Effects of norethisterone acetate addition to estradiol in long term HRT

Objective: The aim of this study was to evaluate the efficacy and tolerabil ity of hormone replacement therapy (HRT) among postmenopausal women living in the Lund area of Southern Sweden and to analyze treatment effects in dif ferent types or routes of HRT administration, as well as to compare with un opposed estrogen therapy. Method: in an ongoing, large population-based, pr ospective cohort study, this interim analysis included 3900 women. Of them, 693 postmenopausal women were eligible in the present analyses as they con tinued to use one of the four commercial HRT products for at least 2-3 year s, i.e. continuous oral estradiol (E-2) 2 mg + norethisterone acetate (NETA ) 1 mg (CON-O), sequential oral estradiol 2 mg + norethisterone acetate 1 m g (CYC-O), sequential transdermal estradiol 50 mu g + norethisterone acetat e 250 mu g (CYC-TRANS) and estradiol monotherapy. These women completed one generic questionnaire and one specific 'hormonal' questionnaire, as well a s a personal interview pertaining to sociodemographics, detailed status of HRT use, and therapeutic efficacy and untoward side-effects by HRT. Results : comparing the three combined E-2 + NETA groups with E-2 monotherapy, the beneficial effects on sexual desire and emotional well-being were significa ntly less in the combined groups than in E-2 monotherapy group. There was n o significant difference regarding the negative side-effects between the gr oups. No significant difference was found between CON-O and CYC-O groups ei ther in positive effects or in negative side-effects. A higher prevalence o f positive effects was found in CYC-TRANS group than that in CYC-O group, e specially in amelioration of sleep and urinary symptoms. Higher odd ratios of negative effects by HRT, such as irregular bleeds, weight gain, food cra ving and skin disorders were also found in CYC-TRANS group. Conclusion: in long-term HRT administration, the addition of a progestogen in HRT could co mpromize the beneficial effects of estradiol, particularly, the effects on women's emotional well being and psychosexual functioning. Administration o f NETA continuously and sequentially had similar therapeutic efficacy and t olerability. More marked positive effects, such as improving of sleep and u rinary symptoms, as well as nuisance side-effects, i.e. irregular bleeds, w eight gain, food craving and skin disorders were encountered by the women u sing sequential transdermal regimen (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.