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P305 Treatment with testosteronundecanoate in postmenopausal women — A pharmacological study
P303
P304 USE OF A LEVONORGESTREL RELEASING INTRAUTERINE DEVICE IN SUBSTITUTIVE ESTROGENIC THERAPY IN MENOPAUSE.
TRANSDERMAL ESTRADIOL REPLACEMENT USING CHLOR-MADINONE ACETATE AS SEQUENTIAL PROGESTOGEN
A Becorui, F Toni, P Bordonaro, M Barzagli, C Tantini, S Ottanelli,
A 0 blue&, F Melcherf, F-U Deuringer’, T. Roemer’, H. Seege#,T H Lipped,
Department of obstetric and Gynecology, Florence, Italy.
University Hospitals, Dept. OB/GYN, Greifswald, Germany
GB Massi, University
of
’ Tuebingen,
* Mannheim,
3
We must adequately balance estrogenic treatment in subjects in natural menopause with progesterone or progestinics for at least 12 days a month in order to contrast the proliferative effects of estrogen on the endometrium. With associative cyclical estro-progestinic treatment there is often flow due to suspension similar in quantity and length to that of the fertile age. Many patients show scarse compliance, especially since HRT is protracted for years. Thus, to avoid a cyclical flow in subjects undergoing sub-stitutive estrogenotherapy we applied an IUD releasing 20mcg of LEVONORGESTREL every day for 5 years. We studied 19 postmenopausal patients, all of whom had undergone endometrial biopsy. There was 1 case of proliferative, 13 cases of atrophic, and 5 cases of secretive endometrium. Treatment began with the application of the IUD and was administered for 3 weeks per month. 3 months after insertion a transvaginal echography and a histeroscopy were performed, showing an atrophic endometrium in every case. After the 1 st month 14 patients had absence of flow, and only 1 had a modest flow 3 months after application of the IUD.
Chlormadinone acetate (CMA) has been widely used as progestational component in oral contraceptives mainly due to its antiandrogenic properties. For use in hormonal replacement only very few studies have been published. We treated 224 peri-and postmenopausal women with (a) cyclic estradiol (E2) (3 weeks on, 1 week off) combined with oral sequential CMA (12 days, beginning in the 2nd week of each cycle) or with (b) continuous E2 combined with oral CMA (12 days, beginning on the 1. day in each calendar month). Dosage E2 0.05 mg/die, dosage CIVIA 2 mg/die. Results: I.) Bleeding pattern during 4 months (n=224) showed longer withdrawal bleedings with continuous compared to cyclic E2 (5.4 f 2.1 / 4.4 f 1.5 days, p
P305
P306
TREATMENT WITH POSTMENOPAUSAL
TESTOSTERONUNDECANOATE WOMEN - A PHARMACOLOGICAL STUDY
IN
MANAGEMENT
OF THE MENOPAUSE CONTINUOUS HRT
WITH
PG Sknorile. R AnselmiAngeli, S Ronca,F Bechini. G Plotti,
A Fliiter, J Nathorst-Bdiis,K Carlstriim,B vonSchoultz, Dept of Obstetrics and Gynecology, Karolinska Hospital, S-171 76 Stockholm, Sweden and Huddinge University Hospital, Huddinge, Sweden The purpose of this study was to investigate if stable serum concentrations and adequate levels of testosterone were achieved with 10 mg testosteronundecanoate orally. This dose was given to ten postmenopausal women each morning for one week. Before starting medication two blood samples were taken with 2 hours interval measuring the basal hormonal values. The first day after medication blood samples were taken between 8 am and 4 pm with two hours interval. Following days one test was taken every morning. Pretreatment hormonal values were in the normal range. Serum concentrations of testosterone (T), dihydro-testosterone (DHT), androstenedione (A-4) and sex-hormone binding globuhne (SHBG) were analysed. Treatment with testosteronundecanoate significantly increased T, DHT and A-4 levels, but SHBG levels remained unchanged. A fast absorption was found with highest concentrations of T and DHT after 2 hours and for A-4 after six hours. Steady-state levels (median and range) for T were 3.1 (0.510.5) nmol/l, for DHT 3.1 (0.6-7.7) nmol/l and for A-4 4.9 (2.412.5) nmol/l. The pharmacokinetic findings of this study concluded a rapid absorption of testosteronundecanoate. The steady-state levels were sufficient with 40 mg of testosteronundecanoate but large individual variations were found.
211
S.Filippo Neri Hospital, Department of Obstetrics-Gynecology Martinotti, 20 Rome Italy
Via
800 patients (spontaneous menopause), selected from 2800 women have been studied. All patients have been treated with continuous combined HRT Medroxyprogesteroneacetate Smg/day; percutaneous 178estradio1, 25ug/day (Oestrogel@IscovescoParis) transdermalestradiol, 25ug/day (Epiestrol@Roerig); oralconjugated equineestrogenso, 625mg/day ([email protected]). We analysed 24months HRT (19200cycles). The admission criteria included: body weight, blood pressure <140/90mmHg, no diabetes, osteoporosis with Nordin test >1.7(speedy loss) computed bone densitometry with bone mass - bone density decreased at least of 30%. Ultrasonography with normal endometrial pattern, low dose mammography, Papanicolau test excluded pelvic or breast disease/cancer. Moreover, we performed HDL, LDL, androstenedione. Our data show a fast decrease of androstenedione and consequently a reduction of estrone, created by aromatase. Serum lipids have a relative reduction of total cholesterol an LDL and increase of HDL with a lower risk of cardiovascular disease. This improvement is faster with oral therapy but not statistically significant. The continuous HRT does not stimulate the endometrium, the lack of menstruation means absence of stimulation; bleeding episodes are an important sign of possible endometrial pathology and become a sign for a larger diagnostic search, whilst the lack of bleeding is a sign of therapeutic safety. We performed only HRT plus calcium diet not lower than 1000 mg/day.
P304 USE OF A LEVONORGESTREL RELEASING INTRAUTERINE DEVICE IN SUBSTITUTIVE ESTROGENIC THERAPY IN MENOPAUSE.
TRANSDERMAL ESTRADIOL REPLACEMENT USING CHLOR-MADINONE ACETATE AS SEQUENTIAL PROGESTOGEN
A Becorui, F Toni, P Bordonaro, M Barzagli, C Tantini, S Ottanelli,
A 0 blue&, F Melcherf, F-U Deuringer’, T. Roemer’, H. Seege#,T H Lipped,
Department of obstetric and Gynecology, Florence, Italy.
University Hospitals, Dept. OB/GYN, Greifswald, Germany
GB Massi, University
of
’ Tuebingen,
* Mannheim,
3
We must adequately balance estrogenic treatment in subjects in natural menopause with progesterone or progestinics for at least 12 days a month in order to contrast the proliferative effects of estrogen on the endometrium. With associative cyclical estro-progestinic treatment there is often flow due to suspension similar in quantity and length to that of the fertile age. Many patients show scarse compliance, especially since HRT is protracted for years. Thus, to avoid a cyclical flow in subjects undergoing sub-stitutive estrogenotherapy we applied an IUD releasing 20mcg of LEVONORGESTREL every day for 5 years. We studied 19 postmenopausal patients, all of whom had undergone endometrial biopsy. There was 1 case of proliferative, 13 cases of atrophic, and 5 cases of secretive endometrium. Treatment began with the application of the IUD and was administered for 3 weeks per month. 3 months after insertion a transvaginal echography and a histeroscopy were performed, showing an atrophic endometrium in every case. After the 1 st month 14 patients had absence of flow, and only 1 had a modest flow 3 months after application of the IUD.
Chlormadinone acetate (CMA) has been widely used as progestational component in oral contraceptives mainly due to its antiandrogenic properties. For use in hormonal replacement only very few studies have been published. We treated 224 peri-and postmenopausal women with (a) cyclic estradiol (E2) (3 weeks on, 1 week off) combined with oral sequential CMA (12 days, beginning in the 2nd week of each cycle) or with (b) continuous E2 combined with oral CMA (12 days, beginning on the 1. day in each calendar month). Dosage E2 0.05 mg/die, dosage CIVIA 2 mg/die. Results: I.) Bleeding pattern during 4 months (n=224) showed longer withdrawal bleedings with continuous compared to cyclic E2 (5.4 f 2.1 / 4.4 f 1.5 days, p
P305
P306
TREATMENT WITH POSTMENOPAUSAL
TESTOSTERONUNDECANOATE WOMEN - A PHARMACOLOGICAL STUDY
IN
MANAGEMENT
OF THE MENOPAUSE CONTINUOUS HRT
WITH
PG Sknorile. R AnselmiAngeli, S Ronca,F Bechini. G Plotti,
A Fliiter, J Nathorst-Bdiis,K Carlstriim,B vonSchoultz, Dept of Obstetrics and Gynecology, Karolinska Hospital, S-171 76 Stockholm, Sweden and Huddinge University Hospital, Huddinge, Sweden The purpose of this study was to investigate if stable serum concentrations and adequate levels of testosterone were achieved with 10 mg testosteronundecanoate orally. This dose was given to ten postmenopausal women each morning for one week. Before starting medication two blood samples were taken with 2 hours interval measuring the basal hormonal values. The first day after medication blood samples were taken between 8 am and 4 pm with two hours interval. Following days one test was taken every morning. Pretreatment hormonal values were in the normal range. Serum concentrations of testosterone (T), dihydro-testosterone (DHT), androstenedione (A-4) and sex-hormone binding globuhne (SHBG) were analysed. Treatment with testosteronundecanoate significantly increased T, DHT and A-4 levels, but SHBG levels remained unchanged. A fast absorption was found with highest concentrations of T and DHT after 2 hours and for A-4 after six hours. Steady-state levels (median and range) for T were 3.1 (0.510.5) nmol/l, for DHT 3.1 (0.6-7.7) nmol/l and for A-4 4.9 (2.412.5) nmol/l. The pharmacokinetic findings of this study concluded a rapid absorption of testosteronundecanoate. The steady-state levels were sufficient with 40 mg of testosteronundecanoate but large individual variations were found.
211
S.Filippo Neri Hospital, Department of Obstetrics-Gynecology Martinotti, 20 Rome Italy
Via
800 patients (spontaneous menopause), selected from 2800 women have been studied. All patients have been treated with continuous combined HRT Medroxyprogesteroneacetate Smg/day; percutaneous 178estradio1, 25ug/day (Oestrogel@IscovescoParis) transdermalestradiol, 25ug/day (Epiestrol@Roerig); oralconjugated equineestrogenso, 625mg/day ([email protected]). We analysed 24months HRT (19200cycles). The admission criteria included: body weight, blood pressure <140/90mmHg, no diabetes, osteoporosis with Nordin test >1.7(speedy loss) computed bone densitometry with bone mass - bone density decreased at least of 30%. Ultrasonography with normal endometrial pattern, low dose mammography, Papanicolau test excluded pelvic or breast disease/cancer. Moreover, we performed HDL, LDL, androstenedione. Our data show a fast decrease of androstenedione and consequently a reduction of estrone, created by aromatase. Serum lipids have a relative reduction of total cholesterol an LDL and increase of HDL with a lower risk of cardiovascular disease. This improvement is faster with oral therapy but not statistically significant. The continuous HRT does not stimulate the endometrium, the lack of menstruation means absence of stimulation; bleeding episodes are an important sign of possible endometrial pathology and become a sign for a larger diagnostic search, whilst the lack of bleeding is a sign of therapeutic safety. We performed only HRT plus calcium diet not lower than 1000 mg/day.