Effects of tibolone and continuous combined hormone replacement therapy on bleeding rates, quality of life and tolerability in postmenopausal women

Abstract

Objective To compare the effects of tibolone and conjugated equine oestrogens continuously combined with medroxyprogesterone acetate on bleeding rates, quality of life (QoL) and tolerability. Design A double-blind, randomised comparative trial.Setting Thirty-seven centres in six European countries.Population Five hundred and one postmenopausal women, under 65 years of age with an intact uterus.Interventions For 12 months, women received daily treatment with tibolone 2.5 mg (n ¼ 250), or conjugated equine oestrogens 0.625 mg continuously combined with medroxyprogesterone acetate 5 mg (CEE-MPA, n ¼ 251). Main outcome measures The primary outcome was vaginal bleeding rate during cycles 4 -6. The secondary outcomes were vaginal bleeding rate during cycles 1 -3, 7-9 and 10 -13, cumulative bleeding rate, QoL, wellbeing, climacteric symptoms, urogenital complaints and tolerability. Results Treatment with tibolone led to a significantly lower bleeding rate during cycles 4 -6 compared with CEE -MPA (15.0% vs 26.9%; P ¼ 0.004); there was a similar difference during cycles 1-3. Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital complaints. By intent-to-treat analysis, tibolone significantly improved sexual drive, interest and/or performance, compared with CEE -MPA at 12 months ( P ¼ 0.017). Although both treatments were well tolerated, there was a significantly lower incidence of breast tenderness with tibolone than CEE -MPA (2.4% vs 17.1%; P < 0.001). Conclusion The vaginal bleeding rate during cycles 4-6 was significantly lower in women using tibolone.Both treatments improved QoL, wellbeing, climacteric symptoms and urogenital symptoms. Breast tenderness was significantly less frequent with tibolone.

Tibolone and low‐dose continuous combined hormone treatment: vaginal bleeding pattern, efficacy and tolerability

“…Tibolone's advantageous profile on the breast with respect to breast pain/tenderness is known from previous comparative studies with higher dose estrogen plus progestogen. 8,11 Which treatment to choose for an individual woman is ultimately a decision of the woman and her counselling doctor. Tibolone is known for its added benefits on sexual wellbeing, including an improvement in urogenital and vaginal complaints, as well as motivational aspects of sexuality.…”

“…7 As a result, tibolone is clinically associated with a high amenorrhoea rate and relatively few irregular bleedings. 8,9 Estrogenic effects on the breast are low due to inhibition of the local enzyme systems, which impair the local formation of active estrogens. 10 Clinically, this results in few breast complaints in women using tibolone and no or limited increase in breast density.…”

“…10 Clinically, this results in few breast complaints in women using tibolone and no or limited increase in breast density. 8,11 Continuous combined estrogen plus progestogen preparations also offer efficacious treatment without regular monthly bleeding. However, relatively high rates of irregular bleeding, especially during the first 3 months of treatment, have been reported with continuous combined 17b estradiol (2 mg) plus norethisterone acetate (1 mg) (E 2 /NETA, Kliogest Ò ; Nova Nordisk, Copenhagen, Denmark), as well as with other continuous combined HT regimens.…”

“…However, relatively high rates of irregular bleeding, especially during the first 3 months of treatment, have been reported with continuous combined 17b estradiol (2 mg) plus norethisterone acetate (1 mg) (E 2 /NETA, Kliogest Ò ; Nova Nordisk, Copenhagen, Denmark), as well as with other continuous combined HT regimens. 8,9 The occurrence of vaginal bleeding during treatment, especially in the first 3 months, leads to poor adherence and causes early discontinuation. 9,[12][13][14] In addition, adverse effects related to treatment such as breast pain and tenderness cause some women to discontinue treatment, may induce fear and anxiety and additional medical examinations.…”

“…[16][17][18][19] Higher dose estrogen-progestogen combinations compare unfavourably with tibolone with respect to bleeding and breast-related adverse events (AEs), whereas lower dose regimens have not been compared with tibolone. 8,9,[20][21][22] Therefore, the aim of the present study was to compare the occurrence of vaginal bleeding, efficacy and tolerability of 2.5 mg tibolone with 1 mg E 2 and 0.5 mg NETA.…”