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.

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.

Continuously combined hormone replacement therapy and bone turnover: the influence of dydrogesterone dose, smoking and initial degree of bone turnover.

In this study we examined whether the effect of continuously combined hormone replacement therapy (HRT) on bone metabolism is influenced by dydrogesterone dose, smoking and initial degree of bone turnover. In a double-blind randomized study, 123 healthy postmenopausal women (mean age 51.7 years; range 30-61 years) received 17 beta-estradiol, 2 mg orally per day, continuously combined with either 2.5, 5, 10 or 15 mg of dydrogesterone daily. At baseline and at 3 and 6 months of therapy, bone formation was assessed by determining total alkaline phosphatase (TAP), bone-derived alkaline phosphatase (BAP), and the carboxy-terminal propeptide of collagen type I (PICP) in serum; bone resorption was assessed by the calcium/creatinine (Ca/Creat) and hydroxyproline/creatinine (Hp/Creat) ratio in 2-h fasting urine, and the serum carboxy-terminal pyridinolyne cross-linked telopeptide of collagen type I (ICTP). Dydrogesterone dose did not influence the effect of HRT on any of the bone markers. Combining the data of the four treatment groups, the decrease in each marker, compared to baseline values, was significant. However, in non-smokers, compared to smokers, after 6 months of therapy the decline in BAP and TAP was significantly more pronounced and the plasma estradiol level was significantly higher. For each bonemarker at baseline, women in the highest quartile, compared to women in the lowest quartile, showed a significantly stronger decrease in this marker in response to HRT. We conclude that dydrogesterone dose does not modify the effectiveness of replacement therapy. However, smoking and a low bone turnover at baseline may diminish its beneficial effect on bone.

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.

Dose-response characteristics for arginine-stimulated insulin secretion in man and influence of hyperglycemia.

To test the hypothesis that glucose only affects the responsiveness (maximum velocity) of the beta-cell to arginine without changing the sensitivity (ED50) of the beta-cell to arginine, we investigated the influence of hyperglycemia on the responsiveness and sensitivity of arginine-induced insulin secretion in eight healthy male volunteers. Plasma C-peptide and insulin levels achieved during infusions of five doses of arginine (30 min) with and without a 60-min hyperglycemic clamp (17 mmol/L) were analyzed using a modified Michaelis-Menten equation. At euglycemia, the ED50 (half-maximally stimulating serum arginine concentration) was significantly less for first phase than for second phase plasma C-peptide secretion (0.7 +/- 0.1 vs. 2.7 +/- 0.4 mmol/L; P less than 0.002). Hyperglycemia significantly increased arginine-induced insulin secretion at all arginine infusion rates (P less than 0.01) without significantly altering the ED50 for either phase. We conclude 1) that the regulation of arginine-induced insulin secretion differs between both phases of insulin secretion, and 2) that a 1-h infusion with glucose significantly potentiates arginine-induced insulin secretion without influencing the difference in regulation of both phases of arginine-induced insulin secretion, supporting the validity of the use of arginine as a secretagogue in studies involving hyperglycemia.