Bleeding pattern and climacteric symptoms during different sequential combined HRT regimens in current use.

Four sequential combined oestrogen and progestogen regimens were compared in terms of bleeding pattern and relief of climacteric symptoms. Treatment was with either 2 mg 17 beta-oestradiol with 1 mg norethisterone acetate [E2 + NETA]; 2 mg oestradiol valerate with 75 micrograms levonorgestrel [E2V + LNG]; 2 mg oestradiol valerate with 10 mg medroxyprogesterone acetate [E2V + MPA]; or 1.5 mg 17 beta-oestradiol with 150 micrograms desogestrel [E2 + DG]. A placebo-controlled study lasting 12-24 months was completed by 143 healthy early postmenopausal women. Bleeding lengths were not substantially different; in all regimens the majority of women were bleeding for 3-6 days. Bleeding onset showed differences when related to the 11th day of progestogen addition; in the regimen with E2V + LNG, 21% of the women women were bleeding before the 11th day of progestogen addition 26% on, and 53% after that day. In the regimen with E2V + MPA, 56% of the women were bleeding before the 11th day, 28% on, and 17% after that day, whereas in the regimen with E2 + DG, 15% of the women were bleeding before the 11th day, 5% on, and 80% after that day. All regimens reduced climacteric symptoms to the same extent. Breast tenderness occurred in all the regimens, except in the E2 + DG. Conclusively, the differences between the responses to treatment were not conspicuous. However, our data indicate that one regimen (E2 + DG) resulted in optimal bleeding control, optimal effect on climacteric symptoms, and no production of breast tenderness.

[Oral contraceptives: knowledge and compliance]. / P-piller: viden og komplians.

One hundred and twenty (120) women, taking contraceptive pills, underwent a structured interview with a view elucidating their knowledge of the physiology of menstruation, the action and side effects of contraceptive pills and their compliance in the taking of contraceptive pills. The most important sources of information were the medical letters in magazines and the women's own doctors, while the teaching in the Folkeskole (primary and lower secondary school) had not had any major influence on the level of information. Well over one third of the interviewed women knew the most important action mechanism of the contraceptive pill, and half of the women could give a satisfactory explanation of the physiology of menstruation. Twenty-four percent (24%) thought that pregnancy could not occur until 1-2 months after the woman had ceased taking the pill. There was high compliance among the women i.e. that their behavior was correct when they had forgotten to take one or two contraceptive pills, when bleeding was irregular, and when beginning on a new package of pills. Eighty-three percent (83%) had experienced side effects that could be related to contraceptive pills. The investigation shows that there is a need for more efficient information about the effects of the Pill and about the physiology of menstruation.

PIP: 120 women using oral contraceptives (OC) participated in a structured interview with a view to establish their knowledge of the physiology of menstruation, the action and side effects of contraceptive pills, and their compliance in taking OCs. The most important sources of information were the medical columns in magazines and the women's own doctors, while only a small number received their information from the instruction in the Folkeskole (primary and lower secondary school). 39% of the interviewed women knew the most important action mechanism of the contraceptive pill, i.e., the suppression of release of eggs. 43% of the women could give a satisfactory explanation of the hormonal physiology of menstruation. 24% thought that pregnancy could not occur until 1-2 months after the woman had ceased taking the pill, and 64% stated that one can get pregnant right after halting OC use. There was a significant negative correlation between social status and the scoring of information (r = 0.24, p 0.01) and a significant positive correlation between age and information scoring (r = 0.38, p 0.001). Information level was higher among women in steady relationships than among women without steady partners (r = 0.27, p 0.01), and it increased with the number of pregnancies (r = 0, 18, p 0.05). There was a positive significant correlation between the duration of pill taking and the information score (r = 0.31, p 0.001). The median score was 18.0. There was high compliance among the women, i.e., their behavior was correct when they had forgotten to take one or two contraceptive pills, when bleeding was irregular, and when starting on a new package of pills. 48% had forgotten to take their pills at some time. 83% had experienced side effects that could be related to contraceptive pills. 30% had minor menstrual pain, and in 22% the amount of bleeding diminished. The investigation shows that there is a need for efficient information about the effects of the pill and about the physiology of menstruation.

Changes in calcanean bone mineral occurring spontaneously and during hormone replacement therapy in early post-menopausal women.

The spontaneous calcanean bone loss occurring in healthy early post-menopausal women and the effect of two hormone replacement therapies (HRT's) were investigated in a longitudinal study. There was no difference between the right and left calcanean BMC or BMD (p > 0.15). The spontaneous bone loss was similar at all the skeletal sites measured, with a mean spontaneous loss in calcanean BMD of 1.6% over one year. Both HRT's significantly (p < 0.01) prevented the bone loss from all skeletal sites irrespective of the weight-bearing or content of trabecular bone, and (for the weight-bearing bones) there was even a gain in calcanean BMC and BMD and spinal BMD (p < 0.01). Bone mineral of the calcaneus and the spine correlated equally to body weight (r approximately 0.4, p < 0.001), whereas bone mineral in the forearm was not correlated to body weight. The correlations between the changes in bone mineral at the sites measured were all significant (r approximately 0.2-0.4).

Two new combinations of estrogen and progestogen for prevention of postmenopausal bone loss: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Bone mass, calcium and lipid metabolism, climacteric symptoms, bleeding, blood pressure, and weight changes were studied in 62 healthy postmenopausal women at 3-month intervals throughout 2 years of treatment with continuous estradiol valerate (2 mg) plus cyproterone acetate (1 mg), sequential estradiol valerate (2 mg) plus levonorgestrel (75 micrograms), or placebo. During the 2 years of the study, bone mineral content of the distal and ultradistal regions of the forearm (measured by single-photon absorptiometry) remained unchanged in the hormone groups, whereas bone mineral content at these sites decreased by 5 and 6%, respectively, in the placebo group. Bone mineral density in the spine (measured by dual-photon absorptiometry and dual-energy x-ray absorptiometry) increased by 3-4% in the hormone groups and decreased by 2% in the placebo group. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium/creatinine) decreased significantly to premenopausal levels in the hormone groups, but remained unchanged in the placebo group. Serum concentrations of total and low-density lipoprotein cholesterol were significantly reduced by 5-10% (P less than .05-.01) in the estradiol + cyproterone acetate group and by 10-15% (P less than .001) in the estradiol valerate + levonorgestrel group. There were no significant changes in high-density lipoprotein cholesterol in the hormone groups. Virtually no changes were observed in the placebo group. Climacteric symptoms and hot flushes were significantly reduced in both hormone groups compared with the placebo group.(ABSTRACT TRUNCATED AT 250 WORDS)

Measurements of bone mineral density of the proximal femur by two commercially available dual energy X-ray absorptiometric systems.

Two dual energy X-ray absorptiometric (DXA) instruments have recently become commercially available for local bone densitometry: the QDR-1000 (Hologic Inc.) and the DPX (Lunar Radiation Corp.). We report the precision, influence of femoral rotation, correlation and agreement of bone mineral measurements of the proximal femur by these two instruments. In vitro (femur phantom) short-term precision was 1.1%-3.5%, and the long-term precision was 1.2%-3.8%. In vivo (groups of 10 premenopausal and 10 post-menopausal women) short-term precision of duplicate measurements was 1.6%-4.7%, and long-term precision was 1.9%-5.5%. Overall, the precision for Ward's triangle was over 3% and that for the femoral neck and trochanter, 2%-3%. Rotation of a femur phantom produced a statistically significant change in the bone mineral density (BMD) of the femoral neck. Within a clinically relevant range of femoral rotation (20 degrees inward rotation +/- 5 degrees) the coefficient of variation (CV%) increased by a mean factor of 1.1-1.4. Although the correlation (r less than 0.9) between BMD measurements of the proximal femur by the DPX and QDR-1000 in 30 postmenopausal women was high, there was lack of agreement between the two instruments. We found no statistically significant differences between the right and left femur in 30 postmenopausal women. A bilateral femur scan took a mean total time of about 22 min. We conclude that with the introduction of DXA instruments, the precision of bone mineral measurements of the proximal femur has improved. However, for comparability between commercially available DXA instruments, it might be advantageous if units were standardized.

Postmenopausal hormone replacement therapy prevents central distribution of body fat after menopause.

The reduction in cardiovascular risk induced by hormone replacement therapy is only partly explained by changes in serum lipids and lipoproteins. As body composition and body fat distribution in particular are independent predictors of cardiovascular disease, we investigated the effect of postmenopausal hormone therapy on body composition parameters directly measured. Sixty-two early postmenopausal women were followed up for 2 years in a prospective, randomized, placebo-controlled study. We found that combined estrogen-progestogen therapy prevented the increase in abdominal fat after menopause (P less than .05), and that this effect was independent of the effect on serum lipids and lipoproteins. The therapy reduced postmenopausal bone loss significantly (P less than .001), whereas it did not have a statistically significant influence on total body fat mass or total lean body mass. The findings of the present study suggest that some of the protective impact of postmenopausal hormone therapy on cardiovascular disease may be explained by the effect on body composition, in particular abdominal fat.

Desogestrel in hormone replacement therapy: long-term effects on bone, calcium and lipid metabolism, climacteric symptoms, and bleeding.

Seventy-three healthy, postmenopausal women, aged 45-54 years, were randomly assigned to one of three groups for 2 years of treatment: 17 beta-oestradiol 1.5 mg on days 1-12 and 17 beta-oestradiol 1.5 mg + desogestrel 150 micrograms on days 13-24 (E2/DG) or oestradiol valerate 2 mg on days 1-11 and oestradiol valerate 2 mg + medroxyprogesterone acetate 10 mg on days 12-21 (E2V/MPA) or placebo. Fifty-seven women (78%) completed the study. Bone mineral content of the distal regions of the forearms (measured by single photon absorptiometry, SPA) and bone mineral density of the spine (measured by dual energy X-ray absorptiometry, DXA) showed increases of 0.5-1% and 4-5%, respectively, in the hormone groups over 2 years. The placebo group exhibited a decrease in spinal bone density of 2% per year, and in the forearm of 2.5-3.5% per year. Biochemical estimates of bone turnover (serum alkaline phosphatase and fasting urinary calcium) decreased significantly to premenopausal levels in the hormone groups but remained unchanged in the placebo group. In both hormone groups total cholesterol decreased by about 9% (P less than 0.001), whereas low density lipoprotein cholesterol decreased by 16% in the E2/DG group and 20% in the E2V/MPA group (P less than 0.001). High density lipoprotein cholesterol showed only minor, insignificant changes in the hormone groups. The placebo group had virtually unchanged values. Climacteric symptoms, including hot flushes, were significantly reduced in both hormone groups. Bleeding occurred regularly in about 80% of the women.(ABSTRACT TRUNCATED AT 250 WORDS)

Bleeding patterns during continuous combined estrogen-progestogen therapy.

Bleeding and climacteric symptoms were recorded in two groups of postmenopausal women receiving either continuous combined estradiol and norethisterone acetate or estradiol and cyproterone acetate. Out of a sample of 99 postmenopausal women aged 45 to 54 years, 86 completed a 2-year, double-blind, placebo-controlled study. Comparison of the bleeding patterns in the two groups revealed a statistically significant difference: More women in the estradiol-cyproterone acetate group experienced bleeding and for a longer duration. Thirteen women in the estradiol-norethisterone acetate group were amenorrheic, compared with two in the other group. The Kupperman index score in both groups declined to about 30% to 40% of initial values (p less than 0.001). The hot flushes in both treatment groups decreased to a highly significant degree (p less than 0.001), to a value below 20% of baseline values. We conclude that a continuous combination of estrogen and progestogen can produce amenorrhea and symptomatic relief. However, the progestogen components seem to differ in their ability to control bleeding.

Progestogens: therapeutic and adverse effects in early post-menopausal women.

Progestogen treatment is associated with a number of subjective symptoms. In the present study, 148 healthy post-menopausal women suffering from mild climacteric symptoms were randomly allocated to 12 weeks of treatment with (a) 2 mg oestradiol valerate combined with cyproterone acetate, medroxyprogesterone acetate or levonorgestrel; (b) 1.5 mg 17 beta-oestradiol combined with desogestrel; or (c) placebo. Climacteric symptoms, Kupperman index scores and potential adverse progestogen effects were recorded before treatment and three times per month during therapy. All the hormone regimens had a rapid effect, reducing the severity of climacteric symptoms to about 30% of the baseline values (P less than 0.001) within one month. Hot flushes were reduced in severity and/or frequency by 76 100% within 3 months (P less than 0.001). The regimens which included hydroxyprogesterone derivatives produced a transient increase in breast tenderness. Other recorded potential adverse progestogen effects showed no significant changes during the study. We concluded that the addition of progestogens (whether 19-nortestosterone or hydroxyprogesterone derivatives) does not produce significant side effects during combined hormone replacement therapy.

Dual-energy x-ray absorptiometry: a precise method of measuring bone mineral density in the lumbar spine.

We compared two methods of measuring spinal bone mineral content and density (BMC/BMD): conventional dual-photon absorptiometry (DPA) and a more recent method, dual-energy x-ray absorptiometry (DEXA). The clinical usefulness of both methods was compared in the measurement of BMC in the forearm. DEXA had a long-term in vivo precision of 1% which was significantly better than that of DPA. Changes in the distribution of fatty tissue influenced the accuracy of the two spinal methods in different ways. Forearm BMC discriminated between the bone mass of early and late postmenopausal women to the same degree as DPA and DEXA. The variability in the response to estrogen treatment and placebo was much lower with DEXA and forearm BMC than with DPA. We conclude that DEXA provides a fast and precise measurement of spinal BMC/BMD. The accuracy remains to be evaluated for in vivo studies.