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What You Need to Know about Hormone Replacement Therapy


Puberty occurs with a rise in sex steroid hormone production in men and women. Puberty lasts for several years and then adult stature and physiology occur. Women receive hormonal support primarily from the ovaries and some from adrenal gland activity to make estrogen, progesterone, and a small amount of testosterone. Men rely primarily on the testicles to produce the male hormone testosterone with small amounts of estrogen produced in the adrenal glands, and some produced by an enzyme (found primarily in abdominal fat) that converts testosterone into estrogen.

The onset of menopause

During peak reproductive years, women produce enough hormones to regulate menstrual cycles, support pregnancy, maintain organ-system health, and sustain optimal brain health. Men produce enough testosterone during this time to produce sperm and maintain strength endurance, muscle mass, mental clarity, and healthy organs.

Hormone production and supported functions work well until perimenopause (the transition to menopause) occurs. When this happens, women begin to experience symptoms of hormonal deficiency as the production of estrogen, testosterone, and progesterone declines. Eventually menstrual cycles cease, and menopause has officially arrived.

During menopause, most women only produce very small amounts of essential hormones. Perimenopause can last for several years with dwindling periods, hot flashes, night sweats, and other symptoms. When menopause occurs (no more periods), many women quit having hot flashes and think they are through menopause. Actually the lack of periods is only the beginning of menopause.

The “change” that is often discussed for aging women is really perimenopause when hormone production declines and symptoms begin to appear. These changes mark an irreversible process leading to menopause that is forever accompanied with diminished hormone production.

The onset of andropause

Men tend to have a less dramatic change we refer to as andropause. Male hormone production (mostly testosterone) begins to decline beginning in the mid to late 30’s and typically drops at a rate of 1-3% per year. For most men, there are few symptoms to indicate this decline until a tipping point occurs that causes the demands of life to exceed the body’s ability to respond hormonally. It does not happen to all men, but does occur in about 50% at age 50, 60% at age 60, 70% at age 70, and so on.

We know that there are ranges of normal concentrations of hormones in our bodies during our peak reproductive years, in a range of approximately15-50.  We also know that during this time the hormones are doing remarkable and healthy things for our bodies to function properly. So…. when menopause or andropause occurs, we look at it as an opportunity to re-introduce appropriate hormone therapy to obtain and maintain hormone levels appropriate to the health reproductive state.

Healthy hormone levels

For instance, if a man has a testosterone level of 800 or 900 ng/dl at 40 and it is healthy for him, then a similar level is healthy for him at 60 years of age.  However, his natural production may only produce to a level of approximately 300 ng/dl. This is considered in a normal range for a 60 year old by many labs, but it is not a functionally healthy level for a 40 year-old male generally. Similarly for women, if a healthy estradiol level is 150-450 at age 30, it is also healthy for a 60 year old, if it is introduced into the body appropriately.

One of the hormone levels we follow is the FSH or follicle-stimulating hormone produced in the pituitary gland in the brain, for action in the ovary. We know that there is a fairly narrow range of normal FSH in the reproductive age group of women prior to menopause. The pituitary gland recognizes that the estrogen levels are declining and makes the FSH to stimulate the ovary to make more estrogen. If the ovary responds, the FSH level then declines and waits for more signaling to stimulate the ovary again.

If a 40 year-old woman were to inquire about her pregnancy capabilities with a reproductive endocrinologist, a test would be performed to assess her FSH levels. If the FSH level exceeds 10 or 12 ng/dl, the fertility doctor might tell the patient that her ovaries are beginning to fail. It would either take significant stimulation to cause ovulation and pregnancy. At this point, medical professionals often suggest surrogacy or adoption.

If a an FSH level of 10-12 or greater is associated with declining ovarian follicle production (and thereby low estrogen levels because that is where most estrogen is produced), it can be surmised that healthy FSH levels should be under 20 or so. Yet labs list normal FSH levels in menopause of up to 100 or greater! Several important medical studies have shown that women with such high FSH levels are at a much higher risk of dyslipidemia (abnormal concentrations of cholesterol and byproducts in the blood), heart attack, and stroke.

In fact, an important observation in Denmark by Dr E. Lookegarrd was published in the European Heart Journal in 2008.  She studied the medical records of 698,000 women who were followed for ten years beginning at the time of menopause. She determined that women who used bioidentical estradiol reduced their incidence of heart attack by 50 percent compared to women who took nothing. (Bioidentical simply means that the medication looks and behaves in the body the same as what the body would normally manufacture and use when healthy.) Additionally, women who took artificial estrogen products especially with synthetic progestin compounds, had a much greater risk of heart attack than women who took nothing for hormone replacement during the same time frame.

Determining optimal hormone levels

So, that brings us to the question of what IS appropriate. The best approach is to have the introduced replacement hormones look like those naturally produced, and arrive at target tissues looking as if they were produced inside the patient’s body. When this is done, it is healthy and can be done forever. This is the opinion of the most highly regarded physicians around the world who treat menopausal women and andropausal men. The International Menopause Society, the European Menopause and Andropause Society, the North American Menopause Society, and the American College of Obstetricians and Gynecologists, among others adhere to this recommendation.

Unfortunately, some of the more popular therapies are not ideal. One of the more popular estrogen therapies for women in the last 50 years has been conjugated equine estrogen (CEE)- an extract of pregnant mare urine! Female humans have been taking estrogen produced by horses. Women with an intact uterus are normally given progesterone to prevent unwanted stimulation of the lining of the uterus so menstrual cycles do not return.

In addition, one of the more popular progesterone-like compounds used in the past 50 years is medroxyprogesterone (MP), a synthetic compound with progesterone-like qualities. Yet, this compound was the culprit in the Women’s Health Initiative (WHI) that was the primary cause an increased risk of breast cancer in the women receiving CEE/MP arm of that study. We now know, after many years of further study, that the estrogen-only portion of the WHI study actually experienced a 20-percent decreased incidence of breast cancer compared to women who took only a placebo.

Choosing the best hormone replacement

It can be difficult to determine the best approach when there is so much misinformation, but here is a key takeaway: World-leading physicians who care for menopausal women and andropausal men advise it matters what you take and how it’s administered.

For example, when a woman swallows a natural estrogen or bioidentical estrogen product like estradiol (the most prescribed form of estrogen), the gastrointestinal tract modifies it by a process called conjugation. The conjugated estrogen travels to the target tissues for utilization. The problem is that this conjugated estradiol stimulates what are called acute phase reactants in the blood stream and promote an inflammatory-like response that increases risks for the blood to clot inappropriately, causing strokes and heart attacks.

By simply applying the same estradiol product to the skin, using an injection, vaginal application or subdermal estradiol pellet therapy, this first pass metabolic risk is eliminated. Important medical studies have confirmed that when this first pass metabolic process is bypassed, there is no additional blood clot risk with estradiol consumption.  The studies have not yet been performed for men using testosterone products, but similar conclusions can be drawn regarding how men use testosterone as well: topical, intramuscular, and subdermal pellet therapies are probably much safer than oral or non-bioidentical ones.

So, if and when it comes time for you to begin hormone replacement therapy, please ask your healthcare provider to consider the makeup of he product and how it will be delivered into  your body.

Other considerations before choosing hormone replacement therapy

Another aspect of menopausal hormone management is hormone blood level testing. It is important to differentiate between symptoms of hormone deficiency and hormone excess, as they can be similar. Only by quantifying the information with blood testing will your healthcare provider be able to accurately assess how best to manage your hormone replacement therapy.

I am often asked about saliva testing. Unfortunately, common saliva testing has not lived up to the promise of accurately providing information that is useful for medical management of menopause. There are only a few labs who devise very special evaluations of saliva, including one Dutch Lab.

Other questions I  get asked: how about black cohosh or aroma therapies? Or even tofu or other phytoestrogens (plant-based compounds that have an estrogen-like effect).  Or how about taking an antidepressant for symptom relief? All of these therapies have a place in managing menopause or andropause. The problem is they are only treating symptoms.  No one has a clinical deficiency in black cohosh, or Prozac, aromatic oils or tofu.  And our brains do not recognize the signaling needed to respond hormonally to these messages.


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