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Women’s Health News: December, 4

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High-Dose HRT Still Prevalent

Eight years after the Women’s Health Initiative trial found that traditional hormone replacement therapy carried serious health risks for postmenopausal women, doctors continue to write prescriptions for it by the millions, researchers said.

According to data from a large, continuous survey of physicians, about 3.1 million visits in the U.S. in 2009 resulted in prescriptions for standard-dose estrogen therapy, alone or in combination with other hormones, according to a study published online in Menopause.

About one million of those prescriptions were for women 60 and older, the population most at risk for the cardiovascular and cancer risks identified in the Women’s Health Initiative study, noted Sandra A. Tsai, MD, MPH, of Stanford University in California, and colleagues.

“Despite reduced use, standard-dose oral menopausal hormone therapy remains the dominant formulation,” they wrote.

Overall, systemic hormone therapy for menopause symptoms has fallen by nearly two-thirds since 2001, Tsai and colleagues found, from about 16.3 million prescriptions to 6.1 million in 2009.

But low-dose oral preparations and vaginal and transdermal formulations — believed to carry less risk of adverse effects — still accounted for a minority of prescriptions.

“Greater recognition of distinctions based on menopausal hormone therapy dose, route of administration, need for concomitant progestogens, and woman’s age may move clinical practice into better alignment with available evidence,” the researchers concluded.

The study used data from 2001 to 2009 in the National Disease and Therapeutic Index, an ongoing survey of about 1,800 physicians who provide quarterly reports on their management of patients evaluated on two recent, randomly assigned workdays.

The reports list diagnoses and prescriptions written (as well as OTC products recommended) for each patient seen on those days. Consequently, the data is detailed enough to identify hormonal preparations prescribed for menopause symptoms.

In 2009, according to Tsai and colleagues, the database included about 341,000 patient encounters. The researchers extrapolated the results to the entire U.S. physician population to yield estimates of national hormone therapy prescription numbers.

Between the release of the Women’s Health Initiative results and 2009, the number of oral estrogen-only hormone prescriptions at standard doses declined 71%. Estrogen combined with other hormones at standard doses fell 83%.

Use of vaginal hormone formulations rose steadily from an estimated 2 million to 2.5 million prescriptions, whereas transdermal hormone prescriptions declined slightly, from 1.7 million to 1.5 million.

Tsai and colleagues identified differences in prescribing patterns according to physician specialty. Ob/gyns showed smaller declines over time in the percentage of visits that included menopausal hormone therapy prescriptions (46% from 2001 to 2009) compared with all other specialties (69%).

Of all visits resulting in a menopausal hormone therapy prescription, 72% were written by ob/gyns.

One of the most remarkable study findings, Tsai and colleagues suggested, was that low-dose oral therapy prescriptions did not make greater inroads into overall use of oral formulations during the study period.

Low-dose formulations, which have been found to be effective for controlling unwanted menopause symptoms, did increase from 700,000 to 1.3 million in 2009.

But this was still only 29% of all oral menopausal hormone therapy prescriptions, the researchers noted.

Moreover, use of low-dose products has been declining since hitting a peak of 1.5 million prescriptions.

“Current recommendations to use the lowest dose … effective for symptom relief should receive greater consideration,” they wrote.

They also expressed surprise that transdermal formulations have not gained in popularity during the study period.

Tsai and colleagues identified several limitations to the study. The survey excludes physicians in publicly funded practices, where lower income patients are more likely to be seen. Patients seen by respondent physicians may also not be representative of the general female population and their hormone therapy use.

In addition, information on symptoms and responses to previous therapies is sparse in the database.

As a result, the researchers noted, “there are inherent limitations in commenting on the appropriateness of current practice patterns.”

Study Adds Uterine Fibroids to Meningioma Risk Factors

MONTREAL – Meningiomas in postmenopausal women are associated with an increased rate of uterine fibroids, low levels of physical activity, and greater height and body mass index, according to an analysis of the Iowa Women’s Health Study.

The link with uterine fibroids is a novel finding, “probably due to shared risk factors,” commented Dr. Derek R. Johnson of the Mayo Clinic, Rochester, Minn. “I’m certainly not suggesting it’s causal,” he said at the annual meeting of the Society for Neuro-Oncology.

The Iowa Women’s Health study is a prospective cohort of women followed since 1986. Dr. Johnson’s analysis included 27,791 of these women who had completed a follow-up self-report survey in 1993, had no history of cancer, and were enrolled in Medicare.

The mean age of the women was 70 years (in 1993), and their mean body mass index (BMI) at the time of first enrollment was 27 kg/m2.

The analysis found 125 incident meningiomas reported over 291,021 person-years of follow-up, for an overall incidence of 43/100,000 person-years.

BMI was the strongest of the self-reported risk factors for meningioma, with a relative risk (RR) of 2.14 for BMIs greater than 30 compared with BMIs in the normal range of 19.5-24.5 kg/m2. BMI at age 50 and age 40 was positively associated with the risk of meningioma, but BMI at younger ages was not.

Height was the second strongest risk factor for meningioma, with a relative risk of 2.04 for height above 66 inches compared with height of 62 inches or shorter.

Physical activity was protective against meningioma. Compared with a low rate of physical activity, medium and high levels were associated with decreased risk (RR, 0.57 and 0.61).

A history of uterine fibroids carried a relative risk of 1.78, but no other reproductive factors seemed to be correlated. “Fibrocystic breast disease, endometriosis, and some other reproductive covariates have not shown any association, so, with uterine fibroids being so strongly associated, I think it’s not simply a coincidence,” Dr. Johnson said.

The associations were significant after adjustment for “current” BMI (1993).

The data raise the hypothesis that a metabolic environment associated with greater growth in adolescence, and greater weight later in life, may play a role in the etiology of meningiomas, he said.

“Potentially the key unifying factor in the things we found in meningioma risk is the influence of circulating sex hormones and insulin resistance,” Dr. Johnson said.

Meningiomas occur at twice the rate in women as in men, and the incidence is increasing, he added.

When asked for his opinion on the findings, Dr. Fred Barker of the department of neurosurgery at Massachusetts General Hospital, Boston, said the association with uterine fibroids was intriguing. “It is biologically plausible that the same mechanism of exposure to hormones could explain the association, but it may also be some genetic predisposition, or it may be that women who seek out imaging have both of these things found with relatively minor symptoms.”

Many meningiomas in elderly people are small and asymptomatic and are discovered only incidentally or on autopsy, he said in an interview. “As with fibroids, it could just be that certain patient behaviors lead to imaging being done.”

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