Low-dose Oral Hormone Therapy Research Articles

A randomized study of low-dose conjugated estrogens on sexual function and quality of life in postmenopausal women

To evaluate the effects of combined vaginal and oral low-dose estrogen plus progestogen therapy (EPT) on the frequency and severity of dyspareunia, sexual function, and quality of life in recently postmenopausal women. This outpatient, double-blind, randomized, placebo-controlled trial enrolled 285 healthy, sexually active postmenopausal women aged 45 to 65 years. Women received either one daily oral low-dose conjugated estrogens (0.45 mg)/medroxyprogesterone (1.5 mg) tablet for six 28-day cycles along with 1 g conjugated estrogens vaginal cream (0.625 mg), intravaginally for the first 6 weeks of the trial or a placebo cream and placebo tablet. Efficacy was evaluated using the McCoy Female Sexuality Questionnaire, self-reported daily diary cards, the Brief Index of Sexual Functioning-Women (BISF-W), and the Women's Health Questionnaire. The EPT group had a significant decrease in the frequency of dyspareunia compared with baseline and placebo in an analysis of responses to the McCoy Female Sexuality Questionnaire. Also, EPT was associated with a significant improvement in a woman's level of sexual interest, frequency of orgasm, and pleasure of orgasm. There was no effect of EPT use on coital frequency. The EPT group had significant improvement in receptivity/initiation and relationship satisfaction, although not in other BISF-W domains, versus placebo (BISF-W analysis) and significant improvement versus placebo on most Women's Health Questionnaire responses. EPT provided a statistically significant improvement compared with placebo in dyspareunia, sexual experience, and quality of life as measured in this study. In general, EPT also improved self-reported sexual perception and enjoyment significantly compared with placebo.

P57 Differential impact of conventional and low dose oral hormone therapy (HT), tibolone and raloxifene on sex hormone binding globulin (SHBG)

P57 Differential impact of conventional and low dose oral hormone therapy (HT), tibolone and raloxifene on sex hormone binding globulin (SHBG)

30 Differential effects of conventional and low dose oral hormone therapy (HT), tibolone and raloxifene on functionality of the activated protein C system

30 Differential effects of conventional and low dose oral hormone therapy (HT), tibolone and raloxifene on functionality of the activated protein C system

27 Differential effects of conventional and low dose oral hormone therapy (HT), tibolone, and raloxifene on coagulation and fibrinolysis

27 Differential effects of conventional and low dose oral hormone therapy (HT), tibolone, and raloxifene on coagulation and fibrinolysis

Differential impact of conventional and low-dose oral hormone therapy (HT), tibolone and raloxifene on functionality of the activated protein C system

Recent studies have shown that hormone therapy (HT) is associated with an acquired resistance to activated protein C (APC). The aims of the present study were to evaluate a possible dose-response relationship and differential effects of different HT regimens on functionality of the APC system. Two hundred two healthy women were randomly assigned to receive treatment for 12 weeks with tablets containing either low-dose HT containing 1 mg 17ss-oestradiol + 0.5 mg norethisterone acetate (NETA) (n = 50), conventional-dose HT containing 2 mg 17ss-oestradiol and 1 mg NETA (n = 50), 2.5 mg tibolone (n = 51), or 60 mg raloxifene (n = 51). Normalized APC system sensitivity ratios (nAPCsr) were determined in plasma collected at baseline and after 12 weeks using a thrombin generation-based APC resistance test probed with either recombinant APC (rAPC) or thrombomodulin (rTM). NAPCsr increased in both the conventional- and low-dose HT groups, consistent with reduced sensitivity to APC. The increase was slightly more pronounced in the conventional-dose group, but the difference between the two HT groups was not statistically significant. The sensitivity to APC was only marginally altered in those allocated to tibolone. Consequently, tibolone showed a different phenotype as compared with the low-dose HT group. A small increase in nAPCsr with both rAPC and rTM was seen in the raloxifene-group, but the increase was less than in the low-dose HT group. Our findings indicate that oestrogen-progestin therapy induces an APC resistant phenotype, which may be related to dose, whereas tibolone and raloxifene only marginally alter the sensitivity to APC.

Differential effects of conventional and low dose oral hormone therapy (HT), tibolone, and raloxifene on coagulation and fibrinolysis

Introduction We have recently reported that different hormone regimens given to healthy post-menopausal women had markedly different effects on activation of coagulation. Low-dose hormone therapy (HT) and raloxifene, as opposed to conventional-dose HT and tibolone, were associated with no or minor activation of coagulation. The aim of this study was to elucidate the mechanism(s) for differences in coagulation activation by analysing clotting and fibrinolytic factors and coagulation inhibitors. Materials and methods 202 healthy women were randomly assigned to receive treatment for 12 weeks with either low dose HT containing 1 mg 17 β-estradiol + 0.5 mg norethisterone acetate (NETA) ( n = 50), conventional dose HT containing 2 mg 17 β-estradiol and 1 mg NETA ( n = 50), 2.5 mg tibolone ( n = 51), or 60 mg raloxifene ( n = 51) in an open-label design. Results The conventional-and low-dose HT groups generally showed similar effects, i.e., reductions in both clotting factors and inhibitors, but the effects were markedly more pronounced in the conventional-dose HT group. Compared with the low-dose HT group those treated with tibolone showed more pronounced decreases in factor VII, less reduction of antithrombin and protein C and even increased levels in protein S and tissue factor pathway inhibitor. As opposed to the low-dose HT group the reductions in inhibitors in the raloxifene group were smaller. Moreover in those allocated to raloxifene reduced levels of fibrinogen were seen. Conclusions Our study demonstrates that the different HT regimens and raloxifene exert differential effects on coagulation factors, inhibitors and fibrinolytic factors.