Hormone levels decline as we age. Bioidentical hormone therapy replenishes the hormones that your body needs to function optimally. The molecule of the bioidentical hormone is identical in structure to the hormones naturally found in the body, including estrogen, progesterone, testosterone, DHEA, and thyroid. We at Chadds Ford Wellness use bioidentical hormones instead of synthetic hormones. We will assess your individual needs and help you bring your hormone levels into an optimal, more youthful range.
Estrogen and progesterone are sex hormones essential for health and well-being. Not only are the absolute amounts of each hormone important, but also the ratio of progesterone to estrogen is equally important. The following is a discussion of these two important hormones.
The primary female sex hormones are the Estrogens, which are derived from steroid compounds. While present in the highest level in women during their reproductive years, estrogens are present in both men and women. Estrogens 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 may be cancer preventing. Estriol has most of it’s effect on the mucosa and maintaining moisture and lubrication.
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.
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. Perimenopause or Poly Cystic Ovararian Syndrome can also cause a relative estrogen dominance state.
Symptoms and diseases due to Estrogen Dominance can include:
These signs may indicate your estrogen status, including:
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 or a better term, bioidentical estrogen.
By far the most common estrogen replacement medication is Premarin®. The name “Premarin” actually comes from a “pregnant mare’s urine.” This means it’s “natural.” But it is not “bio-identical” to human estrogen. Premarin contains over 40 different xenoestrogens, plus E1 & E2. 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.
The problem with Estrogens that are not bioidentical are the side effects they posses. In a land mark trial called the World Health Initiative Trial (WHI) trial, researchers studied the effects of Premarin and Provera on 160,000 thousand nurses with an age range of 50-79 over a 15 year period. The study focused on the prevention of heart disease, cancer and osteoporosis. When used alone in women less than 10 years from the start of menopause, Estrogen decreased the risk of heart disease, which is a good thing. However when combined with Medroxyprogesterone Acetate or Provera (a non-bioidentical type of progestin), the risk of heart disease went up. The risk of heart disease also increased in women who started HRT more than 10 years after starting menopause (even without the dangerous progestin, Provera). We now know when prescribing HRT to our female patients, we must use bioidentical estradiol and progesterone. Newer studies have shown a reduced risk of coronary artery disease when using Estrogen orally, (especially when started before the 10th year after menopause and low cardiac risk factors, non-smokers) combined with an adequate dose of Progesterone.
Our preferred method of administering ERT is by way of an oral estradiol pill (E2). This is due to it’s added cardio-protective effects after being metabolized in the liver. Oral estrogen is preferred over topically delivered estrogen if the woman being treated is less than 10 years from beginning menopause and her risk of developing heart disease is low. Using a custom compounded Estradiol cream is also very good, but not as good as the pill due to the reason’s above. Creams get absorbed directly into the blood stream through the skin, avoiding breakdown in the stomach and liver.
When you ask your primary care physician or OB/GYN physician about the difference between Hormone Replacement Therapy (HRT) and Bio-identical Hormone Replacement Therapy (BHRT), they may say there is no difference! Estrogen and Progesterone are all the same! They will also quote organizations such as ACOG (the American College of Obstetrics and Gynecology) as stating the same thing. They will say that long-term use of Estrogen and Progesterone can cause heart attacks, strokes, and breast cancer. In fact when treating symptoms of menopause, your doctor is trained to only use HRT at the lowest dose, for the shortest period of time necessary to control your symptoms and then discontinue the medication for fear that it will harm you. In contrast we are certified by the World Link Medical Organization and we have been trained by masters of the Age Management Medical Literature that have looked at all of the available evidence on the safety and efficacy of HRT versus BHRT. The evidence clearly shows that HRT is not equal to BHRT. The side effects and health effects of the progestins and unopposed estrogen is dangerous to our patients. On the other hand, when prescribed by well trained practioners, who follow up regularly with their patients and follow their lab levels, BHRT can be done safely and effectively to help our patients feel better, look better, prevent diseases of aging and avoid long term complications and diseases of aging, such as heart disease, diabetes, stroke, breast cancer, Alzheimer’s disease and osteoporosis among many others.
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 pregnancy 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 peri or postmenopausal women.
Progesterone has a number of physiological effects, usually to counteract the effects caused by estrogen. The effects and benefits of progesterone include:
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 that may protect against developing breast cancer.
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 the 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 such as the Yam. Synthetic progestins are not human progesterone, and they will not cause many of the favorable actions of endogenous or bio-identical progesterone. As a matter of fact the different chemical side chain molecules on the chemically different progestins are believed to cause many harmful diseases and side effects not seen with bioidentical 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 prevent the production of the protective P53 gene, thereby losing the protective effect against cancer cell formation. 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. But, unopposed estrogen also increases the risk of breast and uterine cancer and estrogen should never be prescribed without progesterone.
Following the discussion, the preferred method is to use bio-identical progesterone replacement. But progesterone is poorly absorbed by oral ingestion unless micronized. “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 clinicians prescribe progesterone as a cream to be applied to the skin of the forearm. Unfortunately adsorption through the skin is only 1/4th of that of through the mucous membrane or the gut so the preferred method is by sublingual through a troche or by mouth in a pill form. If our patients suffer from insomnia, progesterone by mouth can kill two birds with one stone! A very important point for those women who are prescribed topical progesterone and estrogen is to realize since progesterone is adsorbed so poorly through the skin you are not attaining adequate healthy blood levels that will counteract the harmful effects of unopposed estrogen and you can end up with an increased risk of breast and uterine cancer as well as symptoms of estrogen dominance! If your doctor is prescribing topical hormones for you and checking saliva tests to confirm good adsorption there’s a problem with that practice. Saliva testing gives a decent picture of hormone levels before medications are applied topically, but once they’re applied to the skin the hormones saturate the skin as an organ including the saliva glands and do not correlate with blood levels. To prove this fact, ask your doctor to check blood levels at the same time as saliva levels and see if this is true for you as well. You can get an adequate blood level with topical progesterone, but it would take 4X the amount most doctors prescribe, which is too costly and messy.
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 considerably lower value than that which is available from products available from compounding pharmacies. In other words, don’t waste your money! Insurance companies are not covering compounded medications like they used to. There is one way that progesterone is usually covered and that is with a generic progesterone pill called Prometrium. Again, this is a great solution for a woman who suffers from insomnia. In order to get adequate blood levels we need to usually give two times the dose as we would need to give for someone on a sublingual form of progesterone, which is the best way to absorb the hormone.
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 100mg to 200mg total a day, either once or twice daily. Dosing is adjusted based on changes in symptoms and by following lab values (blood levels).
Peri-Menopause and Menopause
Progesterone levels are usually the first to decline as a woman ages and enters peri-menopause. 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 simply 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.
A word on surgically applied hormone pellets. They are an acceptable form of hormone supplementation. However, we do not use them for a couple reasons. It's a surgical procedure that leaves a small scar when they are inserted 2-3 times a year. If the dose of any of the hormones in the pellet are off you either deal with the symptoms and side effects until the next pellet insertion, surgically remove it and try again with a new pellet or add a pill or cream to supplement until the next pellet is due. I believe it makes more sense to use creams, pills and sublingual hormones until the hormone levels are titrated to your optimal clinical effect and your blood levels are in the optimal safe zone and then a pellet might make sense.
Please see the Controversy section above under Estrogen. Your doctor will have the same reaction with progesterone replacement as estrogen. Also, many practioners that are practicing BHRT will advise you to use topical progesterone at too low a dose and follow your labs with saliva testing. This will leave you with too low of blood levels of progesterone and will in effect be giving you an unbalanced prescription of estrogen to progesterone. This is the same thing and gives you the risk of unopposed estrogen, namely estrogen dominance effects and increases the risk of female cancers. One other controversy should you cycle your hormones or do them continuously. If you are in menopause there is a faction of doctors and women who think it is natural and healthy to cycle the hormones so you go back to having your monthly period. That is fine under the old adage ‘to each there own’. but I want to say there is no medical reason to do this form of replacement. As a matter of fact, if the hormones are helping us age better, feel better, look better and reduce the risk of age related diseases, why would you want to eliminate the very hormones that are responsible for these optimal effects for 25% of the month that you are off of them when you are having your menses? Again, this is a personal decision. I am fine with it as long as my patients have all the information to make an informed decision on the chosen treatment strategy.
For more information on compounding, go to:
International Academy of Compounding Pharmacists
Professional Compounding Centers of America
Portions of the information above used with permission form Dr. Paul Tortland’s website jocdoctors.com