COMMENTARY

December 2004: The Year in Review -- Ob/Gyn & Women's Health

Ursula Snyder, PhD

Disclosures

January 24, 2005

Gynecology - Menopausal Hormone Therapy

In 2004, the Women's Health Initiative (WHI) was in the news again with the termination of the estrogen only (ET) arm of the trial, because it provided no overall benefit for chronic disease prevention and increased the risk of stroke.[34] For interested readers, a detailed review and critique of this study arm and the estrogen plus progestin arm was published in Medscape General Medicine, Ob/Gyn & Women's Health section. (See also Medscape Medical Newsmaker Interview with lead investigator Jacques Rossouw, MD and Medscape Medical News CME story.) Two reports from the WHI Memory Study also found that ET did not reduce the incidence of dementia or mild cognitive impairment.[35,36] (See Medscape Medical News CME story.)

Another trial was terminated early this year: The "Hormonal replacement therapy after breast cancer diagnosis — is it safe?" (HABITS) trial was stopped when interim analysis showed increased risks of breast cancer recurrence for HRT users.[37] (See Medscape Medical News story.)

In response to the latest WHI results, the FDA proposed in February that manufacturers of HT products change the warning label to note increased risk of dementia and abnormal mammograms.[38] Of note is that perhaps the potential risks of menopausal hormone therapy could have been exposed much earlier if data from trials conducted by pharmaceutical companies had been made publicly available, according to an article in the British Medical Journal by British and Finnish researchers.[39]

According to the chair of the ACOG Task Force on Hormone Therapy, Isaac Schiff, MD, "Approximately 65% of women on [HT] stopped therapy after the [WHI] ...Two years later, reports suggest that about 1 in 4 women who stopped went back on it because it still offers the best relief for menopausal symptoms." On September 30, 2004, ACOG released its Hormone Therapy report , which provides state-of-the-art evidence-based clinical recommendations for use of HT.

Several studies published this year highlight risks and benefits associated with HT. A study by German researchers suggests that DNA microarray-based analysis of single nucleotide polymorphisms could be useful for the assessment of the relative risks and benefits of HT.[40]

HT may impair endothelial function in postmenopausal women who are taking the insulin-sensitizing agent rosiglitazone for type 2 diabetes.[41] In addition, HT has been associated with coronary atherosclerosis progression and exacerbation of the profile of inflammatory markers in women with abnormal glucose tolerance.[42] The authors conclude that HT is not warranted for use in diabetic women.

The estrogen component of oral HT is associated with ovarian cancer risk; the risk increases with cumulative oral estrogen intake as opposed to duration of therapy.[43]

HT may increase risk of asthma.[44] (See Medscape Medical News story.) It does not seem to reduce the risk or slow progression of cataracts.[45]

For certain women, however, using HT for a short time (2 years) may provide quality of life (QOL) benefits that outweigh the risks of cardiovascular disease (CVD).[46] Col and colleagues used a Markov simulation model and data obtained from the WHI to determine the effect of .estrogen plus progestin HT on QOL and quality adjusted-life expectancy (QALE) in 50 year-old women. They made the assumption that HT-affected QOL only during perimenopause, when it reduced symptoms by 80%. The results overall were as follows:

Among asymptomatic women, short-term HT was associated with net losses in life expectancy and QALE of 1 to 3 months, depending on CVD risk. Women with mild or severe menopausal symptoms gained 3 to 4 months or 7 to 8 months of QALE, respectively. Among women at low risk for CVD, HT extended QALE if menopausal symptoms lowered QOL by as little as 4%. Among women at elevated CVD risk, HT extended QALE only if symptoms lowered QOL by at least 12%.

This past year some research has suggested a possible benefit of testosterone in reducing the risk of breast cancer associated with conventional HT.[47,48,49] However, a number of studies published in 2004 have found endogenous levels of steroid hormones may increase breast cancer risk.[50,51,52,53,54] One of these studies showed a statistically significant direct association between breast cancer risk and the level of both estrogens and androgens.[50] A study led by board member Anne McTiernan, MD, PhD, showed that a 12-month exercise intervention led to declines in testosterone and free testosterone in sedentary, overweight postmenopausal women, ages 50 to 75 years, who were not using HT.[55]

Finally, much has been made that the mean age of the women in the WHI, 63 years, was high, perhaps too high, to assess possible benefits of HT, and that the benefits observed in earlier trials may have been in part because the women were younger when they initiated HT. The results of a meta-analysis of randomized controlled trials of HT to assess the effect of age on mortality associated with HT showed that total mortality was reduced for women younger than 60 years but not older.[56]

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