysteine levels correlated inversely with the increase in serum E2 levels after 3 and 12 months of hormone treatment (r = -.54, P < .05 and r = -.56, P < .05, respectively). CONCLUSION: Plasma fasting homocysteine concentrations are lowered by E2-dydrogesterone therapy in postmenopausal women.

Postmenopausal oral 17beta-estradiol continuously combined with dydrogesterone reduces fasting serum homocysteine levels.

OBJECTIVE: To investigate the effects of oral 17beta-estradiol administration continuously combined with dydrogesterone on fasting serum total homocysteine levels in postmenopausal women. DESIGN: Randomized, double-blind study. SETTING: Gynecologic outpatient department of a university hospital. PATIENT(S): One hundred thirty-five healthy, nonhysterectomized postmenopausal women. INTERVENTION(S): Oral micronized 17beta-estradiol (2 mg/d) continuously combined with one of four dosages of dydrogesterone (2.5 mg [n = 41], 5 mg [n = 38], 10 mg [n = 37], or 15 mg [n = 19]) was given for 6 months. MAIN OUTCOME MEASURE(S): Fasting serum total homocysteine concentrations. RESULT(S): The mean fasting serum total homocysteine concentrations in the overall study population decreased significantly (by 13.5%) after the first 3 months of treatment and remained unchanged thereafter. No influence of dydrogesterone dosage was found. The greatest reduction in total homocysteine concentration was obtained in women with the highest baseline levels. CONCLUSION(S): Continuously combined hormone replacement therapy lowers fasting serum total homocysteine levels significantly in postmenopausal women. This decrease may be one of the mechanisms that underlie the cardioprotective effects of postmenopausal hormone replacement therapy.

Micturition complaints in postmenopausal women treated with continuously combined hormone replacement therapy: a prospective study.

OBJECTIVES: To study parameters of the micturition pattern in postmenopausal women and the effect of an oral continuously combined HRT-regimen. METHODS: Hormone therapy consisted of 2 mg 17 beta-oestradiol in combination with either 2.5, 5, 10 or 15 mg dydrogesterone, orally once a day. The baseline assessment was done just before starting hormone replacement therapy, the second assessment took place after 6 months of hormone therapy. Data were collected using a standardized questionnaire and focused on diurnal urinary frequency, nocturnal urinary frequency and urinary incontinence as parameters of the micturition pattern. Furthermore, bacteriuria was assessed. RESULTS: One hundred and two women entered the study and 95 women completed 6 months of hormone replacement therapy. Urinary incontinence was reported by 44.1% of the women, in 19.6% of the women it occurred more than twice a week. Both diurnal frequency and nocturnal frequency was reported by 28.4% of the women. For women with frequency or nocturia, the number of voids significantly decreased after 6 months hormone replacement therapy. Nocturia disappeared in 65.4% of the women after treatment and 23.3% reported to be cured of their urinary incontinence. Bacteriuria was present in the same seven women before and after hormone treatment. Dydrogesterone dose did not influence treatment outcomes. CONCLUSIONS: Postmenopausal women report improvement on urinary incontinence and nocturia after 6 months of a continuously combined hormone replacement therapy regimen. The improvement was most outspoken with regard to nocturia. Bacteriuria was not influenced. Different doses of dydrogesterone did not effect these findings.

Sequentially combined hormone replacement therapy reduces impedance to flow within the uterine and central retinal arteries in healthy postmenopausal women.

OBJECTIVE: The purpose of this study was to investigate the long-term effects of combined hormone replacement therapy on the impedances of the uterine, central retinal, and ophthalmic arteries in healthy postmenopausal women. STUDY DESIGN: In a prospective controlled study we randomly assigned 30 healthy postmenopausal women (mean age, 52 +/- 3 years) to 2 groups. Women in the hormone replacement therapy group (n = 15) received 1 mg micronized 17beta-estradiol daily sequentially combined with 5 or 10 mg dydrogesterone for 14 days of each 28-day cycle during 12 months and 2 mg 17beta-estradiol combined with 10 mg dydrogesterone thereafter for a period of 3 months. The control group (n = 15) received no treatment. Color Doppler ultrasonography was used to measure the impedance to flow (pulsatility index) within the uterine, central retinal, and ophthalmic arteries in the 17beta-estradiol phase at baseline and after 3, 12, and 15 months. RESULTS: With respect to values in the control group, 12 months of hormone replacement therapy was associated with a significantly lower (by 39%) mean pulsatility index of the uterine artery (decrease from baseline of 25% in hormone replacement therapy group and increase of 14% in control group) and a significantly lower (by 29%) mean pulsatility index of the central retinal artery (decrease of 9% in hormone replacement therapy group and increase of 20% in control group). After 3 months this effect was already evident. During hormone replacement therapy the reductions in mean pulsatility index values of the uterine and central retinal arteries with respect to baseline were larger (both P =.002) in the women with high pretreatment pulsatility index values than in those with low pretreatment values. The baseline pulsatility index of the uterine artery correlated positively with age and with duration of amenorrhea (r = 0.42, P =. 01; r = 0.48, P =.008; respectively). CONCLUSION: These results suggest that 12 months of sequentially combined hormone replacement therapy with a low dose of estradiol (1 mg) lowers arterial impedance in specific vascular territories. These data may help in understanding the effects of hormone replacement therapy on the cerebral circulation.

Short-term hormone replacement therapy: reduced plasma levels of soluble adhesion molecules.

BACKGROUND: Epidemiological data have suggested that the use of hormone replacement therapy (HRT) is associated with a decreased risk of cardiovascular disease. Vascular endothelium and adhesion molecules play an important role in the initiation and progression of atherosclerosis. MATERIAL AND METHODS: Prospective, randomized, placebo-controlled 12-week study. Sixty healthy, normotensive postmenopausal women received either micronised oestradiol 2 mg alone (n = 16, E2 group), or sequentially combined with a progestagen; E2 + P groups trimegestone 0.5 mg (E2 + T, n = 14) or dydrogesterone 10 mg (E2 + D group, n = 14) or placebo (n = 16). Data were collected at baseline and at 4 and 12 weeks. RESULTS: Twelve weeks of treatment with E2 or E2 + P was associated with a significant decrease in the plasma concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), vascular cell adhesion molecule-1 (sVCAM-1), and thrombomodulin (sTM). The average decrease in these markers was about 9%. In women treated with trimegestone the decreases were larger than in those treated with dydrogesterone; for sICAM-1 (-15% vs. -2%; P < 0.0001), sVCAM-1 (-15% vs. +3%; P = 0. 003) and sTM (-9% vs. -4%; P = 0.11). Plasma levels of endothelin-1 (ET-1) decreased (by 13%) only in women treated with E2 + P. In the E2 group, flow-mediated, endothelium-dependent vasodilatation increased by 6 percentage points after 12 weeks (P = 0.07 vs. baseline, P = 0.02 vs. E2 + P, and P = 0.17 vs. placebo). CONCLUSION: Short-term treatment with E2 or E2 + trimegestone reduces plasma levels of sICAM-1, sVCAM-1 and sTM. ET-1 decreased only in the E2 + P groups. Different types of progestagens may differentially affect sICAM-1, sVCAM-1 and sTM levels, which may be relevant for the choice of type HRT.