Hormone therapy following menopause

Estradiol transdermal patches are used to treat the symptoms of menopause.
Estradiol transdermal patches are used to treat the symptoms of menopause.

At a glance

  • The risk/benefit ratio is highest in younger women who begin hormone therapy (HT) not long after menopause.
  • HT is approved for two indications: relief of vasomotor symptoms and prevention of osteoporosis.
  • Research suggests that HT may be beneficial for preventing diabetes, improving mood, or avoiding urinary tract problems.
  • Using HT long beyond menopause carries increased risks, which, for some women, may be outweighed by the benefits.

Controversy has long surrounded hormone therapy (HT) after menopause. The debate intensified in 2002 when reports from the Women's Health Initiative (WHI) suggested that HT increased risk of heart disease and breast cancer in certain populations. The importance of the issue led The North American Menopause Society to publish a position statement on HT that year and to revise it four times since, most recently in July 2008.
“It's a rapidly evolving area of women's health,” says Wulf H. Utian, MD, PhD, executive director of the society and consultant in women's health at Cleveland Clinic in Ohio. “And because there's so much confusion and misinformation out there, we feel an absolute need to provide reliable and trustworthy summaries of the current state of knowledge.” 
 

Age matters

The position statement stresses the need to consider the individual's characteristics when weighing the risks and benefits of HT. Age is particularly important: It has become increasingly evident that the risk/benefit ratio is highest in younger women who begin HT not long after menopause and that the ratio declines with age and years beyond menopause. The authors caution against extrapolating findings from large studies (such as WHI) to populations different from the study group, particularly younger women.

In light of their elevated baseline risk of coronary heart disease (CHD), stroke, venous thromboembolism (VTE), and breast cancer, women older than 60 who experienced menopause at the typical age should not be given HT for the first time “without a compelling indication and only after appropriate counseling,” the authors say.

Early menopause, whether natural or the result of surgery, accentuates the age factor. Younger women are at reduced risk of breast cancer but subject to earlier onset of CHD and osteoporosis. Although data are limited, it appears that HT-associated risks are lower and benefits potentially greater for these women than for those who initiate HT at or after typical menopause age, the authors say.   

Approved indications

HT is approved for two indications: relief of vasomotor symptoms and prevention of osteoporosis.

Menopause-related symptoms: The treatment of vasomotor symptoms (hot flushes and night sweats) is the primary indication for HT. Estrogen, with or without progestogen, treats this condition effectively and ameliorates such consequences as insomnia and irritability; all systemic HT products have FDA approval for vasomotor symptom relief.

Estrogen is also the most effective treatment for vaginal dryness, dyspareunia, and other symptoms of vulvar and vaginal atrophy; all topical and many systemic estrogen and estrogen-progestogen preparations are approved for this indication. One systemic estrogen product is approved for painful intercourse per se, but the authors do not recommend HT for other sexual dysfunction.

Osteoporosis: Long-term treatment with some systemic estrogen-containing products is approved for the prevention of osteoporosis. Although none is approved for its treatment, the authors note that evidence from randomized, controlled trials (RCTs) indicates that HT can reduce postmenopausal fractures, even in women without osteoporosis.

Other uses

Research has suggested that HT may be beneficial for preventing diabetes, improving mood, or avoiding urinary tract problems.

Diabetes prevention: Several large RCTs suggest that HT reduces the incidence of type 2 diabetes mellitus (by 21% in one trial, 12% in another), and data from meta-analyses find an association with improved insulin resistance. There are also data indicating that estrogen may reduce the dosage of medication needed by postmenopausal women with diabetes.

Although HT is not recommended solely for diabetes prevention or treatment, this data “might be taken into account” when counseling at-risk women, Dr. Utian says. Most importantly, diabetes should no longer be considered a contraindication for HT.

Psychiatric issues: Evidence on mood and depression is mixed. The authors conclude that while HT might have positive mood effects (particularly during perimenopause), it should not be considered an antidepressant.
Data concerning cognition, memory, and dementia risk reduction are similarly inconsistent; HT cannot be recommended to enhance cognitive function or prevent impairment, the authors say.

Urinary health: Local estrogen may improve urge incontinence in the context of vaginal atrophy, but systemic HT appears to worsen stress incontinence. There is evidence that local estrogen lowers the risk of recurrent UTIs.

Risks

The risks that started the debate over HT focus on a woman's cardiovascular health and cancer.

Cardiovascular effects: Combined data from observational and randomized clinical trials (WHI included) suggest that CHD risk may decline when HT is first prescribed to women in their 50s, not long after menopause. On the other hand, CHD risk may increase if HT is initiated more than 10 years postmenopause. HT is not recommended for coronary protection at any age.

In addition, HT does not reduce stroke risk and may increase it in older women, albeit slightly. There is evidence linking oral HT with increased incidence of VTE.

Cancer: Breast cancer risk seems unaffected when estrogen is used for fewer than five years; the risk increases when combined estrogen-progestogen is taken for more than five years, but breast cancer remains rare.

Women with an intact uterus should use concomitant progestogen when taking estrogen to negate increased risk of endometrial cancer.

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