A double‐blind, randomised trial comparing the effects of tibolone and continuous combined hormone replacement therapy in postmenopausal women with menopausal symptoms

Abstract

Objective To compare the effects of two postmenopausal regimens on menopausal symptoms, bleeding episodes, side effects and acceptability.Design Double-blind, randomised controlled trial.Setting Twenty-nine sites in Denmark, nine in Norway and six in Sweden.Participants Four hundred and thirty-seven postmenopausal women with menopausal complaints. None of these women had had a hysterectomy.Interventions Daily treatment with tibolone 2.5 mg (n = 218) or l7p-oestradiol 2 mg plus norethisterone acetate 1 mg (E,lNETA) (n = 219). Main outcome measures Hot flushes, sweating episodes, vaginal dryness, assessment of sexual life and bleeding patterns; at baseline and after 4, 12,24 and 48 weeks.Results Treatment with either preparation significantly reduced mean scores for hot flushes, sweating episodes and vaginal dryness. The overall discontinuation rate was 28% (tibolone 25%, E,/NETA 31%; P = 0.14), mostly during the first six months. There was a markedly lower cumulative incidence of bleeding or spotting episodes with tibolone compared with E,/NETA ( P < O.OOOl), mainly during the first six treatment cycles. Conclusions Both tibolone and E,/NETA effectively alleviate menopausal symptoms. However, tibolone caused significantly fewer bleeding or spotting episodes, which were reflected by lower overall rates of bleeding, as well as lower drop-out rates due to bleeding.

Pharmacologically Active Metabolites of Currently Marketed Drugs: Potential Resources for New Drug Discovery and Development

“…3a-and 3b-Hydroxytibolone are the main metabolites in the circulation with a half life of about 7 h, and are responsible for the eŠectiveness of tibolone in alleviating climacteric symptoms and prevention of bone loss. 110) Tibolone and 7a-methylnorethisterone have produced similar inhibition of aromatase activity, 58％ and 65％, respectively, to those obtained from MCF-7 cell study. 111) Venlafaxine Venlafaxine is a phenethylamine bicyclic anti-depressant.…”

Extracts from "Clinical Evidence": Menopausal symptoms

“…Urogenital system: We found two RCTs. The first RCT found no significant difference between tibolone and combined hormonal treatment in terms of subjective reports of vaginal lubrication; both interventions improved lubrication compared with baseline 28. The second RCT (437 women) found that tibolone improved sexual satisfaction compared with oestradiol plus norethisterone (P<0.05) 31.…”

“…Vasomotor symptoms: We found three RCTs, two of tibolone versus continuous combined oestrogen/progestogen treatment over 48 and 52 weeks (672 women with menopausal symptoms) 28 29 and one versus placebo over 16 weeks (82 women with menopausal symptoms) 30. The first RCT found a slightly greater reduction in hot flushes with the combined regimen than with tibolone over 48 weeks (P=0.01).…”

Tibolone in postmenopausal women: a review based on recent randomised controlled clinical trials

“…In addition, T is locally converted into the D 4isomer by 3b-OH steroid dehydrogenase isomerase, which prevents endometrial proliferation and hyperplasia; finally, it stimulates sulphotransferase enzymes and induces the inhibition of sulphatase, causing a further reduction in estrogenic activity in the endometrium [5,83]. The International Tibolone Consensus Group highlighted the good profile of tolerability which is associated with a better vaginal bleeding control as compared to EPT, especially in the first 6 months of therapy [1].…”