Hormone Replacement Therapy (HRT)

Hormone replacement therapy (HRT) may consist of oestrogens alone or in combination with progestin. HRT slows bone turnover and increases bone mineral density (BMD) at all skeletal sites in early and late postmenopausal women [1, 2].

The anti-fracture efficacy of HRT has been assessed in observational studies, case-control studies, meta-analyses and randomized clinical trials: (Women’s Health Initiative), Heart and Estrogen/progestin Replacement Study (HERS), Women’s Interventional Study of long Duration Oestrogen after Menopause (WISDOM).

Overall, these analyses (except HERS) show that HRT decreases fragility fracture risk by 20-35% [3-5]. Discontinuation of HRT results in acceleration of bone turnover, decrease in BMD and eventual loss of anti-fracture efficacy.

However, despite this anti-fracture efficacy and a decrease in the risk for colon cancer, overall health risks generally outweigh benefits from HRT in older postmenopausal women with a higher incidence of cardiovascular events (unstable angina, thromboembolic stroke, venous thromboembolism including pulmonary embolism) and increased incidence of the endometrial and breast cancer [3-6].

HRT can also induce vaginal bleeding and breast tenderness. Finally, HRT may increase the risk of myocardial infarction, ovarian cancer as well as deterioration of the global cognitive function; however, the evidence is weaker.

More recent studies show that even low doses of HRT may protect bone by decreasing bone turnover markers (BTM) levels and preventing bone loss [7, 8]. The anti-fracture efficacy of these regimens has not been studied.

Currently, HRT is regarded as the acceptable treatment for osteoporosis only after all other treatments have been considered and when all the risks and benefits are carefully explained to the patient.

Women who decide to take HRT to relieve menopausal symptoms should use the lowest effective dose and for the shortest possible time [6].

Read IOF views re Global Consensus Statement on Menopausal Hormone Therapy issued in 2013


1. Bjarnason NH, Hassager C, Christiansen C 1998 Postmenopausal bone remodelling and hormone replacement. Climacteric 1:72-79
2. Torgerson DJ, Bell-Syer SE 2001 Hormone replacement therapy and prevention of nonvertebral fractures: a meta-analysis of randomized trials. JAMA 285:2891-2897
3. Cauley JA, Robbins J, Chen Z, Cummings SR, Jackson RD, LaCroix AZ, LeBoff M, Lewis CE, McGowan J, Neuner J, Pettinger M, Stefanick ML, Wactawski-Wende J, Watts NB 2003 Effects of estrogen plus progestin on risk of fracture and bone mineral density: the Women's Health Initiative randomized trial. JAMA 290:1729-1738
4. Vickers MR, MacLennan AH, Lawton B, Ford D, Martin J, Meredith SK, DeStavola BL, Rose S, Dowell A, Wilkes HC, Darbyshire JH, Meade TW 2007 Main morbidities recorded in the women's international study of long duration oestrogen after menopause (WISDOM): a randomised controlled trial of hormone replacement therapy in postmenopausal women. BMJ 335:239-250.
5. Hulley S, Furberg C, Barrett-Connor E, Cauley J, Grady D, Haskell W, Knopp R, Lowery M, Satterfield S, Schrott H, Vittinghoff E, Hunninghake D 2002 Noncardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/progestin Replacement Study follow-up (HERS II). JAMA 288:58-66
6. U.S. Preventive Services Task Force 2005 Hormone therapy for the prevention of chronic conditions in postmenopausal women: recommendations from the U.S. Preventive Services Task Force. Ann Intern Med 142:855-860
7. Gambacciani M, Cappagli B, Ciaponi M, Pepe A, Vacca F, Genazzani AR 2008 Ultra low-dose hormone replacement therapy and bone protection in postmenopausal women. Maturitas 59:2-6
8. Lindsay R, Gallagher JC, Kleerekoper M, Pickar JH 2005 Bone response to treatment with lower doses of conjugated estrogens with and without medroxyprogesterone acetate in early postmenopausal women. Osteoporos Int 16:372-379