Guide to Hormone Replacement Therapy for Women
The dramatic decrease in estrogen that accompanies menopause in women has been well documented. Reduced estrogen can cause many negative effects for women’s health, including increased risk for heart disease, osteoporosis and other diseases. To address these symptoms, many women have opted for hormone replacement therapy (HRT) to compensate for low estrogen levels.
Over the years, some media articles highlighted and overstated the ramifications of taking HRT, causing alarm for many women. The results of the Women’s Health Initiative Trial (WHI), for example, generated a great deal of debate and controversy. As a result, many women avoided hormone therapies, choosing instead to endure the debilitating symptoms of menopause and accept the increased health risks after menopause.
To quell fears and establish the facts behind the study, a number of physicians thoroughly examined a large volume of research data to determine whether the reports were indeed founded or whether they were causing unnecessary alarm. Their investigation unearthed many facts suggesting the media overgeneralized many of the risks associated with HRT. The WHI studies, for example, only evaluated two drugs, provera and premarin, and only focused on a specific age group, including women who began their treatment during the later stages of menopause.
Since then, a growing body of research has emerged affirming the safety and efficacy of hormone replacement therapy that is individually tailored and closely monitored. Indeed, traditional methods of HRT tend to be less advanced than conventional medical treatments for conditions such as hypertension and diabetes. Traditional HRT is applied in a comparatively archaic fashion, without proper attention to individualizing therapy programs or monitoring the results of the therapy. Today, HRT treatments are increasingly refined, using bioidentical hormones that are safer and more effective than those used in older HRT treatments.
A number of factors contribute to successful hormone replacement therapy, including the means of administering the hormones, regular monitoring of hormone levels, continued adjustments over the course of treatment, and the balance of hormones with other hormones that also decline with age.
While WHI alarmed many people about the safety of HRT, it also helped to shine a spotlight on the therapy and generated important debate about the many issues that must be considered when deciding to start HRT. These issues are further discussed in the following sections:
Menopause is commonly understood to be the transition period when a woman stops having regular periods. The term can be somewhat misleading, however, because the process of menopause embodies a continuous spectrum of stages with variations in hormone levels throughout. Many terms exist to describe these various stages, including ‘perimenopausal’, ‘premenopausal,’ ‘menopausal,’ and ‘postmenopausal’.
Each woman’s experience can vary drastically based on the stages of menopause. One of the most common symptoms is the hot flash, which happens when estrogen levels have remained low for an extended period of time. Hot flashes are typically accompanied by difficulties with memory and concentration, along with vaginal dryness, dry skin, and dampened energy and libido. Bone density also begins to deteriorate. As menopause progresses and even after it is completed, the negative effects of reduced estrogen levels persist and may even worsen, increasing damage to organs. Other effects observed include increased risk for heart disease, diabetes, Alzheimers and osteoporosis.
Clearly, the risks associated with menopause are serious. Women are encouraged to learn about anti-aging treatments to begin treating symptoms before menopause begins, which can help mitigate the long-term consequences of reduced estrogen.
What is Estrogen?
Of the many estrogen molecules that exist in a woman’s body, the three main forms are estradiol, estrone and estriol. Estradiol is produced by the ovary and is the most powerful. Estrone is a metabolite of estradiol and is considerably less potent. Estriol is a further metabolite of estradiol and is the weakest of the three. Because every estrogen molecule produces its own effects on body tissues, understanding the distinctions is critical when it comes to choosing an estrogen replacement therapy.
What is 'natural' estrogen?
What does it mean to be a natural estrogen? This is a question commonly asked by women interested in natural HRT treatment programs. Answering this question requires understanding the distinction between estrogens that are naturally produced in the human body and “natural” substances that resemble estrogen. The former, known as bioidentical hormones, are the estrogens you want to include in your therapy. Bioidentical hormones are most commonly derived from diosgenin, a chemical that is found in yams and converted into human estrogens. Bioidentical hormones include estradiol, estrone, and estriol, and all of their metabolites.
Premarin, however, is an example of a substance that is natural (it is not chemically synthesized and is derived from the urine of pregnant mares) but is not naturally found in the body. Premarin is the most commonly prescribed estrogen composition in hormone replacement therapy and combines two estradiol and estrone with 10 or more horse estrogens. But because horse estrogens are “exogenous” to humans, their full effects on all tissues in the human body are not well understood and are also difficult to monitor. Monitoring the effects of estrogen therapy is critical, as hormone levels can change drastically as a result of treatment, creating unnecessary risks.
Below is a chart comparing bioidentical and non-bioidentical hormones.
The importance of transdermal route
Majority of women administer their hormone replacement therapy by mouth - a method that is convenient, but may actually be harmful. Taking an estrogen pill does not allow the hormone to be released gradually into the circulation, to mimic estrogen that is naturally released by the ovaries. When taken orally, a large amount of estrogens is introduced to the body at once, which can produce negative effects in the liver. The following risks are common among patients who take oral ERT as well as birth control pills:
1. Increased risks of blood clots. This led to label warnings that older women and women who smoke may have an increase in clotting.
2. Symptoms of low testosterone - decreased libido, vaginal dryness and thinner bones - due to a rise in the carrier molecule, 'sex hormone binding globulin.'
3. Muscle loss and fat increase resulting from a change in the metabolism of fats and protein.
4. Increased risk of breast cancer and other side effects when estrogen levels exceed that of normal menstrual cycles. Estrogen levels can spike three-fold if alcohol is consumed while taking oral estrogen. By contrast, alcohol consumption with transdermal estrogen results in only a 30% increase in estrogen level.
5. Increased risk of gall stones.
6. A rise in triglycerides and, subsequently, the risk of heart disease.
These side effects are not present when ERT is administered transdermally (through the skin), as the hormone dose is gradually released into the circulation. This more closely mimics the gradual release of estrogen when it is naturally produced in the ovaries.
So why aren't all women taking their ERT transdermally?
There a number of the reasons why many women continue to take HRT orally. Here are a few:
1. Inertia: Oral therapy seems easier and more familiar, while transdermal therapy is not as readily available. Transdermal therapies are not patentable, which reduces the incentives of pharmaceutical companies to develop and market them. Also, few physicians are trained to prescribe precision amounts of several hormones combined or to optimize them through analysis and dosage modification.
2. Convenience / Availability: Most women prefer not to wear a patch. But transdermal creams offer an effective alternative that provides steady estrogen levels through excellent absorption. It is worth repeating that pharmaceutical companies have no interest in marketing unpatentable products such as transdermal creams.3. Oral ERT raises HDL: It is true that oral estrogen therapy can generate a greater increase in HDL compared with other therapies. But even without estrogen replacement therapy, the majority of women already have a good level of HDL. Raising the level from 60 to 80 mg/dl does not outweigh the negatives.
Bioidentical Progesterone vs. ProveraThe majority of physicians who prescribe oral estrogen in standard ERT will combine it with Provera. While many physicians may tell you that Provera is progesterone, it is a misleading answer at best. To be accurate, Provera is medroxyprogesterone acetate, which is a natural progesterone that is modified with an extra molecule, making it patentable and also easier to absorb when taken orally. Still, the sudden release of hormones that is inevitable with oral ERT is one of the main reasons women decide to stop therapy, because it often causes mood swings and depression. By contrast, true progesterone improves one’s mood and has a calming effect, which is why many women switch to bioidentical micronized progesterone. Bioidentical progesterone also acts as a natural diuretic, whereas Provera users frequently complain about fluid retention and bloating.
Additionally, bioidentical progesterone is more effective against cholesterol and does not carry risks of reversing the artery-dilating effects of estrogen, as Provera has recently been shown to do. This finding may provide an explanation for recent “HERS” trials, in which HRT was found to offer less heart protection than initially believed. The progestin used in the HERS trials was Provera, not progesterone. The negative effects of Provera on the heart may explain slight rise in heart attacks among study subjects, though the cardiovascular issues may also have resulted from increased risk of clotting with oral estrogen.
Testosterone – Not just for men anymore!
Emerging scientific evidence affirms the extreme importance of testosterone for women, as well as men. But women need only one-tenth the amount of testosterone recommended for men. Women’s ovaries produce roughly 30 percent of the body’s testosterone, while the remaining 70 percent is produced from precursors such as DHEA and androstenedione. Both DHEA and androstenedione begin to decline as women age, bringing about a gradual reduction in testosterone. While a drop in estrogen has more severe health consequences for women, testosterone deficiencies can also lead to symptoms that closely resemble those of men: a drop in libido, dryness in skin and genital tissue, depression and reduced muscle.
At Youth Diagnostics™, we test the levels of testosterone in your body to determine whether you are testosterone-deficient. For women who have still have fully functioning ovaries, simply restoring DHEA levels often suffices in building up testosterone to youthful levels, as the ovaries still continue to produce testosterone, even after menopause. Our doctors may also add bioidentical testosterone to your ERT cream, to help restore testosterone levels to the appropriate range. For women who have had her ovaries removed, however, it is often necessary to use bioidentical testosterone replacement. The importance of testosterone in women is seen perhaps most powerfully in the effectiveness of treating bone density problems by adding testosterone, rather than estrogen - even in women who take oral HRT and have had their ovaries removed.
What about side effects and cancer risk?
Many reports of possible side effects and increased risks of breast cancer have scared many women away from hormone replacement therapy of any kind. But many of these fears are allayed when they learn about the facts surrounding these warnings.
The side effects widely associated with HRT are only present in traditional HRT therapies - they are virtually nonexistent in advanced therapy programs that are individualized, that prescribe only physiologic levels of bioidentical estradiol and progesterone, that administer hormones transdermally, and that closely monitor blood levels and responses to the treatments. Traditional ERT treatments that are taken orally and that use hormones derived from horse urine are difficult to monitor and prescribe precise dosages. They also carry greater risks of side effects and cancer than the transdermal bioidentical regimens we use at Youth Diagnostics™.
Among the most common side effects of ERT are breast tenderness and vaginal bleeding, which can often be reduced by simply adjusting the dosage of hormone. Testosterone replacement therapy can also lead to unwanted hair growth or acne, particularly among women who have had a history of either of these problems. Again, side effects become manageable when dosages are able to precisely achieve the proper youthful levels of hormones.
But perhaps the most serious concern about taking HRT over the long term is a fear of breast cancer. We cannot reiterate enough our belief that the media has grossly overstated the risk of breast cancer. Early studies concluded that a 65-year-old woman who has used ERT for a decade increases her risk of breast cancer from roughly 4.5 percent to 5.6 percent. This is a small risk increase when compared with the inordinate benefits of ERT in the woman’s health and overall quality of life. Moreover, even this small increase in risk can be significantly reduced by taking bioidentical ERT in the transdermal form discussed above.
The increase in cancer risk may also be explained by the studies that showed how alcohol can cause estradiol levels to triple for women who take oral estrogen replacement therapy. Data from the Iowa Women’s Health Initiative indicated a rise in breast cancer risk among women who take oral estrogen and drink at least a glass of wine each day. However, this does not suggest that women using estrogen replacement must abstain from alcohol. When bioidentical transdermal estradiol is used, alcohol consumption causes estradiol levels to rise by only 30 percent. This percentage can be further reduced and adjusted by customizing transdermal creams and monitoring blood levels appropriately.
DHEAS is an important hormone in the overall endrocrine system and is among the most critical hormones in any HRT program. DHEA is accessible over the counter, which has generated significant amounts of press coverage and has resulted in a glut of information that can be contradictory and confusing. Between adolescence and old age, the physiologic levels of DHEA in the human body gradually declines, a course that is correlated with numerous health hazards, including increased risk of heart disease among men, a hampered immune system for men and women, as well as reduced insulin sensitivity.
Scientific studies in which the level of DHEAS (the form found circulating in the blood) was restored to the levels of a 20-year-old have produced impressive results in older adults. It has also proven effective for people in various disease states where the DHEAS level is lower than expected for their age group. In a six-month study, Yen and Morales administered 50 mg of DHEA to a group of adults aged 40 to 70 years. The patients experienced a rise in lean muscle mass and a drop in fat mass, and had a notable increase in their perception of their psychological and physical well-being. Additional studies demonstrated positive changes in the body’s immune functions.
At Youth Diagnostics™, our physicians assess patients’ DHEA-S level and prescribe the necessary supplements to restore DHEA levels back to that of a 20-year-old individual. As with all treatments, we continuously monitor and evaluate DHEA levels once a patient is on therapy.
DHEAS is very safe and does not require a prescription. While no evidence suggests an increased risk of breast or prostate cancer, patients who have had either cancer should not take the hormone. Before starting DHEA therapy, our physicians screen patients for breast cancer. One side effect of DHEA includes increased hair growth and acne in patients who have had a tendency for acne as a teenager.
The thyroid gland produces thyroxine (T4) and triiodothyronine (T3) - hormones that help to regulate metabolism in the human body. The thyroid hormone that is most prominent in the blood is thyroxine (T4), which has a longer half-life than T3.
Thyroid hormones affect all cells in the body in a variety of important ways. These impacts include increasing the basal metabolic rate, affecting protein synthesis, regulating bone growth, improving neuronal maturation and affecting the body’s sensitivity to many other hormones. The body depends on thyroid hormones to ensure proper development and differentiation of all cells in the body. Many different physiological and pathological factors can influence the synthesis of thyroid hormones, which also regulate protein, fat, and carbohydrate metabolism, and stimulate vitamin metabolism.
Having too much or too little of thyroxine can result in hyperthyroidism or hypothyroidism. Hyperthyroidism occurs when too much free thyroxine and/or free triiodothyronine is circulating in the blood. The condition is fairly common and is found in about 2 percent of women and 0.2 percent of men. Hypothyroidism affects 10 percent of older adults and involves a deficiency of thyroid hormones. Clinical depression can sometimes be caused by hypothyroidism, an example of which is Hashimoto's thyroiditis.
Our patients on thyroid treatment plans are regularly monitored for healthy thyroid function and control of appropriate thyroid levels.
Melatonin is a compound that occurs naturally in the human body. Its levels in the human body rise and fall over the course of the day, in accordance with circadian rhythms and other biological processes within the body. In the evenings, melatonin levels increase and often help people fall asleep, which is why the hormone is commonly used to overcome insomnia or recover from jet-lag.
Melatonin exerts its power by activating melatonin receptors. It also acts as a potent antioxidant that protects cell DNA. Melatonin secretions are regulated by light rhythms and occur in the pineal gland of the brain. Other cells in the body also produce melatonin, including bone marrow cells, lymphocytes and epithelial cells. The melatonin in these cells is not regulated by daylight cycles and is more highly concentrated among these cells than in the blood.
In the United States, melatonin is sold over the counter as a dietary supplement, to address falling levels of melatonin production, which happens as the body ages. We frequently prescribe melatonin supplements for patients starting at age 40, with increasing dosages as one grows older. Melatonin supplements should be taken once daily at bedtime.
Growth hormones (GH) stimulate growth, cell reproduction and regeneration, both in humans and other animals. There are two types of GH - somatotropin, which is produced naturally in animals, and somatropin, which is created through recombinant DNA technology. Replacement therapy uses the latter.
Produced by the somatotroph cells in the pituitary gland, human growth hormones (hGH) are released into the blood in spurts during deep sleep. When it reaches the bloodstream, hGH stimulates the liver to produce “insulin-like growth factor I” (IGF-I). Because hGH is released in spurts, it is difficult to measure accurately at any given time. Instead, IGF-I levels, which are more constant, are used as a gauge for hGH production.
An interesting historical fact behind hGH is that its application for anti-aging treatment began when the hormone was being studied for dwarfism and pituitary trauma. These are diseases or conditions in which hGH production is greatly reduced or non-existent. To treat these disease states, the human growth hormone was replaced in the patients, but only until growth was achieved.
At the time of the research, replacement hormones for hGH were obtained from human cadavers until 1986, when new advances in recombinant DNA enabled the mass production of pure, uncontaminated hGH using bacteria. The availability of large amounts of hormone for research led to further study into hGH beyond just its growth roles, to include physiologic functions.
Many patients who were treated with hGH for dwarfism or pituitary trauma experienced several medical problems once they stopped taking hGH treatment. In essence, they found themselves aging prematurely, with twice the risk of heart disease, increased abdominal fat, lower muscle mass, depression, social isolation and poor professional performance. A Swedish study on these patients, however, discovered that a single year of hGH treatment successfully reversed all of the effects of premature aging. The results eventually caused the FDA to approve hGH replacement therapy in August 1996 to treat growth hormone-deficient adults (GHDA).
Concurrently in Wisconsin, another scientist was also exploring the biologic effects of hGH. He documented the continuous decline in growth hormone secretions starting around 30 years of age and sought to correlate this decline with changes in body composition. By 1990, the scientist had published his findings in the New England Journal of Medicine - hGH replacement showed enormous age-reversing effects in 21 men, age 61 to 81. Following six months of therapy, study subjects acquired an average of 8.8% lean body mass and lost 14% fat mass; increased their skin thickness by 7% (skin becomes thinner and less elastic with age); increased their bone density by 1.4%; and reported an enhanced sense of overall well-being. Rudman characterized these impacts as “equivalent in magnitude to the changes incurred during 10 to 20 years of aging.”
The landmark study sparked substantial interest in hGH as an anti-aging therapy, inspiring nine new clinical trials by the National Institutes of Health to test the effect of hGH replacement therapy on healthy adults above age 65. These trials had substantial implications, recognizing that some 40% of adults over 60 have the same IGF-I levels as children with stunted growth or people with pituitary damage.
As with all aspects of science, however, debates continue today about the practice of physiological manipulation. Some opportunistic groups and individuals have also misused and falsely advertised their products, particularly when they stand to profit financially. However, leading experts in the field of anti-aging therapy continue to consider hGH a vital part of adult hormonal therapy and one of the most valuable tools we have to help people live longer, healthier lives.
What to Expect from hGH Therapy
Every patient may have different levels of IGF-I, which is the primary indicator for hGH secretion in your body. Depending on your starting level of IGF-I, our physicians will prescribe the appropriate dosages needed to achieve optimal levels in your body (350 to 400 ng/ml). Most people above age 35 will have reduced levels of IGF-I and may benefit from supplementation.
While every patient’s experience will vary, the benefits you can expect from hGH therapy include:
- Decreased fat mass by 10 to 14 percent after approximately 6 months (predominantly around the waist) without any change in diet and exercise
- Increased lean muscle mass of approximately 7 to 10 percent in the first six months of therapy
- Improved bone density after one year of therapy. Percentage increase depends on starting levels of hormone
- Improved cardiac and lung function, lowered blood pressure
- Increased physical and mental energy
- Increased skin hydration and less propensity for developing wrinkles
- Accelerated wound healing
- Increased immune system functioning, including thymus regrowth (critical to the function of T-cells)
- Decreased total and LDL cholesterol levels, and increased HDL levels
- Improved sleep
- improved vision
- Improved mood
The more severe your starting deficiency of growth hormones (below 100 ng/ml, for example), the more significant changes you will see in your body composition in the first six months of treatment. If you have a mild deficiency of growth hormones to start with, the treatment will serve to prevent the onset of age-related changes.
Safety of hGH Replacement Therapy
A great deal of evidence exists today affirming the safety of growth hormone replacement therapy in adults with deficiencies in growth hormones, which led the FDA to approve hGH for treatment. As normal healthy adults share similar body compositions as GHDA, we believe hGH treatment, with careful and appropriate dosages, are safely applicable for non-GHDA as well. Without a doubt, hGH use has been abused by many, which unfortunately has generated unfounded fear and misinformation about the therapy program. However, not one of the long-term growth hormone replacement studies by the NIH was halted due to adverse effects. Data suggests no adverse effects in GHDA who have used the therapy for a decade, nor does any evidence suggest that long-term use of hGH can increase the risk of cancer.
“When one does not abuse or overdose human growth hormone, there is simply no evidence suggesting that human growth hormone replacement therapy causes any long term side effects,” according to Dr. Bengtsson, a leading expert in the field, (Hormone Research, 43, p 93-99, 1995). Still, cancer patients should not take growth hormones, as they may worsen the disease. At Youth Diagnostics™, we screen patients for cancer regularly.
The Problem of Dose
Many different sources may offer conflicting and contradictory evidence about the benefits or negative effects of hGH. One study involving older men documented a high incidence of side effects. However, these men were taking hGH doses that exceeded the amounts needed to achieve positive changes. The study subjects also took the dosages only three times a week, whereas new research indicates that hGH injections should be administered 1-2 times daily, using lower dosages than those used in the study. At this rate and dosage level, no significant side effects occur. Patients may experience swelling or aching in the joints for a few days during the early period of therapy.
No other hormone has demonstrated the ability to achieve the kinds of positive changes that hGH can generate. But growth hormones may not be for everybody. hGH therapy can be expensive (approximately $400 to $800 per month). Others may be uncomfortable with injections, which are the only safe and effective method for administering the hormone, and must be done in small doses each day. We encourage our patients to avoid any offers of non-injectable or hGH stimulators that are available online and over the counter.