Early use of estrogen has benefits, and few risks

The early estrogen prevention study: Kronos

The KEEPS study was done to understand the benefit of estrogen given to women at the beginning of menopause, rather than later, as was the case in the Women’s Health Initiative. The purpose of the study was to see if giving estrogen, either ora; conjugated equine estrogen, (Premarin), or transdermal bioidentical estrogen would decrease the risk of atherosclerotic changes in the coronary arteries. The study was double-blinded and placebo controlled. The progesterone given was micronized bio-identical progesterone, give 12 days per month. 

The study was conducted for four years. Women who were enrolled were within 3 years of their last menstrual period. This is typical of the patient seen in the office who seeks advice about menopausal symptoms and hormone replacement.

Women who had coronary artery calcium scores of >50 were excluded from the study. Women at high risk for heart disease, including obesity, diabetes, untreated hypertension, elevated lipids and those on statins, were also excluded. 

After the four years, there did not appear to be any difference in the thickness of the coronary arteries endothelium (the inner layer of the vessel) in any of the groups studied , but there was a trend toward less calcium developing in the coronary arteries. 

There were no cases of venous thromboembolism or blood clots in the study. They did find that improvements were noted in hot flashes, sleep, and bone density in both the oral and transdermal products. Sexual function improved with the transdermal product.  Depression and anxiety improved with the oral product. Neither product improved wrinkles, cognition, or breast pain. 

MRI’s of the brain were done on study participants and there was found to be in increase in ventricular volume, without a significant change in cognitive functioning. 

Estrogen deficiency affects both the physical and psychological changes related to sexual function. Decreased thickness of the skin of the vulva and vagina, decreased blood flow to the muscles, and loss of subcutaneous fat change the architecture and the function of the vulva. Estrogen also affects serotonin in the brain, which can influence mood and desire. Loss of estrogen in related to decreases in  mood, cognition, sleep and desire. 

Some of the women in the study agreed to participate in a study of sexual function, which evaluated desire, arousal, orgasm, lubrication, satisfaction, and pain. Both the transdermal and oral estrogen improved dryness and decreased pain, but the transdermal estrogen was better at improving the more subjective symptoms of desire, arousal and orgasm. The fact that sexual function is better with the transdermal estrogen may be an effect of increased free testosterone with transdermal vs. oral preparations. 

Estrogen affects the skin through a mechanism of collagen production and  hydration. Studies have show less wrinkling in women who have used hormones long term. Smoking increased wrinkling. In this short study, no difference was seen in any of the trial arms. 

As expected in this study, both types of estrogen preserved bone. 

As for breast health, neither of the hormone groups experienced more breast pain or cancer than placebo. 

When considering metabolism, the oral estrogen demonstrated a decrease in LDL, with in increase in HDL, total cholesterol, and triglycerides. The transdermal estrogen had more moderate results with no increase in triglycerides. Insulin resistance decreased which is significant for less cases of new onset diabetes in both groups. BMI increases were seen in the placebo groups, but not in the hormone groups, indicating that HRT does not cause weight gain. 

This study also looked at genetic variations in response to estrogen and how it affects cellular function.

In conclusion, the KEEPS study did not show harm when related to cardiovascular health, blood clots, and breast cancer in the first four years of hormone replacement if used within the first 3 years of the last menstrual period. It did show improvements in hot flashes, sleep and sexual function and bone health. 

2019-11-02 06:29:00


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