What about HORMONES?
What’s the story with all the buzz on hormones?

What are hormones, and do I have a deficiency? What about bioidentical hormones?
What is HRC? What is saliva testing? What are natural hormones? Are hormones safe?

I sure spend a lot of time answering questions about hormones. Let’s see if I can answer some of the questions without getting too complex or oversimplifying. First I should start by explaining that hormones are very powerful molecules made in various parts of our bodies to affect other parts of the body. They are commonly released into the bloodstream and react with receptors in certain other parts of the body. We could not live and function normally without hormones. Many hormones are made by glands, such as the thyroid gland, pituitary gland, and the adrenal gland. Hormones are also secreted by multiple other functional organs such as various parts of the brain, gastrointestinal tract, kidney, skin, heart, fat cells and genital organs. We all had hormones made by our placenta before we were born!

The hormones which concern my patients the most are those made by the ovary – estrogen, progesterone, and testosterone.

Estrogen is the primary female hormone, made mostly by the ovary, but to a small degree by fat cells. When young girls go through puberty, rising estrogen levels lead to breast development and menstrual flow. There then ensues a truly remarkable symphony of hormonal regulation between portions of the brain and the ovaries and the uterus which seems to be designed for the best chance of propagation of our species (pregnancy.)

Estrogen levels are low (<50) during menstrual flow and begin to rise and spike (>300) just before ovulation. Estrogen levels drop at ovulation and then rise again after ovulation. Estrogen causes the lining of the uterus (the endometrium) to grow thicker (proliferate.) If pregnancy occurs, estrogen levels stay up. If not, levels drop. There are many parts of the woman’s body which are affected by estrogen – estrogen receptors are found in many of a woman’s tissues. We know that bones depend on estrogen to maintain normal mineralization, the breasts need estrogen for development and function and maintenance of anatomic integrity, the vagina depends on estrogen for normal elasticity and secretions, the brain seems to need estrogen for thermoregulatory (hot/cold) stability, and sometimes estrogen seems to affect mood and generalized sense of well-being. These functions may be just the tip of the iceberg! There may be numerous effects related to estrogen which are subtle or variable among different individuals. Other disease states may be impacted by differing levels of estrogen.

Progesterone is the other hormone specific to females. It is produced by one of the ovaries once ovulation (passing an egg out of the ovary) occurs. The walls of the little cyst (follicle) which pops when the egg leaves the ovary become the yellowish corpus luteum (yellow body), which makes progesterone for that cycle or for the first part of pregnancy.

Progesterone levels are very low (<1) before ovulation but rise (usually >10) after ovulation. Progesterone causes the thickening endometrium layer to be more stable and prepared to accept pregnancy implantation. If pregnancy occurs, progesterone made by the corpus luteum of the ovary is essential to support the early pregnancy. If pregnancy does not occur, progesterone levels fall. It is the drop in both estrogen and progesterone levels which causes the endometrium to slough off, giving what is the normal menstrual (hormone withdrawal) bleeding. This paves the way for this lining of the uterus to begin to get ready for another chance at conception next month, with a new, freshly prepared, lush endometrial layer. So you see, just as the lining of the uterus is undergoing dynamic changes throughout the menstrual cycle, so are the female hormone levels changing.

This fact gives rise to the great confusion about hormone levels. Many women get told by their family doctors or family members that their various ailments are “hormonal,” and they come to their gynecologist to “get hormone levels checked.” These ailments can vary from undesirable mood changes, to headache, weight gain, loss of energy, and sexual dysfunction. Patients come seeking the answer to their problems in a pill, or fall prey to advertising leading to exotic and expensive and unreliable and dangerous pharmacologic remedies. More on this to follow.

So when does a patient need “more hormones?” Well first we need to talk about menopause. Menopause is the day the ovaries stop working. The time before menopause is called PREmenopause, and the time after is called POSTmenopause. The time around all this change, when the ovaries may be dysfunctional or intermittently working, is called the PERImenopause, which might be measured in months or even years. Sometimes it is difficult to tell exactly where a woman is in this journey – that is an appropriate time to draw “hormone levels.” I am interested in estrogen levels, but as we now know, estrogen levels go up and down during the normal menstrual cycle. If I draw a single estrogen level, I might be fooled, so I also draw another hormone level called FSH (follicular stimulating hormone.) FSH made by the pituitary gland of the brain. FSH levels go up when estrogen levels go down, so if my blood test shows low estrogen and high FSH, I can be pretty certain that the ovaries are not working very well, and menopause is imminent or past. AMH (anti-mullerian hormone) is another hormone which changes (goes down) with menopause and may be a helpful lab test. By the way, as far as I can tell, the only reason to measure salivary levels would be when the “provider” (frequently a pharmacist or chiropractic) does not have the capability for venipuncture. There is NO proven advantage to testing salivary levels for these hormones. In fact such levels are notoriously unreliable. Don’t waste your time and money!

Women whose estrogen levels have dropped significantly MAY have symptoms related to the decline and to the low levels. Such symptoms may include vaginal dryness or soreness with intercourse and vasomotor symptoms (hot flushes.) The FDA has approved many estrogen formulations (pills, patches, vaginal preparations, gels and creams) to treat these symptoms. But what about all the other unpleasant feelings that may accompany menopause? What about not sleeping, feeling irritable, loss of energy, depression, loss of sex drive? GOOD QUESTION !! Unfortunately, not only do I not know the answer, but I will go so far as to say that NOBODY knows the answer! There are plenty of “providers”- doctors, nurse practitioners, chiropractics, pharmacists, and “hormone replacement centers” who might CLAIM to have the answers, but I would caution you to beware of anybody making such claims. YES it is possible that you might get the perfect cocktail of hormones implanted under your skin or rubbed on your body to make you feel fine, but I think the process to finding a solution needs to be individualized, careful, and gradual.

So, the first thing to realize is that when the ovaries stop working, many women have little if any related symptoms. In fact many women feel better than they have for years. Breast tenderness resolves, swings in mood stabilize, headaches decline, and pain related to endometriosis or menstrual cramps finally melts away! Some find it easier to lose weight when there is no estrogen and less testosterone around.

But for many (if not most) women, the time around the PERImenopause is fraught with a sense of not feeling well. As mentioned above, there can be insomnia, irritability, fatigue, sexual dysfunction, and symptoms of depression. So where do you begin? Well I do believe hormone levels (estrogen, testosterone, and FSH) are a good place to start, but more as a baseline than to guide therapy. Since there is a very wide range for what is considered “normal,” I am likely to start estrogen therapy on a perimenopausal patient who has symptoms, regardless of levels. I think estrogen therapy is the key – the place to start the quest toward feeling better, once the patient understands the indications, risks, and benefits. It is preferable to start a patient on a single agent and tweak it to its most appropriate dose and route, then consider adding other therapies. It is highly likely that many of the complaints that plague the perimenopausal patient will improve or resolve with estrogen alone.

What about progesterone? Well first off, there is no usual reason to be checking progesterone levels in the nonpregnant woman unless it is to ascertain whether the patient is ovulating. It is expected that progesterone levels will be nil if estrogen levels are low. In general, despite what you might read or hear to the contrary, progesterone does not usually make women feel better, unless that premenstrual bloating, swollen feeling is the goal. That is why there are SO many birth control pills – manufacturers are trying to minimize the side effects of the various forms of progestins (progesterone-like-hormones) which are necessary to make the pill effective. (The very popular pill Yaz is indicated for PMDD treatment because the progestin it contains has some diuretic effects that make women FEEL better than they usually do premenstrually.)

What about women who are having regular periods but are feeling “hormonal?” Do they need more hormones, and which hormones do they need? Well that is an interesting and very difficult question to answer. If we were to measure hormones in ovulating, normally menstruating women, we would almost certainly find normal levels. The menstrual cycle is proof that there is adequate cyclical estrogen and progesterone. Menstrual ABNORMALITIES, on the other hand, demand demonstration of normal ovarian function. So what is the point of measuring hormone levels if periods are normal? It gives the doctor something to do, and leads either to confusion or reassurance, and is a waste of money. But what about my irritability, anger, lack of energy and sex drive, weight gain and acne? Those are some big questions with big answers, but not simple ones. Mood dysfunction might be a good topic for another blog; but I should clarify my opinion that anxiety, depression, PMDD (premenstrual dysphoric disorder,) chronic fatigue, and rage reaction are not synonyms for “hormonal.”

So who should get hormones, and why, and how? That is the guts of this essay topic. Let’s remember that normal women have their own hormones from puberty to menopause. We have to have a pretty good reason to mess with the system that is in place for normal reproductive function. One of the main reasons is birth control. Birth control pills, patches, vaginal rings, injections and implants are essentially synthetic “hormone-like” (not naturally occurring) molecules given to override the normal ovarian hormone function. Some of these methods are a combination of estrogen-like and progesterone-like “hormones;” some are progesterone-like only. (To be effective, these molecules are necessarily more potent than native estrogen and progesterone.) While the primary purpose of these “hormone” medications is to prevent pregnancy (through several pathways), there are effects related to these medications which have caused them to be used for non-contraceptive reasons. One such reason is to decrease the amount of menstrual flow and menstrual pain. Other indications are to decrease acne and improve PMDD. Some of these methods can actually safely lead temporarily to complete absence of menstrual cycles, a source of great relief to many women, but not desirable for all. The way that “the pill” helps with acne actually has to do with decreasing free testosterone blood levels. The pill causes an increase in a protein which binds this testosterone and therefore makes for lower levels seen by the oil-producing glands of the skin.

“BUT I THOUGHT TESTOSTERONE WAS GOOD !?” Well, testosterone IS good if you are male. A little testosterone might be good if you are a female, but a little bit goes a long way. Unless very closely monitored, testosterone therapy in women can lead to overdosing. This brings up the whole “HRC” question. Here in Nashville, a doctor (whom you can investigate to learn more about) and his businessman brother started and heavily marketed a business of implanting women (and men) with various hormone pellets, but especially testosterone. This practice was outside the scope of FDA approved therapy, but that doesn’t mean it was illegal. This business was investigated by the office of the Tennessee Attorney General, and I was advised to refer my patients to this office for consideration of seeking restitution. When I saw my first HRC victim, I called the doctor at HRC about the complication the patient was experiencing. It was at this time that I learned that HRC actually stood for “Hair Replacement Center.” This doctor was in the hair transplant business! Well I don’t know how that line of business was flourishing, but I do know that giving women excessive doses of testosterone is an excellent way to induce irreversible male-pattern baldness. I have seen thinning of scalp hair, deepening of the voice, increase in chest and facial hair, weight gain, pathologic enlargement of the clitoris, and breast cancer in various patients who were implanted with hormones at HRC. While I make no claims of causation, I can tell you that the patients I have seen with complications were not educated as to the potential to experience such bad outcomes.

But what about my sex drive?! I’ve heard that testosterone implants lead to great sex! Yes, that might be the case. But you can’t have your cake and eat it, too. Re-examine the list of side effects listed in the paragraph above. If you (and your doctor) decide on some sort of testosterone therapy, you are probably going to use a medication “off label,” meaning not approved by the FDA for that use. The FDA has examined and denied application for testosterone patches for improved female sexual function. That means that the experts at the FDA did not believe that the potential benefits outweighed the potential risks of therapy. That does not mean that testosterone therapy won’t help an individual patient, but it does mean that such therapy will require individualization and very close monitoring of side effects and efficacy. This therapy will not be standardized by a well studied protocol, but would be more like trial and error based on patient’s response to therapy.

What are the risks of hormones? Do hormones cause cancer? WOW big question. Yes and no. It is well known that estrogen alone might cause endometrial cancer in women with an intact uterus. That is why, with ongoing estrogen (E) therapy, the endometrium should be evaluated regularly or “protected” by administration of a progestogen (P) to stabilize or slough off the endometrial lining. There is a lot of controversy surrounding the results and interpretation of the WHI (Women’s Health Initiative.) The WHI was a large study of postmenopausal women seeking to prove whether estrogen +/- progestogen therapy might be good for prevention of heart disease. Several other disease processes were evaluated in this study, including colon and breast cancer and hip fracture. If I could summarize and simplify and extrapolate this study into a very few lines, I would say that estrogen appears to be safe and BENEFICIAL for women if started soon after menopause and if they do not require daily progestogen therapy for endometrial protection. If a daily combination E/P therapy is necessary, there MIGHT be as much as a 10% increased risk of breast cancer. There are strategies to avoid progestogen therapy, or to limit its use, thereby possibly negating this increased breast cancer risk. Women remote from menopause, having not seen estrogen for several years, might be at increased risk for a blood clot, stroke, or heart attack. This is not surprising. We have long known that increased estrogen levels of pregnancy and birth control pills increases risk of blood clot. Women in their sixties have had time to develop cholesterol plaques in their arteries, and making the blood more coagulable would naturally seem to increase that risk. What we do not know is whether there might be a protective effect on the vessels of those women who begin and continue estrogen therapy soon after menopause. That suggestion is a reason to consider estrogen early, when symptoms are present, and move toward lowering doses and discontinuation in subsequent years. The KNOWN benefits of estrogen therapy are decreased risk of hip fracture (osteoporosis) and colon cancer, as well as relief of hot flashes and vaginal dryness / atrophy.

In terms of testosterone therapy, the risks of many side effects are listed above, but it is important to remember that lipid profiles (cholesterol patterns) are likely to be detrimentally affected in women with hyperandrogenism (too much testosterone or similar male type hormones.)

So which estrogen should I take? What about bioidentical hormones?
Bioidentical is simply a nifty marketing term. It implies a hormone formulation that is biochemically indistinguishable from the hormone made in a woman’s body. There are actually a multitude of available “bioidentical” estrogen and progesterone formulations available by prescription and approved by the FDA. These come as pills, injections, patches, creams, gels and vaginal rings. The fact that a therapy is identical to a naturally occurring hormone does not mean that the medication was naturally formulated. Most hormone therapies are derived from plants, but are synthesized in a lab. The closest thing to “natural” hormones would be Premarin, derived from “PREgnant MAre urINe,” horse pee. It is frequently my first choice, and millions of women have been well served by that medication. It is the most studied form of hormone replacement, and the primary subject of the Womens’ Health Initiative.
What I do not, in general, recommend is for a woman to go and have her medications compounded by a pharmacist when there is available a similar, affordable, FDA approved medication manufactured in an FDA monitored facility. If you have ever seen “It’s a Wonderful Life,” you have seen what could happen when a compounding pharmacist is having a bad day. Why would you want to rely on the uncertain supplies and potentially inconsistent techniques of formulation of an individual when you can have very consistently precise, safe, and dependable formulations made in a modern manufacturing facility? Medications are not like food, where the closest thing to homemade is better. Medications are more like ammunition, where precision and consistency are essential to safe use.

It is important to understand that the topics covered in this essay are very complex, and you should talk to your doctor (not your hairdresser or your grandmother) to get your questions answered to your satisfaction.