Hormone Replacement Therapy

There is probably no medical topic more controversial than hormone replacement therapy (HRT). For many years, women have had the choice of taking medications to replace the female hormones that are not produced naturally by the body after menopause. HRT may involve taking estrogen alone, or in combination with progesterone (or progestin in its synthetic form). Until about 2003, it was thought that HRT was beneficial for most women, and results from several studies were positive. But results from the Women’s Health Initiative research in the United States and the Million Women Study in the United Kingdom indicated that for some types of HRT there were several potentially very serious side effects. Consequently, physicians are now far more cautious in recommending HRT.

The Women’s Health Initiative (WHI), begun in the United States in 1991, was a very large study (National Heart, Lung, and Blood Institute, 2003). The postmenopausal hormone therapy clinical trial had two parts. The first involved 16,608 postmenopausal women with a uterus who took either estrogen plus progestin therapy or a placebo. The second involved 10,739 women who had a hysterectomy and were taking estrogen alone or a placebo.

The estrogen plus progestin trial used 0.625 milligram of estrogens taken daily plus 2.5 milligrams of medroxyprogesterone acetate taken daily (Prempro). This combination was chosen because it is the mostly commonly prescribed form of the combined hormone therapy in the United States, and, in several observational studies, it had appeared to benefit women’s health. The women in the WHI estrogen plus progestin study were aged 50 to 79 when they enrolled in the study between 1993 and 1998. The health of study participants was carefully monitored by an independent panel called the Data and Safety Monitoring Board (DSMB). The study was stopped in July 2002 because investigators discovered a significant increased risk for breast cancer and that overall the risks outnumbered the benefits. However, in addition to the increased risk of breast cancer, heart attack, stroke, and blood clots, HRT resulted in fewer hip fractures and lower rates of colorectal cancer.

The Million Women Study began in 1996 and included 1 in 4 women over age 50 in the United Kingdom, the largest study of its kind ever conducted. Like the Women’s Health Initiative, the study examined how HRT (both estrogen/progestin combinations and estrogen alone) affects breast cancer, cardiovascular disease, and other aspects of women’s health.

Results from these large-scale studies are confusing (Shapiro,

2007) . An overview of the results based on what type of HRT women were taking is presented in Table 3.4.

A newer approach to HRT involves a class of compounds called selective estrogen receptor modulators (SERMs), which can be considered "designer estrogens," each of which has its own way of acting and so must be evaluated individually (Shelly et al., 2008). SERMs have the protective properties of estrogen on bone tissue and the cardiovascular system and seem to block some estrogen effects on breast tissue. However, there is some evidence that they may stimulate growth of uterine cells, slightly increasing the risk of uterine cancer, or may cause hot flashes. In essence, they have the advantages of traditional HRT with fewer negative side effects. Two SERMs that have been approved for use in preventing breast cancer and are being intensively studied are tamoxifen and raloxifene, with others in development (National Cancer Institute, 2007).

In sum, women have difficult choices to make when deciding whether to use HRT to combat certain symptoms related to menopause and to protect themselves against other diseases. To date, research evidence about the long-term risks of HRT is clear in the case of the most common estrogen – progesterone combination.

The best course of action is to consult closely with one’s physician to weight the benefits and risks.

92 CHAPTER 3

Table 3.4

Benefits and Risks of HRT Therapy

Women with a Uterus Estrogen + Progestin

Women Without a Uterus* Estrogen Only

BENEFITS

Relieves hot flashes/night sweats

Yes

Yes

Relieves vaginal dryness

Yes

Yes

Reduces risk of bone fractures

Yes

Yes

Improves cholesterol levels

Yes

Yes

Reduces risk of colon cancer

Yes

Don’t know

RISKS

Increases risk of stroke

Yes

Yes

Increases risk of serious blood clots

Yes

Yes

Increases risk of heart attack

Yes

No

Increases risk of breast cancer

Yes

Possibly

Increases risk of dementia, when begun by women age 65 and older

Yes

Yes

Unpleasant side effects, such as bloating and tender breasts

Yes

Yes

Pill form can raise level of triglycerides (a type of fat in the blood)

Yes

Yes

*Women who have had a hysterectomy and have had their uterus removed.

Source: National Institute on Aging (2006); http://www. niapublications. org/tipsheets/hormones. asp.

is evidence that estrogen and progesterone influ­ence the brain mechanisms that underlie learning and memory, the value of hormone replacement therapy as a treatment or deterrent for cognitive impairment remains largely unknown (Dohanich,

2003) . For these reasons, as discussed in the Current Controversies feature, probably no other area of medical research has resulted in more contradictory data about the potentially serious side effects (or lack thereof) than has work on hormone replace­ment therapy.

Women’s genital organs undergo progressive change after menopause (Aldwin & Gilmer, 2004).

The vaginal walls shrink and become thinner, the size of the vagina decreases, vaginal lubrication is reduced and delayed, and the external genitalia shrink somewhat. These changes have important effects on sexual activity, such as an increased pos­sibility of painful intercourse and a longer time and more stimulation needed to reach orgasm. Failure to achieve orgasm is more common in midlife and beyond than in a woman’s younger years. However, maintaining an active sex life throughout adulthood lowers the degree to which problems are encoun­tered. Despite these changes, there is no physi­ological reason not to continue having an active and

Physical Changes 93

enjoyable sex life from middle age through late life. The vaginal dryness that occurs, for example, can be countered by using personal lubricants, such as K-Y or Astroglide.

Whether women continue to have an active sex life has a lot more to do with the availability of a suitable partner than a woman’s desire for sexual relations. This is especially true for older women. The AARP Modern Maturity sexuality study (AARP, 1999a) and the Sex in America study (Jacoby, 2005) found that older married women were far more likely to have an active sex life than unmarried women. The primary reason for the decline in wom­en’s sexual activity with age is the lack of a willing or appropriate partner, not a lack of physical ability or desire (AARP, 1999a; Jacoby, 2005).