Friday, July 20, 2012

Hormone Replacement Therapy (HRT) another update, but does it matter

Dr. HR Nelson and her colleagues have updated the continuing data accumulation regarding HRT ,largely from the Women's Health Initiative, and can be found in the July 17 Annals of Internal Medicine.Menopausal Hormone therapy for the Primary Prevention of Chronic Conditions. Ann Int Med 17 July 2012:;157(2) 104-113.

The hope was ( back in the early 1990s) that menopause could be "treated" with female hormones; estrogen and progesterone in women with a uterus and estrogen alone for women who had a hysterectomy.Anticipated benefits would include relief of menopausal vasomotor symptoms ( this could legitimately be called treatment) and in addition various other beneficial effects would occur which would be considered preventive. This list included prevention of osteoporosis and even coronary artery disease and stoke plus preservation of vaginal tissue health and maybe even smooth skin.

Hot flashes are prevented by HRT but as far as the preventive aspects the results have been confusing, mixed and seemingly changing every time an update of data analysis is performed and may not apply at all or only tangentially to the early post menopausal woman.

Although it was hypothesized that HRT would decrease the risk of coronary artery disease data showed that the combination of estrogen and progesterone (combo treatment) increased the risk but now the revised data indicate that the earlier report of increased risk has to be revised because now the hazard ratio is no longer statically significant.HR =1.22 with range of 0.99 to 1.51. Estrogen alone had no effect on heart attack risk.

Since breast cancer is an estrogen hormone dependent there was initial concern that prolonged estrogen use would lead to an increase risk of breast cancer. However, the data upon reanalysis shows that estrogen alone actually decreased breast cancer risk while it is the combo therapy that increased breast cancer risk. The HR for combo therapy and breast cancer is 1.25 with a range from 1.07-1.46. The HR for estrogen alone is 0.77 (0.62--0.95)

Both combo and estrogen alone are associated with an increased HR for stroke, both about 1.35.


On a positive notes both the combo and estrogen alone were associated with a decreased HR for hip and vertebral fractures, with HR s in the 0.70 range.

So the latest analysis would suggest that both treatment regimens will decrease fracture risk and both increase the risk of stroke.Neither currently seems to change heart attack risk.Combo therapy increased risk of breast cancer while estrogen alone decreases it.

The really big caveat to all of this is that is might not really apply meaningfully to a discussion with a women beginning menopause. The discussion section of the article captured that thought with an understatement:

"The participants were generally aged 60 -69 years ,which restricts the applicability of our findings."

You wonder how applicable it is at all.

For the most part the elevated hazard ratios were less than 1.5 and I have blogged more than once about the significance or lack thereof of relative risks or hazard ratios less than 2 and will shamelessly quote myself again:

... great quote, from Michale Thun, VP of Epidemiology and Surveillance Research at the American Cancer society:

With epidemiology you can tell a little thing from a big thing.What's very hard to do is to tell a little thing from nothing at all.

Gary Taubes in his widely cited article,"Epidemiology Faces Its Limits",Science, Vol 269,p. 164,July 1995, followed that quote with this comment:

...journals today are full of studies suggesting that a little risk is not nothing at all.

So much of what we have is a collection of hazard ratios of less than 2 largely from studies involving women in an age group which now would not be considered candidates for HRT anyway.

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