Benefits and risks of long-term low-dose oral continuous combined hormone therapy

• Published in: Maturitas 2007-03, Vol.56 (3), p.231-248
• Main Authors: van de Weijer, P.H.M, Mattsson, Lars-Åke, Ylikorkala, Olavi
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; bone-mineral density; Breast Neoplasms - etiology; Cardiovascular Diseases - etiology; conjugated equine estrogens; continuous combined hrt; Continuous combined oestrogen–progestagen combinations; coronary-heart-disease; Dose-Response Relationship, Drug; Drug Therapy, Combination; early postmenopausal women; Estrogen Replacement Therapy - adverse effects; Estrogen Replacement Therapy - methods; Estrogens - adverse effects; Estrogens - therapeutic use; Female; Geriatrics; Geriatrik; Gynecology. Andrology. Obstetrics; Hormone therapy; Humans; Internal Medicine; Long-term administration started in early postmenopausal women; Long-term effect on bone; Long-term endometrial safety; Low-dose; Medical sciences; medroxyprogesterone acetate; Menopause - drug effects; Middle Aged; norethindrone acetate; norethisterone acetate; Obstetrics and Gynecology; Obstetrics, Gynecology and Reproductive Medicine; Osteoporosis, Postmenopausal - prevention & control; Pharmacokinetics of estrogens; Pharmacokinetics of progestagens; Progesterone - adverse effects; Progesterone - therapeutic use; Puberal and climacteric disorders (male and female); randomized controlled-trial; replacement therapy; Reproduktionsmedicin och gynekologi; Risk Factors
• ISSN: 0378-5122; 1873-4111
• DOI: 10.1016/j.maturitas.2006.08.004

Abstract Objectives Current recommendations for hormone therapy (HT) are mainly based on findings from studies using standard dose regimens in older women who had a different health profile from those who start HT soon after the onset of menopause. Methods We, therefore, reviewed controlled trials assessing the efficacy, safety and tolerability of low-dose oral continuous combined HT (cc-HT) started for treatment of climacteric symptoms. This review is limited to oral cc-HT regimens over sequential regimens as most postmenopausal women prefer not to have a return of uterine bleeding, and to studies of at least 2 years in duration. Results Low-dose cc-HT is effective in alleviating climacteric symptoms and in maintaining bone density over prolonged periods, although no data were available regarding fracture risk. No increased risk of coronary heart disease, venous thrombo-embolism or stroke during the use of low-dose cc-HT was reported in the long-term studies and no definitive evidence for an increased risk of breast cancer was found. Breakthrough bleeding during the first months of use is less common than with standard dose HT and amenorrhoea is achieved in most women over time. These regimens are safe for the endometrium and are well tolerated, with a low incidence of adverse events compared with standard doses. Conclusions Current evidence from controlled trials indicates that low-dose oral cc-HT appears effective and safe. This makes it a good choice for the alleviation of climacteric symptoms, and for this purpose long-term administration of low-dose cc-HT does not seem to impose serious health risks. However, more long-term study data and direct head-to-head comparisons between various low-dose preparations are needed to support or rectify the safety aspects.