Estrogen Therapy

The greater part of any discussion regarding menopause should be dedicated to the role of estrogen in the maintenance of female health. Estrogen plays a greater and more wide-range role in hormonal physiology than progesterone with the bulk of literature regarding progesterone’s role in menopausal therapy as a balance for any potential pro-proliferative effects of estrogen on uterine tissue. There will be some data presented regarding other potential benefits of natural progesterone replacement, but we will start with estrogen.

Classic texts cite estrogen production as being 60% from ovarian tissue and 40% from adipose tissue. These proportions are probably not accurate since estrogen levels can fall from peaks of greater than 700 pg/ml or an average of 100 pg/ml before menopause to near zero afterward. At age 60, an average unsupplemented female will have lower estrogen levels than a similarly aged man.

menopausePhysiologic effects of estrogens include maintenance of uterine and breast tissue, significant effects on vaginal mucosal thickness and lubrication; aiding in maintaining proper vaginal flora. Additionally, estrogen is associated with quality retention of the distal urinary tract. Local vaginal and systemic effects play an important role in libido and aiding sexual function.

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The presence of estrogen is also associated with more advantageous cardiac valve and blood vessel elasticity with notable declines seen after menopause. Maintenance of estrogen is also associated with better lymphocyte function, maintaining lipid profiles and the continued expression of steroid receptors.

Newer studies have demonstrated estrogen’s beneficial effects on cortical function, as demonstrated on PET scans. A negative correlation exists between estrogen levels and risk for Alzheimer’s disease. In addition, maintained estrogen levels have a strong correlation with significant reductions in risk for colon cancer and macular degeneration.

The presence of estrogen is associated with improved glucose metabolism in all spheres: better insulin sensitivity, decreased lability of glucose levels, improved insulin kinetics and lower HBA1C levels. These benefits also are demonstrated by the association of estrogen levels and decreased central adiposity.  Other studies have shown the correlation between estrogen levels and sleep quality, and skin elasticity retention and thickness of the dermal basal layer.

Estrogen replacement has been shown to improve mood scores in depressed subjects. The influence of estrogen and retention of bone mineral density is well described.

While the benefits of estrogen maintenance have been mentioned previously, there are several health considerations regarding estrogen hormone replacement therapy (HRT), which must be taken into account when deciding whether or not to undertake therapy or how long to continue it.

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The following discussion will focus on risk/benefit aspects of estrogen HRT with regard to prevention of coronary artery disease, osteoporosis, cognitive decline and associated risk for uterine cancer, breast cancer and venous thrombosis. Also the choice between synthetic and bioidentical hormones will be discussed. Additionally, the route of hormonal delivery is of critical importance with some forms demonstrating clear-cut adverse effects.

Any discussion of the risks versus benefits of HRT must first be put in perspective. The vast majority of the studies to date (including those cited in this material) were performed on oral conjugated equine estrogens and synthetic progestins. CEE contains forms of biologically active estrogens, which are not natural to humans. In addition, the oral forms (discussed later) have been shown to increase CRP, a biomarker of inflammation. Studies continue to mount, linking inflammation to increased heart disease and stroke risk, cancer and even Alzheimer’s disease. The oral delivery route can also decrease IGF-1 levels as well.


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