Health Briefs

January 14, 2004

RECENT TRENDS IN HORMONE REPLACEMENT THERAPY (HRT)

Regular readers of this column are well aware of the recent finding by the huge Women’s Health Initiative Study (WHIS) that estrogen/progestin HRT is associated with a 26% increase in the risk of breast cancer.  Moreover, long-term use of combined HRT was also found to be associated with a 41% increase in the risk of strokes, a 20% increase in the risk of heart attacks, and a two-fold increase in the risk of potentially life-threatening blood clots.  (Also noted were a 37% decrease in the incidence of colorectal cancer and a one-third reduction in the risk of hip fractures.)  A doubling in the incidence of dementia (including Alzheimer’s disease) in older women has also been associated with chronic combination HRT use.  Much of this information was published in the summer of 2002 in the Journal of the American Medical Association.  One might therefore wonder what the impact of this information has been on the use of combined HRT in the United States since the release of this landmark study in 2002.

A study published in the current issue of the Journal of the American Medical Association evaluated the HRT prescribing habits of US physicians by reviewing two comprehensive prescription databases (the National Prescription Audit database and the National Disease & Therapeutic Index database).  These databases reflect prescriptions filled by retail pharmacies, and the patient office visits associated with these prescriptions, respectively.  The authors retrospectively reviewed the records of these databases, and analyzed the HRT prescription data from 1995 to July 2003.  The study found that annual HRT prescriptions increased from 58 million in 1995 to 90 million in 1999.  Combination HRT medications, which include both an estrogen and a progestin, accounted for most of this growth in annual HRT prescriptions.  Prempro, in particular, was the most common combination HRT medication prescribed.  (Gynecologists wrote more than 70% of all HRT prescriptions.)  After 1999, the annual HRT prescription rate then remained stable through June 2002.

Following publication of the interim WHIS results in July of 2002, HRT prescriptions began to decline in subsequent months.  When compared to the January-June 2002 timeframe, there was a 66% reduction in Prempro prescriptions and a 33% reduction in Premarin (a pure estrogen HRT) prescriptions during the January-June 2003 timeframe.  Small increases in vaginal estrogen cream and low-dose Premarin prescriptions were also noted following publication of the WHIS results.  Thus, it does appear that physician prescribing activity for HRT medications, and for combined estrogen/progestin medications in particular, have been significantly impacted upon by the WHIS results.  More recently, however, there is evidence of an upswing in HRT prescriptions once again, as postmenopausal women who stopped their HRT in the wake of the WHIS findings decide to resume taking their HRT medications despite the apparent risks of doing so.

Although they deny it, tobacco companies, in their unceasing quest to addict a new generation of potential customers to their products, advertise low-tar “light” cigarettes as being potentially healthier than the “standard-tar” varieties.  Their theory is that by reducing the carcinogen-rich tar component of their products (which, by the way, also reduces the nicotine content of the cigarette), a smaller load of cancer-producing chemicals will be ingested by people smoking these cigarettes.  However, it is in fact the nicotine content of cigarettes (and its bioavailability when being smoked) that really matters to smokers.  Although completely legal in all 50 states, nicotine is a profoundly addictive chemical, on par with cocaine and heroin (yes, another potentially addictive drug, alcohol, is also legal in the US).  Getting back to the point of a new study in the British Medical Journal, previous studies have demonstrated that smokers of these so-called “light” cigarettes, when compared to smokers of standard-tar cigarettes, tend to inhale more deeply and more frequently, and smoke more cigarettes per day, in order to maintain similar blood levels of nicotine throughout the day.  This new study from the Massachusetts Institute of Technology and the American Cancer Society looked at the incidence of lung cancer among smokers of medium-tar filtered and unfiltered cigarettes, and smokers of low-tar and very-low-tar filter cigarettes.  A total of 364,239 men and 576,535 women were enrolled in this prospective 6-year study. 

Not surprisingly, all cigarette smokers experienced a significantly greater risk of developing lung cancer than people who had previously quit smoking, or who had never smoked.  More importantly, all smokers of filtered cigarettes, irrespective of the tar content, experienced statistically equivalent risks of developing lung cancer.  Study participants who smoked high-tar unfiltered cigarettes experienced an even greater risk of developing lung cancer than those who smoked filtered cigarettes.  Among people who are familiar with the mechanisms of carcinogenesis and nicotine addiction, of course, these results are hardly surprising.  But the results of this very large-scale study add powerful scientific weight to the argument that there is no such thing as a “safe cigarette.”

There is a reasonable strong body of research linking Type A personality traits to an increased risk of heart disease and stroke.  However, little is known regarding the actual impact, if any, of chronic hostility on mortality due to coronary artery disease.  The current issue of the journal Circulation contains an interesting research study that looked at 259 men who died of coronary artery disease during the 16-year study, and 259 living patients who were carefully matched to the deceased patients in terms of their cardiovascular risk factors and demographic factors.  Both groups of patients had significant preexisting risk factors for cardiovascular disease.  All participants in this study were part of a larger research study, the Multiple Risk Factor Intervention Trial.  A standardized hostility assessment test was regularly administered to all study participants.

The study revealed that the men who scored highly on the hostility test had a 61% relative increased risk of death due to cardiovascular events when compared to men who had a low hostility index.  When the authors looked at the risk of death among the men who had experienced at least one non-fatal cardiovascular event during the course of the study, the highly hostile men experienced a five-fold increase (500% relative increase in risk) in the likelihood of subsequent death due to a cardiovascular event when compared to the “low-hostile” men.  The authors point out that stress and behavior modification may play an important role in reducing the risk of fatal heart attacks in men with hostile demeanors, and particularly in men with a history of prior non-fatal cardiovascular events.  Sounds like the basis of an important future study….

Dr. Robert A. Wascher