More bad news this week relating to the use of estrogen/progestin combination hormone replacement therapy (HRT). In this week’s Journal of the American Medical Association (JAMA), another report from the large-scale prospective Women’s Health Initiative hangs the crepe on the continued use of combination HRT. A total of 16,608 postmenopausal women without evidence of cancer were randomly assigned to take combined HRT or placebo pills. These women were then followed from 1993 to 1998 at 40 different participating medical centers. Screening mammograms and breast examinations were performed upon entry into the study and yearly thereafter. At the end of this very short period of follow-up, the study determined that combined HRT, over the course of 5 years, resulted in a 24% relative increase in the incidence of breast cancer when compared to the women taking only sugar pills. As if this were not bad enough news already, the women who were taking the HRT pills tended to develop significantly larger and more advanced breast cancers than did the women who took only placebos. Especially worrisome was the finding that after only 1 year of combination HRT, the percentage of women with abnormal mammograms was significantly higher among the women receiving HRT when compared to the women not taking HRT pills (9.4% vs. 5.4%, respectively). This HRT-related effect on mammographic abnormalities persisted throughout the 5-year study.

Over the past year, the scientific news regarding the potentially harmful effects of combined HRT has been universally bad. Regular readers of this column already know of the myriad adverse health effects now being linked to combination HRT use, including many diseases (such as cardiovascular disease and dementia) that the manufacturers of HRT pills have long insisted were actually reduced in incidence with HRT. As non-HRT treatments for the transient emotional and thermoregulation symptoms that distress some postmenopausal women continue to improve, there is no doubt in my mind but that combined HRT therapy will no longer be considered safe or medically appropriate therapy. For women who still have their uterus, HRT with estrogen alone is not an option due to the resulting increase in the risk of developing uterine cancer.

Effects of Long-term Hormone Replacement Therapy

Another study reported in the current issue of JAMA looks at the impact of long-term HRT, both combined HRT and estrogen alone. A total of 975 women, aged 65 to 79 years, and diagnosed with breast cancer between April 1997 and May 1999, were included in this study. The HRT history of these 975 women with newly diagnosed breast cancer was carefully documented. The study found that the women who used estrogen-alone HRT (all of whom had previously undergone hysterectomy), even for 25 years or longer, did not appear to experience a significantly increased risk of developing breast cancer (although a small increase in the risk of breast cancer from long-term estrogen use could not be excluded in this study). On the other hand, women who had used combination HRT at any time in the past had, as a group, a 70% increase in the relative risk of developing breast cancer. The increase in the risk of developing a specific type of breast cancer, infiltrating lobular breast cancer, was 170% among women with a history of prior combination HRT use. The risk of developing breast cancer continued to climb with increasing durations of combination HRT. This increase in breast cancer risk seen with combined HRT used did not vary between women who took progestin pills every day and those who took the pills for only 7 to 10 days per month. Ladies (and gentlemen), it is time for combined HRT to end.

The Mediterranean Diet & Health

As the battle between different diet camps continues to rage on, despite the recent death of high-fat low-carbohydrate guru Robert Atkins, a new study in this week’s New England Journal of Medicine shines the investigative spotlight on the venerable “Mediterranean Diet.” It has long been observed that, despite a penchant for smoking and frequent wine consumption, people in Mediterranean Europe who adhere to a diet rich in fish, poultry, olive oil, fruits and vegetables (and regular but moderate red wine intake) appear to have a lower risk of dying from cardiovascular disease. This newly reported study looked at more than 22,000 adults in Greece, examining the dietary habits of each study participant. This cohort of study participants was then followed for an average of 44 months. The study found that people who adhered the closest to the traditional Mediterranean diet had a 25% smaller relative risk of dying than people who did not follow such a diet. Reduction in death due specifically to coronary heart disease was 33% among adherents to the Mediterranean diet, while death due to cancer was reduced by 25% among the folks who adhered to the Mediterranean diet. While no single food item within the standard Mediterranean diet appeared to confer any significant protection against disease or death, the cumulative health benefits of the Mediterranean diet, as a whole, appear to be very significant.

Dr. Robert A. Wascher