About EstrogenEstrogen refers both to natural estrogen hormones in the body and estrogen products used in medications. The main forms of estrogen found in women's bodies—endogenous estrogen—are:
- estradiol, the main estrogen made by women’s ovaries before menopause (also described as 17-beta estradiol and E2)
- estrone, a weaker estrogen produced both in the ovaries and in fat tissue from other hormones, and the main estrogen found in women after menopause (E1)
- estriol, the weakest of the three main forms of estrogen, made in the body from other estrogens (E3).
The amount of these estrogens in the body varies over the course of the menstrual cycle. After menopause, estrone becomes the predominant endogenous estrogen in women’s bodies even though the ovaries continue to produce small amounts of estradiol, as do the secondary hormone-production sites. The adrenal gland continues to produce androstenedione, which is converted to estrone and estradiol in body fat and in muscle and skin cells. In addition, the ovaries continue making small amounts of testosterone, which can be converted to estradiol.
How does estrogen function in the body?Estrogens, particularly estradiol, are powerful female hormones that make a girl develop into a woman capable of reproduction. Whether from your own ovaries or from an external source, estrogens work in the body by traveling in the blood to body tissues where there are estrogen receptors. Estrogen receptors are found in the brain, breasts, heart, blood vessels, uterus, vagina, bladder, liver, bones, skin, and gastrointestinal tract. Estrogen molecules bind, or attach, to estrogen receptors much like a key fits into a lock, and this leads to effects that vary from one body part to another. Not all parts of the body have estrogen receptors, and not all estrogen receptors are alike. Estrogen receptors in bone tissue are not the same as estrogen receptors in breast tissue, for example. There are other factors that influence the differing effects of estrogen in different parts of the body, but not a great deal is known about these other factors.
What are the effects of lower estrogen levels?Because estrogens have important effects on so many body tissues, it is not surprising that when a woman’s estrogen levels drop (especially when they drop suddenly), there may be negative or potentially negative effects. One of the most noticeable effects, of course, is the end of menses, the monthly periods. The end of menses is due in part to estrogen levels that are too low to stimulate the lining of the uterus (endometrium). In addition to the end of menses, significant estrogen loss can also lead to:
- hot flashes and night sweats with disturbed sleep
- vaginal dryness and loss of elasticity of vaginal tissue
- increased urinary tract infections and problems with urinary incontinence (difficulty holding one’s urine)—although childbirth appears to be the most important cause of incontinence in postmenopausal women
- loss of sexual desire and function
- changes in mood, or depression
- memory problems and possible increased risk of Alzheimer’s disease
- breast changes—loss of firmness
- skin changes—thinner skin, less collagen and moisture in the skin
- loss of bone density—may eventually lead to osteoporosis
- increase in cholesterol levels—may increase risk for heart disease
- loss of numerous beneficial effects of estrogen on body organs and systems.
Estrogens used in ERT, HRT and NHRTEstrogen products may provide either a single type of estrogen or mixed estrogens. The most commonly prescribed form of estrogen for HRT in the U.S. for many years has been a mixture of estrogens extracted from the urine of pregnant mares (Premarin, and the estrogen in Prempro and other estrogen products that begin with Prem-). Prempro is the combined estrogen/progestin formulation that was recently found in the WHI study to be associated with a somewhat increased risk of breast cancer, heart attack, stroke, and blot clots.
There are many alternatives to Premarin available to women today. Other estrogen products, including bio-identical estrogens, are made in the laboratory from plant materials. Estrogens can be taken in pill form or as sublingual (under the tongue) tablets. There are also estradiol skin patches (transdermal estrogen), and some estrogen products can be used in the vagina. An estradiol skin gel (Estrogel) is available in many countries including Canada, but is not yet available in the U.S. An estrogen nasal spray is being tested. Most estrogen products delivered through the skin are bio-identical estrogens, but some oral and vaginal estrogens are not (e.g., Premarin, Ogen, Cenestin, Premarin vaginal cream). The estrogen used in transdermal patches is bio-identical estrogen (estradiol); however, the estrogen used in the new contraceptive skin patch (Ortho Evra) is a synthetic estrogen.
Estriol is not often used in HRT, although it is possible to have an estrogen cream that contains estriol made to order by a compounding pharmacy. Estriol, while much weaker than estradiol, is still able to cause systemic effects on the user, and studies have found that oral estriol can stimulate the endometrium. Vaginal estrogens are less likely to cause systemic effects and are quite effective for restoring vaginal and urogenital tissues to premenopausal conditions and reducing urinary tract infections. Different products may have somewhat different effects and side effects. Oral estrogens seem to have more side effects than estrogens delivered through the skin or the vagina, apparently due to the "first pass" through the liver that occurs when drugs are taken by mouth. Lower doses of estrogens generally have fewer side effects than higher doses and may be effective for treating symptoms of menopause.
The differences between oral and transdermal estrogensOral estrogens are quickly broken down by the liver, and this "first pass" through the liver seems to be responsible for certain side effects as well as for the positive effects of oral estrogen on cholesterol levels, lowering LDL (the "bad" cholesterol) and raising HDL (the "good" cholesterol). Oral estrogen sometimes raises triglycerides (another type of blood fat) and women who have high triglyceride levels should be aware of this. Transdermal estrogen does not raise HDL and usually does not lower LDL cholesterol as much as oral estrogen, and it does not affect triglycerides, so it may be a better choice in women with elevated triglyceride levels. Avoiding the first pass through the liver also may prevent the increased risk of blood clots and gallbladder problems associated with oral estrogens.
UPDATE: Results of a study reported in the Journal of the American College of Cardiology (April 2003) show that Premarin pills, a form of oral estrogen, increase C-reactive protein (CRP) in the blood, while Climara, an estrogen skin patch, does not. CRP is a marker of inflammation in the blood that has been found to be a heart disease risk factor. The study confirms earlier research showing that transdermal estrogen does not raise CRP levels in the blood, while estrogen pills do Vehkavaara S et al., 2001).
Transdermal estrogen and oral estrogen have differing effects on androgens in the body. Oral estrogen lowers free testosterone and can lead to androgen deficiency (affecting libido among other things), while transdermal estrogen has little effect on testosterone levels. Transdermal estrogen may offer other advantages over oral estrogens, although more research is needed.