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Menopause Matters

NAMS Publishes Hormone Therapy Recommendations

Wulf H. Utian, MD, PhD

When investigators for the Women's Health Initiative (WHI) trial—the large, randomized, placebo-controlled clinical trial of postmenopausal hormone therapy (HT)—prematurely terminated the estrogen plus progestin therapy (EPT) arm in mid-2001 because of identified and potential risks, it sent shockwaves through the field of menopause-related health care. Since then, a plethora of articles on HT have been published in both the medical and lay press—and confusion has ensued.

To help clarify the role of estrogen therapy (ET) and EPT in perimenopausal and postmenopausal women, The North American Menopause Society (NAMS) reviewed the data and announced clinical recommendations in September 2002.¹ Additional data from the WHI and other significant trials published since then have substantially altered the view toward HT. The North American Menopause Society responded with an updated set of recommendations.² This column presents some of the latest recommendations from that statement.

the NORTH AMERICAN MENOPAUSE SOCIETY HORMONE THERAPY RECOMMENDATIONS

First, NAMS has urged all in clinical practice, research, and the media to standardize terminology (see Box on page 55), knowing that this step is essential for accurate communication.

The North American Menopause Society recommends the following indications for HT:

• Treatment of moderate to severe menopause symptoms (eg, hot flashes, sleep disturbances) remains the primary indication for systemic ET/EPT. When hormones are considered solely for vulvar and vaginal atrophy, local ET is preferred.
• Chronic progestogen use continues to be reserved primarily for endometrial protection. Although some women may have adverse side effects from progestogen, EPT regimens other than continuous-sequential (CS-EPT) and continuous-combined (CC-EPT) are not recommended, owing to lack of long-term endometrial safety data.
• There is definitive evidence for EPT efficacy in reducing the risk of postmenopausal osteoporotic fracture; there is no comparable evidence for ET. However, because of the potential risks associated with ET/EPT, alternative osteoporosis therapies should also be considered. Importantly, clinicians are reminded that there are no long-term data regarding the osteoporosis effectiveness of HT or bone-specific drugs. Also, the effects of HT on the risk of osteoporotic fracture in perimenopausal women have not been established in randomized, clinical trials.

The North American Menopause Society does not recommend HT for the following indications:

• EPT should not be used for primary or secondary prevention of coronary heart disease or stroke. The effect of ET is not yet clear; therefore, ET should not be used for these indications unless confirming data are available.
• Initiating EPT after age 65 years cannot be recommended for the primary prevention of dementia. Evidence is insufficient to either support or refute the efficacy or harm of ET/EPT for primary prevention of dementia when therapy is initiated during perimenopause or early postmenopause. The use of ET/EPT does not appear to convey direct benefit or harm for secondary prevention of dementia due to Alzheimer's disease.

The North American Menopause Society emphasized that not all data apply to all women:

• WHI data should not be extrapolated to women experiencing premature menopause and initiating HT at that time.
• WHI data should be extrapolated only with caution to women younger than age 50 years who initiate HT at that time.

The North American Menopause Society addressed the association of HT and breast cancer risk as follows:

• In postmenopausal women, breast cancer risk is increased with ET and, to a greater extent, EPT use beyond 5 years. Progestogen appears to contribute to that adverse effect. However, insufficient data exist to determine whether ET/EPT is associated with any increase in mortality due to breast cancer.
• In perimenopausal women, the effects of HT on risk for breast cancer have not been established in randomized clinical trials.
• EPT and, to a lesser extent, ET increase breast cell proliferation, breast pain, and mammographic density, possibly impeding the diagnostic interpretation of mammograms.

The North American Menopause Society addressed the magnitude of risks associated with HT:

• The absolute risks published thus far regarding HT are small, as are the benefits for bone and reduction in colon cancer risk.
• For women younger than age 50 years or those at low risk for coronary heart disease, stroke, osteoporosis, breast cancer, or colon cancer, the absolute risk or benefit from EPT is likely to be smaller than demonstrated in the WHI, although the relative risk may be similar.

The following clinical considerations were recommended:

• Prior to starting any therapeutic regimen, all women should have a complete health evaluation. An individual risk profile is essential for every woman contemplating any regimen of ET or EPT. Women should be informed of known risks.
• Use of ET/EPT should be limited to the shortest duration consistent with treatment goals, benefits, and risks for the individual woman, taking into account symptoms and domains that may have an impact on quality of life.
• Lower than standard doses of ET/EPT should be considered. Compared with standard doses, many studies have demonstrated nearly equivalent vasomotor and vulvovaginal symptom relief and preservation of bone mineral density. Lower doses are better tolerated and may or may not have a more positive safety profile, although they have not been tested for outcomes (including endometrial safety) in long-term trials.
• Nonoral routes of ET/EPT administration may offer advantages and disadvantages, but the long-term benefit-risk ratio has not been determined. Transdermal ET appears to offer advantages versus oral ET, including not increasing C-reactive protein or triglyceride levels and having a lower risk of deep venous thrombosis.

The North American Menopause Society has advised that extended use of HT is acceptable under the following circumstances, provided that the woman is well aware of the risks and she is under strict clinical supervision:

• For the woman for whom, in her opinion, benefits of symptom relief outweigh risks, notably after failing an attempt to withdraw HT. However, attempts should be made over time to reduce and cease HT.
• For the woman with moderate to severe menopause symptoms who are at high risk for osteoporotic fracture. However, attempts should be made over time to lower the dose or cease HT and introduce alternate bone-sparing therapy.
• For the prevention of osteoporosis in a woman at high risk when alternate therapies are not appropriate.

To view the full report or to obtain more and ongoing information about menopause, visit the NAMS Web site (www.menopause.org).

Wulf H. Utian, MD, PhD, is Arthur H. Bill Professor Emeritus of Reproductive Biology and Obstetrics and Gynecology, Case Western Reserve University School of Medicine; President, Rapid Medical Research; Consultant in Women's Health, Cleveland Clinic Foundation, Cleveland, Ohio. Dr. Utian is Executive Director and Honorary Founding President of The North American Menopause Society. He was NAMS President from 1989 to 1992 and has been a member of the Board of Trustees since 1989.

References

1. The North American Menopause Society. Amended report from the NAMS Advisory Panel on Postmenopausal Hormone Therapy. Menopause. 2003; 10(1):6-12.
2. The North American Menopause Society. Estrogen and progestogen use in peri- and postmenopausal women: September 2003 Position Statement of The North American Menopause Society. Menopause. 2003;10(6):497-506.

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