S.P.Suhonen. P.Lahteenmaki, I.Rauramo
Steroid Research Laboratory, Institute of Biomedicine, P.O. Box 8. 00014 University of Helsinki. Finland and Leiras Oy, P.O. Box 325. 00101 Helsinki, Finland.
ALM Kok, CW Burger, PHM van de Weiier. GA Voetberg, ERA Peters-Muller, P Kenemans
Project Ageing Women, Academic Hospital Free University, Amsterdam, The Netherlands.
MCP Rees. Brockie J, Suffling K, O'Byrne K, Harris A and Clarke PJ
John Radcliff Hospital, Oxford, OX3 9DU, UK.
Sustained-release of steroids is possible utilizing polydimethylsiloxane as the carrier material. Parenteral long-term estradiol (E2) therapy with subdermal polydimethylsiloxane implants was studied in 10 postmenopausal women (mean age 53 years and mean serum FSH 82 mIU/1 at baseline). Each woman received 2 implants, and the average in vitro release-rate of E2 was 20 μg/24 h per implant. Serum eoncentralions of estrone. E2 and FSH and alleviation of menopausal symptoms were followed for 12 months. Short-term pharmacocinetic evaluation of serum E2 concentrations was carried out during initial two weeks of treatment to evaluate the initial release of E2, The peak median serum E2 concentration was observed 8 hours after insertion (115 pg/ml; range 03-161 pg/ml). After the first 2 weeks the median E2 concentration was 42 pg/ml declining slowly thereafter. Even though median E2 concentration at 12-month control was significantly lower (28 pg/ml) than 2 weeks after insertion, suppression of FSH was maintained during the 12-month observation time successfully as well as the control of menopausal symptoms. Subdermal implants offer an acceptable long-term parenteral sustained-release E2 delivery to avoid supraphysiological E2 concentrations. Adequacy of the long-term serum F/2 concentrations to prevent osteoporosis and cardiovascular disease remains to be determined.
The effect of the dydrogesterone dose in continuously combined hrt regimens on micturition complaints
The prevalence rate of urogenital complaints (genital atrophy, incontinence and recurrent urinary tract infection) are high in postmenopausal women. Purpose of the study was to establish the effectiveness of continuously combined HRT (ccHRT) regimens of 2mg estradiol with different dydrogesterone dosages (2.5; 5; 10 and 15mg) for the relief of micturation complaints in post-menopausal women.
102 women were entered in a double blind, randomized, six months trial. Assessments (standardized questionnaire and test for bacteriuria) were done at baseline and at the end. 95 women completed the 6 month study period. At baseline urinary incontinence was reported by 44.1%; diurnal frequency (more than 6 voids per day) and nocturia (more than 2 voids per night) by 28.4% of the women. At the end of the trial 23.3% of the women reported to be cured of their urinary incontinence. The number of voids in the group with diurnal frequency decreased significantly (P=0.01); the same effect was found in the group with nocturia ( < 0.001) of which 65.4% of the women reported that the nocturia had disappeared. Bacteriuria was present in the 7 women before and after treatment. Different doses of dydrogesterone did not effect the findings. Postmenopausal women report improvement on urinary incontinence and nocturia after 6 months of a ccHRT regimens irrespective of the dydrogesterone dose used.
Megestrol acetate to treat vasomotor symptoms
The safety of oestrogen hormone replacement therapy in women with previous breast cancer is controversial. Progestagens are used to treat breast cancer and have been reported to be effective for vasomotor symptoms. We therefore undertook a study to examine the effect of megestrol acetate 40mg to control hot flushes in women with previous breast cancer.
Twenty three women from the Oxford Menopause Oncology Clinic were recruited. After 2 weeks baseline on no treatment, women took megestrol acetate 40mg daily for 2 months.
Flushes/ day were recorded with a daily diary. The Greene Menopausal Symptom Score was administered at baseline and after 2 months' treatment. Flushes were significantly reduced within one month [ < 0.01] and this was maintained at 2 months [baseline median 7. range 1-21; month 1 median 2, range 0-13; month 2 median 0, range 0-11]. Similar improvement was seen in menopausal symptom scores. Megestrol acetate provides a useful option for the treatment of menopausal vasomotor symptoms for women with previous breast cancer.