Posljednjih 20 godina primjena hormonskog nadomjesnog liječenja postala je uobičajna u perimenopauzi i postmenopauzi.

Racionalni stav je da se nadomjesna hormonska terapija propiše ženi koja je dobro informirana o potencijalnim opasnostima i koja ima smetnje koje smanjuju kvalitetu njezinog života. Sjeverno Američko Udruženje za Menopauzu (NAMS) donosi smjernice.

North American Menopause Society Issues Guidelines on Hormone Therapy CME/CE

February 26, 2010 – The benefit-risk ratio for menopausal hormone therapy (HT) is favorable for women beginning HT close to menopause but decreases in older women and with time since menopause in previously untreated women, according to the latest evidence-based position statement of the North American Menopause Society (NAMS), posted online February 16 and will be published in the March/April issue of Menopause.

“From a clinical perspective, the latest NAMS position statement on HT considers the current best practice of medicine,” NAMS Executive Director Margery L. S. Gass, MD, NCMP, said in a news release. “The Panel of world famous authorities clarified a broad spectrum of topics related to HT benefits and risks for postmenopausal women.”

Development of the Guidelines

The goal of the latest guidelines was to update clinicians as well as the lay public regarding NAMS’ recommendations for menopausal HT for postmenopausal women, considering the therapeutic benefit-risk ratio at various times through and beyond menopause.

An advisory panel of 17 clinicians and researchers with special expertise in HT reviewed each section of the previous position statement, published by NAMS in July 2008, in light of new studies and findings, and reached consensus on recommendations. The NAMS board of trustees then approved the updated official position statement, which highlights recent evidence regarding risks for breast cancer, cognitive dysfunction and decline, dementia, coronary heart disease (CHD), and stroke, as well as new recommendations regarding discontinuing HT.

The updated guidelines also include new sections on HT and ovarian and lung cancer, a listing of areas that vary from the 2008 position statement, and a suggested bibliography of key references published since the last statement.

The American Medical Women’s Association, the Asociación Mexicana para el Estudio del Climaterio, the Endocrine Society, Healthy Women (formerly the National Women’s Health Resource Center), the National Association of Nurse Practitioners in Women’s Health, and the Society of Obstetricians and Gynaecologists of Canada all had representatives participating fully in the editorial process and have endorsed the newest NAMS position statement.

“Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered,” the statement authors write. “Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable for women who initiate HT close to menopause but decreases in older women and with time since menopause in previously untreated women.”

The Women’s Health Initiative (WHI) trial of estrogen therapy (ET) offered evidence of considerable safety for 0.625 mg/day of oral conjugated estrogen, supporting the position that at least for this form of HT, the potential absolute risks are low.

In the WHI trial of combined estrogen-progestogen therapy (EPT), most risks were determined to be rare, using the criteria of the Council for International Organizations of Medical Sciences, except for stroke, which was above the rare category.

“For women younger than age 50 or those at low risk of CHD, stroke, osteoporosis, breast cancer, or colon cancer, the absolute risk or benefit from ET or EPT is likely to be even smaller than that demonstrated in the WHI, although the relative risk at different ages may be similar,” the statement authors write. “There is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects. Further research remains essential.”

Cancer and HT

Evidence to date is conflicting regarding the role of HT and risk for ovarian cancer, with no association or a modest increase in most epidemiologic studies, but with an association between HT use and increased ovarian cancer risk based on a relatively large volume of observational trial data. The statement suggests that the association between ovarian cancer and HT beyond 5 years, if any, should be considered as rare or very rare, but that women with a positive family history or other increased risk for ovarian cancer should be counseled about this rare association.

Overall data, including those from WHI analysis, suggest that starting EPT in older women with a positive smoking history may promote the growth of existing lung cancers. In contrast, evidence from the WHI and some case-control and cohort studies suggests that use of HT in women younger than 60 years offers some protection against lung cancer.

Although safety of EPT in survivors of breast cancer is controversial, with observational studies suggesting that it is safe and possibly even protective against recurrence, a randomized controlled trial showed a statistically significant 2.4-fold increase in new breast cancer events. ET use in breast cancer survivors has not been proven to be safe and may be associated with an increased risk for recurrence.

Cognitive Impairment, CHD, and HT

For the sole or main indication of preventing cognitive aging or dementia, the statement does not recommend HT at any age, and HT is actually linked to increased incidence of dementia when started in women age 65 years and older. Available data do not adequately address whether HT started soon after menopause increases or decreases later dementia risk, and limited evidence does not support the use of HT as a treatment of Alzheimer’s disease.

In terms of cardiovascular effects, the statement authors note that HT is currently not recommended as a sole or main indication for coronary protection in women of any age. Starting HT by age 50 to 59 years or within 10 years of menopause to treat typical menopausal symptoms does not seem to increase the risk for CHD events, and there is some recent evidence that starting ET in early postmenopause may lower CHD risk.

Findings of observational studies have been inconsistent regarding stroke risk with HT. The Nurses Health Study and WHI showed an increased risk for ischemic stroke, but other studies showed no effect on stroke risk.

Current data suggest that when HT is either tapered or abruptly discontinued, rates of vasomotor symptom recurrence are similar. The statement therefore makes no recommendation concerning how to discontinue therapy.

“When HT is desired by patients, individualization of therapy is key to providing health benefits with minimal risks, thereby enhancing [quality of life],” the statement authors conclude. “Women should be informed of known risks, but it cannot be assumed that benefits and risks of HT apply to all age ranges and durations of therapy. A woman’s willingness to accept risks of HT will vary depending on her individual situation, particularly whether HT is being considered to treat existing symptoms or to lower risk for osteoporotic fractures that may or may not occur.”

Financial disclosures of the statement authors are available online at the end of the position statement.

Menopause. 2010;17:242-255.

Additional Resource

More information on menopause is available on the womenshealth.gov Web site.

Clinical Context

The use of HT has changed greatly in the last decade, with a large number of women discontinuing use of this treatment after publication of the results of the WHI. Nonetheless, new analyses of that trial as well as insight from other epidemiologic and clinical studies have demonstrated important nuances of HT. The current position statement from the NAMS accounts for this new data and updates previous recommendations from 2006.

Study Highlights

  • ET, with or without a progestin, is the most effective therapy for menopause-related vasomotor symptoms.
  • Local vaginal ET is preferred vs systemic therapy when women complain only of urogenital symptoms of menopause. HT can alleviate dyspareunia, and local treatment may relieve urge incontinence and reduce the risk for urinary tract infection. However, systemic HT could worsen stress incontinence.
  • HT does not appear to have a significant effect on body weight.
  • HT can help prevent osteoporosis and fracture, but clinicians and patients should consider that the positive effects of HT on bone mass generally reverse quickly after discontinuation of treatment.
  • The risk for CHD associated with HT appears most profound among women who initiate treatment 10 years or more after menopause. Younger women might experience a lower risk for CHD with HT. Longer duration of HT among these women closer to menopause may further reduce the risk for CHD.
  • There are mixed data regarding the effect of HT on the risk for stroke.
  • Observational studies and randomized trials support a higher risk for venous thromboembolism associated with HT.
  • Large randomized controlled trials have suggested a lower risk for incident diabetes among women receiving HT. Transdermal ET may be advantageous among women with diabetes because this delivery system is less likely than oral therapy to increase triglyceride levels and thrombotic factors.
  • Estrogen-progestin HT increases the risk for breast cancer after 3 to 5 years of use, and this therapy also increases breast density. However, ET without progestin was not demonstrated to increase the risk for breast cancer in the WHI.
  • Most epidemiologic studies of HT and the risk for ovarian cancer demonstrate no effect or a modest increase in cancer risk associated with HT.
  • HT does not improve memory or cognition among women older than 65 years, and no trial has addressed the cognitive effects of long-term HT use among younger women.
  • The WHI suggested that the total mortality rate may be improved if HT is initiated shortly after menopause.
  • Regarding specific recommendations for the use of HT, the authors recommend using the lowest dose possible to achieve treatment goals.
  • There is no clear benefit of 1 route of administration of HT vs another.
  • The authors do not provide a firm recommendation regarding the duration of use of HT, and the decision regarding how long to continue therapy is best left to the patient and clinician.
  • Tapering HT does not appear superior to abrupt discontinuation of treatment in the recurrence of patient symptoms.

Clinical Implications

  • The current position statement finds that HT may alleviate vasomotor symptoms of menopause, urogenital symptoms and urge incontinence, and the risk for incident diabetes. However, HT does not appear to have a significant effect on body weight or cognitive ability.
  • The current position statement states that HT should be prescribed at the lowest possible dose to achieve treatment goals. There is no firm recommendation regarding the duration of use of HT, and tapering of HT appears unnecessary when it is decided to discontinue treatment.