Everything You Ever Wanted To Know About Hormones But Didn’t Know How To Ask

In women, testosterone is made in the ovaries (90%) and adrenal glands (10%). Testosterone is similar to estrogen in structure, however, it does very different, but complementary things for the body. Testosterone is actually quite nimble. Like estrogen, it can convert to other molecules. It can convert to estrogen as well as another hormone called 5-DHT. This is a more potent version of testosterone, which primarily shows its effects in the skin — for instance, it can cause acne and male pattern baldness. But 5-DHT cannot be converted into estrogen; it is too “manly.”

So, what happens when  testosterone levels starts to decline? (This usually happens in woman’s thirties). First, woman start to notice less tolerance for stupid people and the stupid things people do. People  lose your coping mechanism for life and sometimes, their filters. They start to become irritable and more moody. Some women become overtly depressed or anxious. I have seen patients develop severe anxiety, panic attacks and even the feeling of wanting to commit suicide. Mostly, though, women just don’t feel anything anymore — they’re apathetic. They wonder, “Is this is all life has to offer?” They say, “I have a wonderful life, I love my kids, I love my husband, I love my job, so why am I so unhappy?” Often, if they say this to doctors, they get prescribed antidepressants or, if they don’t seek help, they may end up in divorce court.

I honestly believe that many couples break up when women start going through perimenopause and it’s largely due to testosterone deficiency. These women feel different, and in turn their husbands may start to feel neglected. It’s not the women’s fault — it’s simply the testosterone deficiency wreaking havoc on their moods and brain. Testosterone is Mother Nature’s serotonin and affects how our brain processes information and how we feel. Most antidepressants increase serotonin levels so we can feel better. However, testosterone does this same thing and most women don’t need antidepressants if they get testosterone replacement.

We almost certainly think of testosterone’s role in the libido. Testosterone fires in the sexual centers in brain’s limbic system (the innate, primal part of the brain) and promotes the desire for sex. Think Austin Powers: “Do I make you feel horny? Yeah, baby!” Without testosterone, we do not have or feel this “horniness,” and this often leads to no desire at all. We love our partners, but just don’t have it in us anymore to want sex.

That’s why it’s common for women to question, “I love my husband, but am I ‘in love’ with him?” and it can have devastating consequences. Women start to think it’s a relationship problem, when it’s really a hormone deficiency issue. However, over time, deficiencies and self- doubt can lead to relationship issues, because sex is the driver for emotional intimacy and physical connection between partners. It is what separates us from being “just friends.”

Testosterone also makes our genitals (particularly the clitoris) spark with sensitivity and pleasure upon touch, hopefully leading to that almighty “O.” It helps with intensity and longevity, and boosts our ability to climax more quickly. It provides the vestibule (the area surrounding the opening of the vagina) with lubrication, and enhances pleasure. It helps the uterus contract during orgasm, increasing intensity of the sensation. Without testosterone, everything takes longer and may be lackluster. Pair these physical responses with lack of desire, and it’s really going to mess with woman’s heads. Our poor partners can’t compete with a brain that feels nothing, and then when you finally do give in to sex, it simply doesn’t feel as good as it once did. This opens the door for potential marital problems and affairs.

Testosterone is also essential for normal brain function, and in particular, executive function thinking. What’s that? It helps us retain information, drives our short-term memory and recall, and the ability to process new abstract ideas. It gives us that “killer instinct” and the motivation essential to survival in a rapidly progressing work environment. Estrogen may help all the brain centers communicate with one another, but testosterone is specific to executive function. In other words, testosterone is the hunter and estrogen is the gatherer. When levels drop, it’s no wonder our brains get foggy. Women think they are losing their minds and often become concerned that they’re developing early Alzheimer’s disease or dementia. Replacing testosterone helps maintain the brain’s top performance.

For all the good, important tasks testosterone accomplishes, its most important role is to help us burn sugar. It helps prevent weight gain, as well as insulin resistance (a/k/a pre-diabetes). When we eat a meal, the food is digested, and converted into glucose to fuel our body. The speed of glucose conversion depends on the type of food we eat. For instance, if we eat a candy bar, our glucose levels spike very high immediately. This is challenging for the pancreas, as we end up using more insulin more rapidly, which in turn, causes very high and then very low blood sugar levels. These effects of these massive swings cause more harm to the body. As blood sugar drops, we start craving sugar, and the body begins to store more glucose as fat. Eventually, the ups and downs lead to pancreatic burnout. Now, we’re entering weight gain territory, then it’s on to pre-diabetes, and if left unchecked, we’ll eventually arrive at diabetes.

So, how does testosterone affect sugar and pancreatic function? First, testosterone helps us move any immediate sugar in the bloodstream into the muscle, so the muscle can burn it cleanly. Second, testosterone helps us make more muscle cells so we can burn more sugar. This is why men lose weight faster than women. They have more muscle and more testosterone. Men are biologically set up to burn sugar easier than women.
Many of my patients come in with pre-diabetic blood sugar levels, and within one month of treating them with testosterone, their sugar levels are normal. They were never truly pre-diabetic; it was simply a sign of testosterone deficiency. However, many providers don’t realize this, and they start getting on our case to eat better and exercise (yeah, right — as if we weren’t tired and busy enough). After we fail, they suggest you start medications like Metformin, which helps regulate blood sugars in prediabetics and diabetics.
If you’re keeping track, the doctor now has us on antidepressants, anti-anxiety medications, diabetes medications and any number of supplements to help our memory and sex life. Better living through pharmaceuticals? It is depressing to know that so many of my colleagues are using medications as Band-Aids for symptoms of testosterone deficiency. These symptoms could be eliminated and good health restored if we simply gave women proper testosterone treatment for deficiencies.

Estrogen’s prime role in the body is for reproduction. We are born with eggs in our ovaries to propagate the gene pool. After puberty, every month the brain stimulates the ovaries to start maturing an egg for release and potential fertilization. It does this by increasing the level of estrogen in the bloodstream. Levels of estrogen must get high enough each month to allow for ovulation. If your ovaries don’t make enough estrogen, you won’t ovulate. This is why women’s periods are very erratic when we’re entering puberty and ovaries are new to the job, and again as we go through the phases of menopause. Initially, the ovaries are learning how to work, and at the end they just get tired, and our periods once again become erratic. When our period finally stops and the ovaries retire, we’re in menopause. But estrogen doesn’t just stimulate egg formation: It also helps the uterus prepare for the egg to implant by thickening the lining, and also improves genital health, allowing for comfortable and pleasurable intercourse.

However, when estrogen isn’t helping the ovaries prepare for reproduction, it helps the body in many different ways:

• It helps prevent our bones from breaking down, keeping them strong, and works with testosterone to promote new bone growth.
• It stimulates collagen growth and helps keep cells hydrated, resulting in soft, supple, healthy skin.
• It facilitates proper communication between brain cells, keeping our mental function sharp.
• It protects us from heart disease by improving electrical conductivity, strengthening muscle cells, and increasing the heart wall function. It also keeps our blood vessels flexible by promoting endothelial wall dilation within the blood vessels.

These processes, along with hundreds of other day-to-day body functions all rely on proper estrogen levels. Without it, our bodies start to age rapidly and outwardly, we begin to show visible signs of aging. Our bodies begin to break down internally as well, putting us at higher risk for chronic illness.

Estrogen evokes fear in many, including too many medical professionals who should understand how it works in the body, but really don’t. The key to understanding why bio-identical estrogens are safe is that not all estrogens are created equal. Cells in our bodies respond differently depending on the type of estrogen present and which cell receptors are on that cell taking in the estrogen. Think of a lock and a key. The estrogen is the key and the receptor is the lock. Some estrogens fit nicely into some locks, but not others. You need the right combination to open the lock in order to create the right positive effect for the body. Each woman has a different balance of keys and locks — none of us is exactly alike. That’s why we shouldn’t (and don’t) prescribe the same doses of bio-identical hormones to every woman.

There are many different estrogens, but for simplicity’s sake, we will talk about the big three: Estrone, estradiol, estriol.

Estrone (E1) – This is a moderate strength estrogen made in our fat cells. If we’re overweight, an enzyme called aromatase converts estradiol to estrone in the fat cells. Estrone is weaker but more toxic, which is why more overweight women will have more breast cancer. If you’re overweight, you shouldn’t take too much estradiol because it will convert to estrone.

Estradiol (E2) — This is the good, strong estrogen. It keeps us feeling great and keeps our body healthy. This is the one we want to replace. This is the estrogen contained in the Climara and Vivelle-Dot patches, troches and pellets commonly use in hormonal specialty practices.

Estriol (E3) – When pregnant, women make large amounts of estriol, and also in minute amounts when we’re not pregnant. It’s very weak and helps balance overall estrogen by blocking estrone’s effects on estrogen- responsive cells, which is why some doctors and researchers think it protects the breasts. However, when this estrogen breaks down it makes a metabolite called 16-alpha hydroxyesterone that’s toxic to breasts. Some providers don’t prescribe it because of this conversion. Based on common sense biology, I believe that it is more likely to be protective because it’s the hormone that protects both mother and baby during pregnancy. How it does this is not well understood.

In addition to having three different estrogens, women have different estrogen receptors that accept these estrogens differently. These are called ER alpha receptors and ER beta receptors. They’re largely found in the breasts (Mother Nature’s breast augmentation), heart, blood vessels, the uterine lining, brain cells, and bones. In fact, these receptors are found in almost every cell in the body.

ER alpha receptors are the “stimulator” receptors which cause growth in various systems in the body. ER beta receptors are the “dampening” receptors which are responsible for keeping ER alpha in check, by prompting cells to relax so they don’t grow unregulated. When cells become unregulated, they can begin to rapidly multiply, resulting in uncontrolled rates of growth. Ultimately, these cells have the potential to mutate and become cancerous.

For example, the breasts and uterus contain both receptors, but ER beta receptors are most predominant. ER alpha receptors take in estrogen, causing the breast tissue and uterine lining to grow during certain times in our cycle, as well as reproductive lives. As we learned earlier, the ER beta receptors fend off the ER alpha so that the cells don’t grow out of control. The more ER beta signaling there is in the breast and uterine lining, the fewer incidences of breast and uterine cancer.

So the ER beta protects lung tissue, the ovaries, the colon, the immune system, the bladder, the brain and serotonin neurotransmission, and every other cell in the body, just like ER alpha receptors. We need both receptors to live happy and healthy lives. However, the ER beta receptors are the ones specifically responsible for helping to prevent cancers in women.

ER alpha signaling is increased by: being overweight, eating a diet that’s high in junk foods, increased levels of stress, exposure to synthetic estrogens, excessive alcohol consumption, low functioning thyroid (another reason to replace thyroid), vitamin D deficiency and bad genetics.

If you consider the three estrogens previously mentioned: Estrone binds more strongly to the ER alpha receptors, causing more cell growth and increasing the risk of cancer. Estriol binds more predominantly to ER beta receptors, decreasing cell growth and the risk of cancer. Estradiol is well balanced between ER alpha and ER beta. This balance makes it the ideal estrogen for promoting good cell growth in tissues, but it knows when it needs to take a breather.

Given this information, it makes sense that women with estrogen deficiencies need the good, well-balanced estrogen that helps promote healthy, stable growth in tissue, while simultaneously keeping cell growth in check. This is why I prescribe estradiol for women — the bio- identical “good,” strong estrogen.

Many pharmaceutical companies are trying to make “designer” estrogens that positively affect the ER alpha receptors, while using ER beta control on the bad effects of overstimulation. Medications such as Tamoxifen help protect the breast, but still have the negative alpha effect on the uterus, increasing the risk for developing uterine cancer. Raloxifene provides the positive stimulatory effect on ER alpha on the bone, and a positive ER beta effect on the breast and uterus. Like Tamoxifen, Raloxifene provides breast protection, but unlike Tamoxifen, it does not increase the risk for uterine cancer.

Once you understand the types of estrogens and estrogen receptors, you better understand the benefits of these drugs, as well as their potential side effects.

Progesterone can be annoying, but like the nagging sibling, you really need her in your life, you just have to find the balance. When she’s not around, you start to notice. Your periods stop coming regularly, and you’ll be left wondering what’s happening to your body. Without progesterone, all of your hormones will be out of balance, and you won’t feel well.

Let’s go over the details of what progesterone does and how it acts in the body. It has many functions, but its biggest and most important job is to prepare the body for pregnancy. During our reproductive years, the pituitary gland in the brain generates hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). These cause a new egg to mature and be released from its ovarian follicle each month. As the follicle develops, it produces estrogen, which thickens the lining of the uterus. Progesterone levels rise in the second half of the menstrual cycle, and following the release of the egg (ovulation), the ovarian tissue that replaces the follicle continues to produce progesterone.

So to review, estrogen stimulates growth of the uterine lining, causing it to thicken before you ovulate each month. Progesterone gears up in the second half of the menstrual cycle, getting everything prepared for pregnancy; causing the endometrium to secrete special proteins, preparing it to receive and nourish an implanted fertilized egg. If the egg doesn’t implant, estrogen and progesterone levels drop, the endometrium breaks down, and we have our period.

If a pregnancy occurs, progesterone is produced in the placenta, and levels remain elevated throughout the pregnancy. The combination of high estrogen and progesterone levels suppress further ovulation during pregnancy. Progesterone also primes the breast to be able to deliver milk for breastfeeding.

In order to ovulate, you need adequately high estrogen levels during mid-cycle. If you don’t ovulate, you won’t produce progesterone. You might say, “Hey, that doesn’t sound so bad. If I don’t get enough progesterone, I won’t have PMS, right?” Wrong. Everything has to work in concert. If your estrogen is chronically low, especially to the point where you’re not having periods, it also can make you weepy, bloated and cause breast tenderness – similar to PMS.

The idea is to keep everything in balance. Think of the three hormones as siblings. Testosterone is the happy-go-lucky brother who keeps the peace between estrogen (the beautiful, popular sister everyone loves) and progesterone (the ugly stepsister). When they’re all together and doing their chores like they’re supposed to, the body is happy. Unfortunately, during perimenopause, testosterone is always the first to move out of the house, so the brother who would normally keep the sisters in line is nowhere to be found. That makes the symptoms from the fluctuating estrogen and progesterone levels even worse. And that, my friends, is why perimenopause sucks.

High thyroid (a fast engine), often called overactive thyroid (hyperthyroid), can also cause fatigue, along with diarrhea, intolerance to heat, sweatiness, nervousness, anxiety, high blood pressure, itching, rapid or irregular pulse, difficulty sleeping and weight loss. Although I know many women who would love to have a race car engine because it speeds up metabolism, it’s just as damaging to the body as low thyroid.

Low functioning thyroid, or hypothyroidism, is much more common than hyperthyroid. Estimates range, but approximately 1 in 3 women and 1 in 5 men will have a low functioning thyroid (hypothyroidism) by the time they hit 50. Many women I meet are hypothyroid and have no idea, because they’ve been tested and told their thyroid is functioning fine.

So what makes these hormones that control so much of how we feel? It’s the thyroid gland, a bow tie-shaped gland in the front of our neck. If it gets swollen, we call it a goiter. This can happen with both low and high thyroid, but it’s most commonly found with low thyroid. It’s easily treatable and not serious in most cases. Once you get the proper thyroid medication, it’s resolved.

The brain is the thyroid’s boss. The thyroid’s job is to secrete a molecule (or pro-hormone) called T4. When it’s making enough T4, the brain sends the thyroid a signal that says “Yep, everything is A-OK up here,” so it keeps producing the same level of T4. If it’s not making enough, the brain sends out TSH, or thyroid stimulating hormone that says “Hey, lazy! Ramp up the production!” and in response, the thyroid begins pumping out more T4.

Unfortunately, this is only half the story, but it’s usually the only half doctors check, which is why the hypothyroid diagnosis is so often missed.

Many women make enough T4, but the problem is that T4 is an inactive molecule that needs to convert to its active T3 form. T3 is the molecule that triggers a response in the body’s cells. Every cell in the human body has receptors that accept the T3 molecule. If the T4 does not properly convert to T3, the thyroid can make all the T4 it wants, but it will never trigger the appropriate cellular responses. They simply won’t fire properly.

To make matters worse, there’s a little decoy molecule called reverse T3, which can sit in the thyroid receptors on the cells, blocking the active T3 molecule from docking and talking to the cell. If you block T3 from getting into the cell’s receptors, the cells never activate. This means you can have normal thyroid function, but since the T3 cannot enter the cells, you are ‘functionally hypothyroid’ on a cellular level.

To recap, there are three ways the system can go awry:

1. You don’t make enough T4. This is easy to spot, because doctors commonly test for T4 levels, and the brain hormone TSH (thyroid stimulating hormone) will show up as high. If the thyroid is not doing its job, the brain uses TSH to whip the thyroid into manufacturing more T4. The lazier the thyroid is, the more it gets beaten into producing more. (Picture the TSH as a mean boss with a whip, and the slower the worker, the more he gets whipped.) Since most doctors only check for TSH and T4 levels, if they don’t see anything wrong, they say the thyroid is fine. But they’re missing the most essential parts of the picture.
2. The inactive T4 does not convert well to the active T3. The enzyme 5-deiodinase is necessary to convert T4 into active T3. Without enough of this enzyme, your body won’t be able to “kick” the extra iodine molecule off the T4 to convert into the active T3. Too much iodine in the diet or in supplements can inhibit this process.
3. The active T3 can’t get into the receptors. If a doctor doesn’t check T3 and reverse T3 levels, they cannot get the true picture of a patient’s thyroid health. Many of my new patients present with a full set of symptoms consistent with low thyroid, and the clinical exam that supports this, but their T4 and TSH levels are normal. However, if I look at T3 and reverse T3 levels, I can easily see the problem. Most often, the body isn’t converting T4 to active T3. But some women have too much reverse T3 blocking the receptors. This can be caused by medications, adrenal dysfunction, stress and other factors.

Some women have just one of these thyroid problems, but many have all three issues.

A less common disorder is too much thyroid, or hyperthyroidism. This is the exact opposite of hypothyroidism. The thyroid makes too much T4, and the whole body is hyper-activated. Lab tests will show too much T4, too much T3 and a very low TSH. (The TSH doesn’t need to whip the worker, because he’s already working fast and hard, so labs will show decreased levels.)

As you can see, unless all of the levels are tested, you can’t properly diagnose thyroid disorders, and hypothyroidism is the one most often missed. Luckily, hypothyroidism is usually not difficult to treat. It requires taking a pill each day. However, an incomplete diagnosis will affect proper treatment of the disorder. For instance, a doctor might give a patient medication solely to increase T4. But it won’t matter if you’re not successfully converting T4 to T3, or if you have a lot of reverse T3 blocking the effects of T3. You can give someone all of the T4 in the world, but the patient will never improve. You need to administer T3.

From the early 1900s, a common thyroid pill made by Armour (from crushed-up pig thyroid) containing T4 and T3 was used to treat hypothyroid. The first ever thyroid medication, it was effective and widely prescribed. Today, the most popular medication used to treat thyroid in conventional practices, including endocrinologists, is a synthetic hormone called Synthroid. Made by a large pharmaceutical company, it’s the top-selling thyroid medication in the U.S., and one of the top-selling drugs in America. The problem is that Synthroid only contains T4. So if you’re hypothyroid and on Synthroid and you still feel terrible, it’s not your imagination, it’s a matter of simple chemistry.

If you have a T4 disorder, Synthroid is fine, but if you don’t covert T4 well to T3 or you have a lot of reverse T3, you need to take an additional medication called Cytomel (which is pure T3) or better yet, use a drug like Armour, which contains both T3 and T4.

So why is this less-effective medication so popular now? After Synthroid was launched, the company began an extensive marketing and rewards campaign inside the medical community, using authoritative figures to create brand loyalty. Gradually, many endocrine societies and even endocrinologist experts began stating that Armour should not be used.

Today, medical students are taught in schools not to prescribe it. But it’s all hogwash, pardon the pun, because Armour is safe, effective and cheap; and most of my patients don’t mind that it’s made from pigs. I do have some patients who are highly allergic to certain substances and can’t take pig thyroid, and some Jewish patients who don’t wish to take it because of religious observance. But roughly 90 percent of my patients are on Armour and they do very well.

Big Pharma has a vested interest in making Synthroid the go-to drug for low thyroid, even when it doesn’t effectively address the patients’ problem. If you take Synthroid and don’t feel better and your doctor refuses to prescribe anything else, see another doctor.

One size does not fit all in medicine, and when it comes to hormones — including thyroid — this definitely holds true.