The Long-Term Risks and Benefits of Hormone Replacement Therapy

Abstract

Summary There is increasing awareness that the long‐term consequences of ovarian failure can be prevented or reduced with appropriate hormone replacement therapy (HRT). After the menopause, there is a rapid loss of trabecular bone resulting in a one in two lifetime risk of osteoporotic fracture. HRT prevents this bone loss and decreases the incidence of fracture. A minimum of 5 years treatment is recommended for significant benefit. Epidemiological evidence is accumulating that post‐menopausal oestrogen therapy reduces the risk of cardiovascular disease and stroke by between 30 and 70% even in the presence of established risk factors. Given the prevalence of cardiovascular disease, this is likely to be one of the principle benefits of HRT in the next decade. Concerns about the long‐term safety of HRT have focused on endometrial and breast cancer. The increase in risk of endometrial cancer associated with oestrogen only therapy is abolished with the sequential addition of a progestogen for 10–12 days each cycle. The possible effect of HRT on breast cancer risk has to be considered against the background of a one in 12 lifetime risk of developing this disease. The epidemiological studies investigating this relationship are reviewed in this paper. There is a broad consensus that 5–6 years duration of HRT does not increase breast cancer risk. Longer durations of therapy (10–15 years) have been reported to increase this risk although not all the data are in agreement. Other factors, such as family history and benign breast disease, may also influence the risk of breast cancer. The potential benefits of HRT on mortality and morbidity are enormous. Against this is a possible small increase in breast cancer risk with long‐term usage. Greater awareness of the long term consequences of the menopause and the potential benefits of HRT should be encouraged so that women can make informed decisions about their need for HRT.

A naturally occurring naringenin derivative exerts potent bone anabolic effects by mimicking oestrogen action on osteoblasts

“…However, the benefits of E2 replacement therapy (ERT) against post‐menopausal osteopenia are offset by the increased risk of breast and uterine cancers (Maggio, 1980; Steinberg et al ., 1991; Lobo, 1995; Langer et al ., 2003). Consequently, there is a growing interest in assessing the role of phytoestrogens in the prevention of post‐menopausal osteoporosis because of their apparent lack of the adverse effects commonly associated with ERT (Hillard et al ., 1991; Lien and Lien, 1996; Delmas, 1999; Carusi, 2000; Arjmandi, 2001; Ishimi, 2006; Coxam, 2008; Sharan et al ., 2009).…”

Aging Reduces the Efficacy of Estrogen Substitution to Attenuate Cardiac Hypertrophy in Female Spontaneously Hypertensive Rats

“…Observational studies initially suggested a protective function of postmenopausal hormone replacement therapy (HRT) against heart disease with risk reductions of Յ35% to 50%. 2 But controlled clinical end point studies, such as Heart and Estrogen/progestin Replacement Study (HERS) and the recently terminated Women's Health Initiative (WHI) trial, reported no protective function of HRT consisting of conjugated equine estrogens plus medroxy-progesterone-acetate for the primary or secondary prevention of coronary artery disease. 3 In contrast, estrogen supplementation in animal models of human heart disease was mostly associated with beneficial hormone effects.…”

Therapeutic Potential of the Endocannabinoid System in the Brain

“…The endocannabinoid system plays a modulatory role in several physiological processes, mainly in the brain [4,6,38] although also in peripheral processes such as the immune regulation [39], the cardiovascular system [40], the reproductive endocrine processes [41], and the control of energetic metabolism [42]. In the brain, endocannabinoids participate in processes such as the control of movement [43,44], learning and memory [45] and nociception [46], as …”