What are sex hormones? The one most commonly discussed is estrogen. Actually, estrogen is the name of a family of hormones. The potent estrogen made by ovaries is estradiol. There is a far less potent estrogen, estrone, also made by the ovaries. Estrone has about 1/10th the potency of estradiol. There is also a natural estrogen made by the placenta of pregnancy, estriol, but estriol is not normally present in the non-pregnant woman. It apparently has no role in the non-pregnant state.
In addition to the natural estrogens, science has created synthetic estrogens for use in birth control pills. The most common of these is ethinyl estradiol. Basically, a chemical addition has been tacked on to the estradiol molecule to protect it from destruction by the intestine and liver.
Everything we swallow, which gets absorbed from the intestine goes to the liver. The liver processes all food and medication. In the process, most swallowed natural hormones are almost completely destroyed by the liver. If we give a high enough dose of a natural hormone, some escapes destruction and can provide the desired hormone effect. The problem we face is that high doses of estrogen in the liver also change liver physiology. One of the most critical changes induced by oral estrogen is the increased production of clotting factors, which can increase the risk of developing blood clots.
What is a bio-identical hormone? In the case of estrogen, it is estradiol. To be more specific, there is a specific configuration of the structure of the estradiol molecule which is biologically active. The configuration is referred to as estrdiol-17-β. Other configurations do not have much biologic activity. All estrdiol-17-β preparations are bio-identical to what the ovaries make. The body really does not care where the molecule came from, only that it is the right molecule in the right configuration. What may be significant is the route of administration of the hormone. Since route of administration is an issue for all hormones, let’s identify the others that may have an impact on mature women.
Estrogens are important for the health of all the soft tissues of a woman’s pelvis, as well as the preservation of bone mass. Estrogens actually decrease the rate at which bone calcium is lost. Estrogens also decrease the risk of blood vessel disease which can lead to heart attack and stroke. By the way, high estrogen levels usually make a woman feel good.
Another hormone made by the ovaries is progesterone. Progesterone is made after ovulation, so if a woman does not ovulate, she does not make progesterone. There are 2 important issues related to lack of ovulation and lack of progesterone. Obviously, if a woman does not ovulate, she will not become pregnant. The other is related to the fact that progesterone is a natural antagonist to estrogens. One of the things estrogens do is to stimulate growth of the uterine lining, endometrium. If estrogen stimulation of endometrial growth is not opposed, there is an increased risk of developing a cancer of the uterine lining. Women using estrogen replacement need to also use progesterone or a synthetic progestin, to protect their uterine linings, unless they have already had a hysterectomy. Progesterone, as a natural estrogen antagonist, has an effect beyond the uterus. Whereas estrogen generally improves a woman’s mood, progesterone frequently causes a depression of mood and mental activity.
The ovaries produce more than estrogens and progesterone. Ovaries make testosterone. Yes, that is the male hormone made in testicles. It is also made in ovaries. In fact, estradiol is made from testosterone. If the ovaries did not make testosterone, they could not make estradiol. Some investigators have data which imply that testosterone, as well as estrogens, may be mediators of libido, or sex drive. Some data indicate that women with low testosterone levels may have more energy and improved libido if they are provided with some testosterone supplementation. Since there seems to be some conversion of testosterone to estradiol in the brain, it is uncertain if it is actually testosterone, or estradiol which is the primary mediator of libido in women.
Estrogens, progesterone, and androgens (male hormones like testosterone) are all steroid hormones. They have the same basic skeletal configuration. DHEA, a pre-hormone for these very active hormones, has received a fair amount of attention in the popular literature. There are even a few studies which imply that there may be some significant biologic activity of DHEA. You might say that DHEA is a pre-steroid. All of the steroid hormones are made from DHEA after various chemical and structural changes. Unfortunately, not as much research has been performed related to the effects of DHEA, itself. One study from Monash University seems to indicate that the administration of DHEA to depressed women improved their recovery. Interestingly, DHEA production peaks at about the age of 30, and declines significantly, after that.
All of the hormones we have discussed are made by the ovaries. They are also made by the adrenal glands, but to a lesser extent. Just as we observe a decline in ovarian function with time, there also seems to be decreasing adrenal production of hormones. Actually, the adrenal glands are an important source of DHEA.
Another hormone which may need replacement is thyroid hormone. Thyroid hormone regulates the physiology of all the cells of the body. Low thyroid hormone levels can cause a person to have low energy levels and cause cold intolerance and fluid retention. Although low thyroid, itself, does not make someone fat, the decreased activity level associated with low thyroid hormone levels may lead to obesity.
There are a number of other hormones made by the body, but as a general rule, they do not decline much after the age of 40. Certainly it is possible to develop a form of diabetes related to low insulin levels, but that form of diabetes is generally identified in children. It is the steroid hormones which seem to be issues in the mature adults. Fortunately, we have hormones to provide supplementation or replacement, and various ways to deliver these hormones.
Almost everyone is aware of estrogen pills. One of the best known is Premarin®. Premarin is a mixture of estradiol, estrone and 2 estrogens made by horses, equilin and equilenin. Premarin is extracted from the urine of stallions. That’s right, male horses. Testicles make estrogens, just as ovaries make androgens. The only component of Premarin which provides any real benefit is the estradiol portion. Premarin is quite an old product, and, to my thinking, over priced. As an oral preparation, its first stop is the liver, where much of it is destroyed and it alters liver activity. Perhaps a better pill, and certainly cheaper, is a pure estradiol preparation. It actually is bio-identical to what a woman’s ovaries make. The other pill form of administering estrogen is the synthetic estrogen of birth control pills.
If we do not want to blast the liver with estrogen, there are alternate ways to administer the preparation. Years ago, a semi-synthetic estrogen was injected monthly as a depot of hormone. It was uncomfortable and required frequent returns to the physician. There are creams and gels, but they wash off, sweat off and swim off. They also can get deposited on other people by direct contact. It is probably undesirable for a pre-pubertal child to come in contact with much of the topical estrogen. There are also patches which deliver estradiol. They do work well, if they stay on. Also, the adhesive can cause local skin irritation for some women. Finally, estradiol can be fashioned into a pellet, which is inserted under the skin. It does need to be replaced every 3 to 4 months, as it is used up. The advantage is that there is no direct stimulation of the liver and no concern about maintaining the dosage. There is a constant, steady release of hormone for several months, and requires no further management other than replenishment after it is used up.
Progesterone can also be delivered in several ways. A semi-synthetic form of progesterone, Provera® is generally well tolerated. It seems to behave just like the natural hormone, even though it has been slightly modified to survive the intestine and liver. There is an oral progesterone preparation, Prometrium®. Unfortunately, the blood levels of progesterone after Prometrium ingestion vary widely and are quite unreliable. We still use daily intramuscular injections of progesterone in oil for our IVF patients. They don’t much like that. Since the real need for progesterone is to protect the endometrium, we really do not need a significant blood level, except to get the hormone to the uterine lining. Actually, progesterone is very well absorbed through the vagina, and vaginal administration provides excellent tissue levels in the endometrium, without providing a significant blood level. That decreases the problem of mood suppression related to high blood levels of progesterone. The down side is that vaginal progesterone, whether suppository, gel or capsule, is messy. The 2 commercial progesterone vaginal gels on the market are a bit expensive. Whereas progesterone vaginal capsules are not as much of a mess as the suppositories, they do produce a bit of discharge.
Testosterone treatments are available as injections, gels and pellets. The same discussion applies to administration of testosterone as does to estradiol. I am not aware of an oral testosterone preparation, but it would face the same fate as an oral estradiol pill.
DHEA is marketed over the counter at many pharmacies and in health food stores to consume orally. It is not likely to provide much benefit as an oral preparation. Some compounding pharmacists do provide a DHEA pellet, just like they do estradiol and testosterone.
Hormone replacement or supplementation can markedly improve the health and feeling of wellbeing for women. It is, however, important to determine which hormones need to be administered and to select the route of administration that best suits the needs of each patient. As noted, each has its advantages and drawbacks. Although nothing is perfect, it is usually possible to devise a treatment plan that satisfies the needs of each individual. We have a number of delivery systems available, and women have the opportunity to determine which ones they prefer.
My goal in providing hormone replacement or supplementation for patients is to try to restore their hormone levels to what they would be if my patient were about 30 years old. I think most women feel best at that age, and if I can help restore that sense of well being by recreating that kind of hormonal environment, I have improved quality of life.
Dr. Jacobs is a Reproductive Endocrinologist, practicing in Carrollton, Texas, a northern suburb of Dallas. He completed his residency training in obstetrics and gynecology at Baylor College of Medicine in Houston, and remained at that institution to become its first fellow once Baylor achieved accreditation for an advanced training program in Reproductive Endocrinology and Infertility. Dr. Jacobs has served on the faculty of several medical schools and was director of Reproductive Endocrinology at Texas Tech Health Science Center in Amarillo. Currently, in addition to his clinical activities caring for infertile patients and those with recurrent pregnancy loss, he is Chairman of the IVF committee at Baylor Medical Center in Carrollton.
Barry Jacobs, M.D., 4323 M. Josey Lane, Suite #201, Carrollton, TX 75010 www.texasfertility.com
Phone: 972-394-9590 Fax: 972-394-9597
Sharon LaMothe
Infertility Answers, Inc.
http://infertilityanswers.org/
LaMothe Services, LLC
http://lamotheservices.com/
*Please note: Sharon LaMothe is not a MD, is not an attorney nor does she hold a mental health degree. All advice given is solely the experienced opinion of Ms. LaMothe. If you have any medical, legal or psychological questions or concerns, please contact your own Doctor, Attorney or Mental Health Professional.
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