Long-term hormone therapy for perimenopausal and postmenopausal women

Long-term HRT is not indicated for routine prevention and management of chronic conditions in women. Since HRT is not common in many developing countries, this Cochrane review concerns very few women and health-care providers in selected urban settings in the developing world.

RHL Commentary by Seshadri L


This review focuses on the risks and benefits of long-term use of hormone therapy (HT); excluding short outcomes such as menopausal symptoms (e.g. hot flushes). Fifteen randomized-controlled trials involving 35 089 women aged 41–91 years were included. The review compared a placebo with HT with all estrogens (with or without progestogens) administered via oral, transdermal, subcutaneous or intranasal routes.

The reviewers found no increase in mortality from any cause from any form of HT. However, combined (estrogen plus progestogen) HT was associated with an increase in: venous thromboembolism and coronary events after one year of use; stroke after three years of use; and, gall bladder disease and breast cancer after five years of use.

Similarly, HT with estrogens alone caused an increase in the incidence of stroke and gall bladder disease in healthy postmenopausal older women. On the other hand, statistically significant reductions in the incidence of fractures and colon cancer were found in users of all types of HT.

The number of women in the trials varied widely, the largest number being in the Women's Health Initiative (WHI) trial and the second largest, the Heart and Estrogen/progestin Replacement Study (HERS) trial. The WHI had an overwhelming number of 16 608 women and therefore, the results of the review are largely determined by the results of this trial. As pointed out by reviewers, 11 of the 15 trials included women with a mean age of 55 years, three trials did not provide the mean age and one included women with a mean age of 48 years. Therefore, though the review is on the use of HT in perimenopausal and postmenopausal women, the results are largely applicable to postmenopausal women only. The only subgroup analysis conducted in the review involving women between 50 and 59 years found an increase in risk of venous thromboembolism, with the absolute risk being very small and higher in high-risk women.

A definite conclusion that can be drawn from the review is that HT is not indicated for the treatment of chronic diseases in older postmenopausal women. Search for the trials was thorough and the data were analysed using standard methods. Presentation of the data and findings is clear.


2.1. Magnitude of the problem

Traditionally, in developing countries, menopause and problems thereof are accepted as normal physiological phenomenon. Being heavily preoccupied with issues like communicable diseases, nutritional deficiencies, maternal mortality and perinatal mortality, health systems in developing countries have traditionally paid little attention to menopausal symptoms and its related problems. However, with increasing life expectancy among women in developing countries, the prevalence of osteoporosis, cardiovascular disease and problems of postmenopausal women continue to increase substantially. About 75% of world’s postmenopausal women live in these countries. Therefore, health problems related to the menopause are of a great magnitude. The actual prevalence rates of breast cancer, postmenopausal osteoporosis and other problems are not known. About 50% of women above the age 50 have been found to have osteoporosis by some authors (1). Currently, HT prescription is often limited to private clinics in urban settings. The reasons for this are several: (i) older women are marginalized as they are financially dependent on the family; (ii) HT is expensive; (iii) women have a mindset that does not allow them to interfere with nature; and (iv) women are too inhibited to seek relief for symptoms of menopause.

2.2. Applicability of the results

Most of the studies included in the review were conducted in Canada or the USA. There was one from Hong Kong, but none from the developing world. Therefore, it is difficult to generalize the results to women in developing countries who have different susceptibility and risk factors for chronic diseases. Unlike in developed countries, prescribing HT for asymptomatic older women has never been a common practice in the developing world; therefore, this review is unlikely to influence existing practices in developing countries.

2.3. Implementation of the intervention

Since HT is not common in developing countries the implementation of the findings of this review concern very few women and health-care providers in selected urban settings in developing countries.


Research on the prevalence and incidence of the various conditions that occur in peri- and postmenopausal women in developing countries is necessary to examine the magnitude of the problem.


  • Pande KC. Prevalence of low bone mass in healthy Indian population. Journal of Indian Medical Association 2002;100:598–600.

This document should be cited as: Seshadri L. Long-term hormone therapy for perimenopausal and postmenopausal women: RHL commentary (last revised: 6 Mars 2006). The WHO Reproductive Health Library; Geneva: World Health Organization.

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