Bioidentical hormone therapy is the use of hormones that are identical to those naturally produced by the body. The advantages of this method, as opposed to replacement with synthetic hormones, are numerous. The hormones you receive from bioidentical sources are identical to your own, so they have a complete impact on your body. They act like your hormones would. While synthetic hormones are molecularly similar to your own hormones, they will not have complete action. This inadequate action does not frequently stimulate a proportional hormone reaction in the body. Because synthetics have a different molecular structure than your own hormones, they have the potential to cause different effects on your body.
Smaller doses are needed when using bioidentical hormones as opposed to synthetics because of the “complete action” effect. Bioidentical hormones may come from either plants or animals, but most of them come from plants.
This means that the replacement compounds are better suited to the individual. The symptoms and results of testing are used to create custom doses and combinations of hormones for each patient.
Hormones include more than the well-known estrogen and testosterone. For example, insulin is a hormone that helps regulate growth and is responsible for shuttling glucose from food into cells for energy; your thyroid produces different hormones to help regulate metabolism; and your adrenal glands produce cortisol, known as “the stress hormone,” which, among other things, helps the body store energy from food.
WHAT SYMPTOMS MIGHT I EXPERIENCE IF I HAVE A HORMONAL IMBALANCE?
An imbalance of hormones can cause a variety of problems throughout the body. Hormones can have a lot of different effects on the body, some of which are fatigue, weight gain, hair loss, hot flashes, night sweats, insomnia, and mood swings. During menopause, women may experience any of the following symptoms in addition to others: depression, irritability, insomnia, mood swings, hot flashes, reduced sexual interest, painful intercourse, bloating, panic attacks, hair loss, urinary symptoms, and even infections, headaches, “brain fog,” or memory loss.
WHO SUFFERS FROM HORMONE IMBALANCE?
Hormones are not just for women going through menopause. The menopause is the point in a woman’s life when her ovaries stop producing eggs, and her levels of estrogen and progesterone fall. Symptoms of imbalanced hormones are not just experienced by women going through menopause, but by people of all genders. The process of andropause is similar to menopause in men. Age-related changes in hormones, specifically testosterone, are responsible for this. Age-related changes in hormone levels may cause symptoms such as fatigue, reduced muscle mass, and depression. The rate of decline for testosterone in men is typically more gradual than the rate of decline for estrogen and progesterone in women during menopause. The average rate of testosterone decline for people over the age of 30 is 1% per year.
Adrenal insufficiency, often resulting from a prolonged period of stress, can cause a subsequent decline in sex hormones in both men and women. DHEA is a hormone that is similar to androgens and helps to produce cortisol, which is the stress hormone that is released by the adrenal glands. DHEA also helps support testosterone production. When the adrenals need more DHEA, there is less available to be used in testosterone production, and often men can experience more rapid declines in their testosterone levels than what would be expected from aging alone. While testosterone therapy alone can often treat hormone deficiency in men, it is not always enough to completely address the problem. Preventing testosterone from being converted into estrogen is an important part of treating low testosterone levels in men.
Indications
Hormone replacement therapy is a way to supplement the hormones that a woman loses during the menopausal transition. To reduce the symptoms experienced during menopause, conventional HRT uses a combination of estrogen and progesterone to imitate the hormones produced by the human ovary.
There are many different types of estrogen therapy, including those that come from the human ovary, such as estradiol and estriol. CEE, or conjugated equine estrogen, is the most commonly prescribed estrogen in the United States. Although they have different effects on the human body, both drugs share the same FDA indications, according to the Physicians Desk Reference. [1] [2] [3] The indications for menopausal issues include:
- Treatment of vasomotor symptoms of menopause
- Treatment of genitourinary syndrome of menopause ( previously known as vaginal and vulvar atrophy)
- Prevention of osteoporosis
A progestogen is a substance that is similar to progesterone. Progestins are a type of progestogen. A woman cannot simply have estrogen for HRT if she wishes to protect her uterus from endometrial cancer—she must also take a progestogen with the estrogen. Estrogen alone will cause the endometrial lining to grow. Progestogens stabilize the lining from proliferating abnormally. Although it is commonly assumed that women who have had a hysterectomy no longer need to take progestin, this is not always the case. However, progesterone provides symptom relief from sleep disturbance and mood instability and increasing evidence supports that it offers tissue protection to the breast. [4] [5] [6]
FDA-approved indications for progestogens include:
- Amenorrhea, either primary or secondary
- Assisted reproductive technology treatment
- Endometrial hyperplasia
- Dysfunctional uterine bleeding
Contraindications
Contraindications for oral or transdermal estrogen-based therapies include:
- Known, suspected, or history of breast cancer
- Known or suspected history of other estrogen-based cancer, i.e., uterine cancer. Women who have had a hysterectomy and have no remaining evidence of disease are still candidates for HRT
- Active deep venous thrombosis (DVT) or a history of DVT or pulmonary embolism (PE)
- History of blood clotting disorder, the most common being Factor V Leiden mutation carriers
- Active or history of arterial thrombotic diseases such as myocardial infarction or stroke
- Chronic liver disease or dysfunction
- Migraine with aura
This doesn’t apply to estrogen therapies that are based in the vagina, because the amount of estrogen in the blood from this route is very low. The North American Menopause Society (NAMS) has recommended that the black-box warning that applies to conventional HRT not be applied to transvaginal estrogen treatments. This is because transvaginal estrogen treatments are less likely to cause blood clots than other types of hormone therapy.
WHAT DO THE HORMONES DO?
Other hormones in the body help to regulate the function of each hormone. Here is a brief summary of some functions of each:
- Estrogen: increases metabolism, increases insulin sensitivity, improves sleep, regulates body temperature, maintains bone density, relaxes blood vessels, encourages blood vessel growth particularly in the uterine lining, supports production of neurotransmitters such as serotonin
- Progesterone: Modulates the effects of estrogen, helps promote sleep and reduces hot flashes
- Testosterone: supports mood, energy, and self esteem; aids in muscle recovery, increases sex drive
- DHEA: supports testosterone and cortisol manufacturing, thereby increasing muscle mass and improving energy and focus
- Cortisol: your energy hormone! It helps you wake up in the morning and gets the inflammatory cascade going with neurotransmitters like epinephrine in stressful situations (Think: running from a bear!).
Administration
There are many different types of estrogen and progestogen, which can be taken orally or through the skin as a cream, patch, vaginal insert, or subdermal pellet. Each route of administration has unique benefits and risks.
Oral estrogen increases the resistance to activated protein-C, which in turn increases the risk of developing a blood clot. Estradiol also decreases the formation of plaque in the arteries, which can cause heart attacks or strokes.
How transdermal estrogen bypasses the hepatic metabolism to produce activated protein-C resistance is not fully understood, but it is thought that the risk for blood clotting is negated.
Progestin is most commonly taken orally, although a few forms are available in combination with estrogen in patch form. Progesterone that can be taken orally or vaginally is available, even though the vaginal use has not been approved by the FDA.
Although not FDA approved, specialized pharmacies create compounded estrogen and progesterone creams, sublingual troches, and vaginal inserts.
Adverse Effects
However, this data is based on a small number of postmenopausal women who were given higher doses of HRT than what is typically prescribed. The most commonly referenced information on the potential adverse effects of HRT in the US comes from the Women’s Health Initiative (WHI), which is based on a small number of postmenopausal women who were given higher doses of HRT than is typical. [7] [8] [9]
WHI Trial
This trial had many dimensions, including two separate trials where postmenopausal hormone therapy was given to some participants while others were given a placebo, and neither group knew who received which. [10]
The first arm of the study included CEE at a dose of 0. 625 mg per day, in combination with MPA at a dose of 2.5 mg per day. The arm of the study that looked at patients who had hysterectomies in the past and were treated with 0.625 mg of CEE found that…
HRT and the Breast
The arm of the study that looked at the combination of the two drugs was discontinued early because there was an increase in the number of cases of breast cancer that was higher than expected. The arm of the study that only looked at CEE was not discontinued early, and researchers have continued to follow up with patients for 11.8 years. This study found that using CEE for 5 to 9 years is associated with a 23% reduction in breast cancer. In the arm of the study where the patients took CEE, there was a 63% decrease in mortality from breast cancer, and 38% fewer patients died from all causes after breast cancer was diagnosed when compared to the patients who did not take CEE.
Studies that examine evidence from Europe usually use estradiol derivatives rather than CEE, and non-MPA progesterone or progestins. The conclusions from these studies are vastly different and unequal. Estradiol increased the risk of breast cancer by 10%, but estradiol with progesterone decreased the risk of breast by 10%.
HRT and the Heart
In the WHI arm of the CEE/MPA, the number of cases of coronary heart disease increased by 24% over the course of five years. The largest increase in risk was seen in the first year, when the number of cases increased by 81% (HR=1.81). [11] [12] This evidence requires cautious interpretation due to the following:
- The average age of the patient treated in this study was 62 years. In women who started on therapy within ten years of menopause, there was a risk reduction of CAD of 11% (HR=0.89), but this was not statistically significant.
- In those women who continued CEE/MPA for over six years, the risk of CAD dropped by 30% (HR=0.70).
The risks mentioned do not apply to treatments that use estradiol and progesterone. There is evidence from basic science studies that estradiol protects the heart through several mechanisms, as opposed to CEE. Some benefits of this include that it can help stabilize any plaques that might be in the arteries, reducing the thickness of the carotid arteries, and also decreasing the calcium levels in the coronary arteries. There have been many studies since then in Europe and the United States that show that cardiovascular disease and death are reduced when HRT starts within the first four years of the menopause transition. The “Timing Hypothesis” is the theory that you will see a cardiovascular benefit if you start HRT closer to the time of the menopause transition, compared with if you start later.
HRT and Risk of Stroke [13]
There was a 31% increase in strokes in the arm of the WHI trial that was taking CEE/MPA, and a 39% increase in strokes in the arm of the trial that was taking CEE.
The results of studies investigating the link between oral estradiol and stroke risk are conflicting, with some studies showing an increased risk and others showing no change. However, the incidence of fatal stroke does not appear to be affected.
HRT and the Risk of Venous Thromboembolism (VTE)
The rate of VTE was two times higher in the group taking CEE/MPA than the placebo group.
Numerous European studies have found that transdermal estradiol does not pose the same thromboembolic risk. The overall risk of a blood clot from the ESTHER study in France is 0.9, which is a decrease in risk. Other studies looking at different doses and routes of transdermal estradiol have found similar results, with no increase in blood-clotting risk.
HOW ARE HORMONES MONITORED?
Your doctor could opt to monitor your hormone levels via saliva or blood testing. It is preferable to monitor cortisol and estrogen through saliva testing, while some hormones, such as pregnenolone, are best monitored by blood levels. Your doctor will determine how often to test your hormone levels, but it is often done every three months after any changes to your hormone treatment plan.
WHY TREAT HORMONE IMBALANCE?
Some of the reasons to address hormone imbalance are to relieve symptoms of imbalance, improve quality of life, and protect long-term health. Osteoporosis and heart disease can be caused by hormone deficiencies, such as estrogen and progesterone. Certain hormone imbalances, such as estrogen dominance, can increase your risk of certain cancers when left untreated.
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