[show abstract][hide abstract] ABSTRACT: A prospective, randomized, open-label study was conducted to evaluate effects on mammographic density in postmenopausal and late perimenopausal women receiving continuous combined or sequential combined hormone replacement therapy (HRT).
The subjects were randomized to treatment with low-dose continuous combined HRT containing 1 mg 17beta-estradiol plus 0.5 mg norethisterone acetate (Activelle) or a sequential combined HRT regimen consisting of 0.625 mg conjugated equine estrogens for 28 days plus 5 mg medrogestone for 14 days (Presomen). Mammograms were obtained at baseline and after 9 cycles (each 28 days) of treatment.
The majority of women (approximately two-thirds in each treatment group) had no changes in mammographic breast density between baseline and the final study visit. There were no marked differences between treatment groups. Approximately 20% of women in both groups had a slight increase in mammographic density. Only 10-14% of women in both groups had a pronounced increase in mammographic density. The analyses of the degree of change showed no remarkable differences between treatments.
These results indicate that the increase in mammographic density with a low-dose continuous combined HRT regimen is no greater than that with a sequential combined HRT regimen. The type of progestogen does not have an impact on the extent of mammographic density changes.
[show abstract][hide abstract] ABSTRACT: The aim of this study was to compare the incidence of women presenting irregular bleeding episodes following 9 months of treatment with a low dose continuous combined hormone replacement therapy consisting of estradiol (E(2)) and norethisterone acetate (NETA) versus a sequential hormone replacement therapy consisting of conjugated equine estrogens (CEE) and medrogestone (MG). Secondary aims were to establish the relationship between menopausal age and the occurrence of irregular bleeding for both therapies and to assess the efficacy of both therapies in alleviating menopausal symptoms.
This was a stratified and randomised, open label study conducted with late peri and postmenopausal women at 35 sites in Austria and Germany. A total of 446 women were randomly allocated into two cohorts based on time since last bleeding and then stratified to either a low dose continuous combined therapy consisting of 1 mg E(2) and 0.5 mg NETA for 28 days or a sequential therapy consisting of 0.625 mg CEE for 28 days and 5 mg MG for the final 14 days. Bleeding and menopausal complaints were continuously assessed. Treatments were administered for 9 lunar months.
The incidence rate of women presenting irregular bleeding episodes including spotting during cycle 9 was 12.2% with 1mgE(2)/0.5mgNETA and 25.8% with 0.625mgCEE/5mgMG (P = 0.0014). In the group of postmenopausal women (time since last bleeding > or = 12 months) the incidence of irregular bleeding during cycle 9 was 11.0% for 1mgE(2)/0.5mgNETA and 25.0% for 0.625mgCEE/5mgMG). In the group of late perimenopausal women (time since last bleeding 6-11 months) the incidence of irregular bleeding was similar for both treatments at cycle 3, but markedly less in patients with 1mgE(2)/0.5mgNETA at cycle 6 and 9, being significantly different compared to patients with 0.625mgCEE/5mgMG at cycle 6 (P < 0.05). The cumulative rate of amenorrhea (no bleeding or spotting) achieved with 1mgE(2)/0.5mgNETA was 89% for the postmenopausal women and 83.7% for the late perimenopausal women. Both treatments relieved menopausal complaints equally effective.
Regarding the occurrence of irregular bleeding, the low dose continuous combined therapy was superior to the sequential therapy (0.625mgCEE/5mgMG). The low dose continuous combined E(2)/NETA regimen is also suitable for late perimenopausal women since more than 80% of the women had no bleeding or spotting after 9 months of treatment.
[show abstract][hide abstract] ABSTRACT: To investigate the efficacy and tolerability of a new 7-day transdermal sequential estradiol/levonorgestrel patch (Fem7 Combi; Merck KGaA; Germany), versus placebo, as hormone replacement therapy in menopausal women.
A multicentre, randomized, clinical study consisting of a 3-week screening phase, a 12-week double-blind, placebo-controlled treatment phase, and a 12-week open, follow-up phase. Women aged 40-65 years with an intact uterus and menopausal complaints were randomized to either 2 weeks of an estradiol mono patch (50 microg per 24 h) followed by 2 weeks of an estradiol/levonorgestrel combination patch (50 microg/10 microg per 24 h), or a placebo patch, for three 28-day cycles. Changes in the Kupperman Index and the frequency of hot flushes were assessed.
The sequential use of a 7-day estradiol patch and a 7-day estradiol/levonorgestrel patch was superior to placebo in reducing menopausal symptoms, and was well tolerated. At the end of the treatment phase, there was a statistically significant reduction in the Kupperman Index score versus placebo (P<0.0001), and a statistically significant difference between groups in the proportion of patients with a reduction in the number of hot flushes (at least 50% versus baseline). During the open follow-up phase, there was a marked reduction in the Kupperman Index score and the number of hot flushes for patients switched from placebo to active study medication. The active medication was effective throughout the 1-week application period.
The new 7-day transdermal sequential estradiol/levonorgestrel patch was well tolerated, providing rapid and effective relief of menopausal symptoms. The addition of low-dose levonorgestrel did not influence the beneficial effects of estradiol.