Estrogen and progesterone are essential hormones for health and well-being. Not only are the absolute amounts of each hormone important, but also the ratio of progesterone to estrogen is just as critical. Following is a discussion of estrogen and progesterone.
Estrogens are a group of steroid compounds functioning as the primary female sex hormone. While estrogens are present in both men and women, they are usually present at significantly higher levels in women of reproductive age. They promote the development of female secondary sex characteristics, such as breasts, and are also involved in the thickening of the endometrium of the uterus and other aspects of regulating the menstrual cycle. Follicle stimulating hormone (FSH) and luteinizing hormone (LH) regulate the production of estrogen in ovulating women.
The three major naturally occurring estrogens in women are estrone (E1), estradiol (E2), and estriol (E3). In the body these are all produced from androgens through enzyme action. Estradiol is produced from testosterone, and estrone is made from androstenedione. Estrone is weaker than estradiol, and in post-menopausal women more estrone is present than estradiol. Estrone may be cancer-inducing. Estradiol is the most potent estrogen. And Estriol may be cancer protective.
Estrogen is produced primarily by developing follicles in the ovaries, the corpus luteum and the placenta. Some estrogens are also produced in smaller amounts by other tissues such as liver, adrenal glands and the breasts. These secondary sources of estrogen are especially important in post-menopausal women.
Estrogens are also common in our environment. Animals raised for commercial food purposes often are fed hormones containing estrogen to speed their development and time to market, and to enhance taste and marketable characteristics. Pesticides often contain hormones and work by disrupting the insects’ normal hormone cycle. Foods sprayed with pesticides may absorb some of the estrogen-like compounds. A class of estrogen-like substances called phthalates are part of the formulation of many plastics. Heating foods in plastic containers may allow some of these phthalates to leach out into your food. These estrogens and estrogen-like compounds are known as xenoestrogens (ZEE-no-estrogens). “Xeno-“ means “foreign.” These estrogens are not human estrogens, and are therefore foreign to our bodies. Yet when absorbed in our bodies they can exert estrogen-like effects.
Estrogen has many benefits. These include:
- Preventing of heart disease
- Stroke prevention
- Osteoporosis prevention
- Decreased Alzheimer’s risk
- Preventing urogenital atrophy
- Preventing macular degeneration
- Reducing menopause symptoms such as hot flashes, depression, and mood swings
- Reducing memory loss
- Reducing tooth loss
- Reducing colon cancer
- Estrogen Deficiency
Low levels of estrogen, or estrogen deficiency can cause many symptoms, including:
- Vaginal atrophy
- Skin dryness
- Thin bones, painful fractures
- Temperature dysregulation (feeling unusually hot, cold, or temperature swings)
- Breast changes
- Decreased libido
- Loss of anti-aging effects
- Vasomotor symptoms– flushing, hot flashes
- Increased risk of cardiovascular disease
- Increased risk of osteoporosis
- Increased vaginal dryness and urinary incontinence
- In men, estrogen blocks testosterone receptor sites, causing symptoms that reflect low testosterone levels
- There is also some research that suggests a possible link between low estrogen levels and increased risk of cognitive dysfunction and dementia.
In addition, as noted above, some researchers maintain that most women in the U.S. are estrogen dominant, due to high environmental estrogen exposure (the xenoestrogens). However, lab tests for estrogens typically do not reflect this increased estrogen exposure. Symptoms can include:
- Fibrocystic breast disease
- Weight gain, especially at the hips and thighs (estrogens are fat storage hormones)
- PMS, mood swings, depression
- Carbohydrate craving
- Water retention
Some simple tests that may indicate your estrogen status include:
- Breasts. If they are swollen or tender, your estrogen level may be too high. If there is a loss of breast fullness or if they are drooping, you may have too little estrogen.
- Fluid retention. If your rings are too tight, your estrogen level may be too high.
- Sleep. If you suffer from night sweats your estrogen level may be too low.
Estrogen Replacement Therapy
The most common hormone replacement therapy in use today is actually just Estrogen replacement. (It really should be called “ERT” not “HRT.”) Actually, estrogen replacement therapy is the most well-documented anti-aging therapy in the medical literature. The problem is the drugs used as estrogen replacement. None of the commercial products contain natural human estrogen.
By far the most common estrogen replacement medication is Premarin®. The name “Premarin” actually comes from “pregnant mare urine.” Yes, that’s right—horse urine! (That also means it’s “natural.” But it is not “bio-identical” to human estrogen.) Premarin contains over 40 different xenoestrogens, plus E1 & E2. Frighteningly, it also contains Equillin, a horse estrogen and a known breast carcinogen. No wonder there has been a growing concern over the adverse effects of its use! Prempro® is a mixture of the same conjugated estrogens found in Premarin and medroxyprogesterone.
Our preferred method of administering ERT is by way of custom-formulated topical creams containing bio-identical estrogens, most commonly Estradiol (E2) and Estriol (E3). Creams get absorbed directly into the blood stream through the skin, avoiding the problem of breakdown in the stomach and liver. (See
One common commercially available cream is Bi-Est®. Bi-Est (“Bi-” meaning “two,” and “-Est” meaning “estrogen”) contains a mixture of 20% E2 and 80% E3. It is also available as an oral capsule.
Converting From Commercial Estrogen to Bio-Identical Estrogen.
If patient is on Premarin 0.625mg or Estrace 0.5mg or Estraderm 0.05mg or Estinyl 0.02mg or Ogen 1.25mg – switch to Bi-Est 80/20 at 2.5mg per day (oral or topical)
If patient in on Prempro – switch to Bi-Est 80/20 at 5mg plus Progesterone 50 to 200mg per day (oral or topical)
If patient is on Estratest – switch to Bi-Est 80/20 at 2.5mg plus Testosterone 2.5mg per day (oral or topical)
Progesterone is a steroid hormone involved in the female menstrual cycle, pregnancy, and human fetal development. Progesterone belongs to a class of hormones called progestagens, and progesterone is the major naturally occurring human progestagen. Progesterone should not be confused with progestins, which are synthetically produced progestagens, such as in Provera.
Progesterone, like all other steroid hormones, is synthesized from pregnenolone, a derivative of cholesterol (yes, cholesterol is a steroid hormone!). Progesterone is a precursor of other hormones such as cortisol and androstenedione. Androstenedione can subsequently be converted to testosterone and the estrogens estrone and estradiol.
Progesterone is produced in the adrenal glands, the ovaries, the brain, and—during pregnancy—in the placenta. In humans, increasing amounts of progesterone are produced during pregnancy, initially in the ovary, but after the 8th week of pregnancy production of progesterone shifts to the placenta. The placenta utilizes maternal cholesterol as the initial substrate, and most of the produced progesterone enters the maternal circulation, but some is picked up by the fetal circulation and is used as substrate for fetal hormones. At term, the placenta produces about 250-400 mg progesterone/day. One of the reasons pregnant women often feel so much better is the high circulating levels of progesterone!
Progesterone levels are low in children, men, and postmenopausal women.
Progesterone has a number of physiological effects, usually to counteract the effects caused by estrogen. The effects and benefits of progesterone include:
- Increases breakdown of fat
- Protects against endometrial cancer
- It is a natural diuretic
- It is a natural anti-depressant
- It exerts a calming, anti-anxiety effect
- Increases libido (sex drive)
- Helps prevent osteoporosis (when combined with estrogen)
- Decreases PMS Symptoms
- Decreases carbohydrate cravings
Progesterone plays an important role in brain function and is often called the “feel good hormone” because of its mood enhancing and antidepressant effects. Optimum levels of progesterone can promote feelings of calm and well being, while low levels of progesterone can induce feelings of anxiety, irritability and even anger.
Let’s look at some of these in more detail.
Effects on bone metabolism
Progesterone influences or regulates certain proteins in bone-forming cells. This assists in bone formation. In addition, Progesterone binds to certain hormone receptors, thereby helping prevent bone loss caused by naturally-occurring steroid hormones.
Effects on breast CA
Progesterone reduces breast cancer risk by inducing cell death in T47-D cancer cells. In addition, Progesterone increases production of the protective P53 enzyme.
Effects on the Brain
Progesterone is synthesized by Schwann cells, the cells that form the protective myelin coating around many nerve fibers. This enhances myelin formation in peripheral nerves and repair of the myelin sheath around the nerves in the brain. Furthermore, Progesterone affects expression of several brain proteins. These factors have implications for maintenance of nerve function in menopause and aging, and protection against neurodegenerative diseases, such as Alzheimer’s. The use of progesterone is also being heavily investigated for use in Multiple Sclerosis, because of its benefits on myelin formation and nerve protection.
Effects on the Cardiovascular System
Progesterone protects against atherosclerosis (hardening of the arteries) by preventing multiplication and migration of smooth muscle cells, which are involved in arterial plaque formation. Progesterone also reduces platelet aggregation (a key component of blood clots and cause of heart attacks and stroke) through the effects of nitric oxide, a naturally-occurring chemical that causes relaxation of the smooth muscle lining of the blood vessels.
While all progesterones are considered progestins, not all progestins are progesterones. There is only one real progesterone; it is produced by the human body or in a laboratory from plant hormones. Synthetic progestins are not human progesterone, and they cannot be substituted for many of the favorable actions of endogenous or bio-identical progesterone. For example, synthetic progestins (Provera®, norethindrone) bind to the natural Progesterone receptor sites and inhibit the action of natural Progesterone. In addition, unlike natural Progesterone, synthetic progestins do not produce the protective P53 gene, thereby preventing production of endogenous Progesterone. Furthermore, proliferation of breast epithelial cells (increasing the risk of cancer) is greater when synthetic progestins are combined with estrogen, when compared either to estrogen alone or no hormone replacement at all.
Following the discussion, the preferred method is to use bio-identical progesterone replacement. But progesterone is poorly absorbed by oral ingestion unless micronized and mixed in oil or with fatty foods; it does not dissolve in water. “Micronized” means that it is milled to a very small particle size to allow the progesterone to pass into cells and distribute throughout the body. Progesterone, and other bio-identical hormones, also can be custom formulated into creams, gels, lotions, tablets, liquids, suppositories, sublingual (under the tongue) tablets, and troches (medication on a stick that dissolves in the mouth).
Many “natural progesterone” products are heavily marketed to consumers, often said to contain extract of yams, with extensive claims and without need of prescription. Many contain fillers and unknown products. If they actually do contain any real progesterone, they are not likely to have U.S.P. quality, and the strength is always of considerable lower value than that which is available from products available from compounding pharmacies. In other words, don’t waste your money!
For menstruating women, progesterone is typically administered in cycles, most commonly on days 14-21 or 14-25 of the menstrual cycle. Post-menopausal women, or women who have had total hysterectomies may receive continuous daily progesterone, since there is not need for withdrawal bleeding.
Normal doses for natural progesterone range from 50mg to 200mg total a day, either once or twice daily. Dosing is adjusted based on changes in symptoms and by following lab values (blood or saliva testing).
Peri-Menopause and Menopause
Progesterone levels are usually the first to decline. Menopausal symptoms generally are related to Estrogen and Progesterone deficiency. Indirect effects include hot flashes, insomnia, and irritability. Primary Estrogen deficiency symptoms include vaginal dryness, painful urination, painful intercourse, and loss of menstruation. Secondary symptoms of Estrogen deficiency include dry skin, sagging breasts, osteoporosis, cardiovascular disease, and increased risk of Alzheimer’s Disease.
Bio-Identical Hormones and Compounding Pharmacies
Most commonly, bio-identical hormones are obtained by physician prescription from a “compounding pharmacy”. These are special pharmacies that can create unique or special-order medications, using U.S.P. certified and standardized medical grade ingredients. (“USP” stands for U.S. Pharmacopeia, and is your assurance of quality and standardization.) Typical chain-store pharmacies, such as CVS, Walgreen’s, Brooks, WalMart, etc., are dispensing pharmacies. They simple dispense commercial medications. They do not have the capability to compound or custom-formulate medications.
One of the benefits of custom compounding is the ability to combine multiple hormones in one cream or product, making application much more convenient. However, some physicians choose to use individual products initially until a final optimum dose of each supplement is determined. Then a combined product may be used.