Bio-identical Hormone Replacement Therapy
Clinically Speaking
Hormone replacement therapy (HRT) is commonly used to treat menopausal symptoms such as hot flashes, vaginal dryness, mood swings, sleep disorders, decreased libido, and an increased risk of fractures due to osteoporosis. Hormones used in HRT include estrogen and progestin (a synthetic progesterone). Some women, usually those who have had their uterus removed, received estrogen-only therapy. Common example of HRT therapy include Premarin®, Climara®, Estraderm®, Provera®, Prempro®, and Activella®.
Until recently, HRT was thought to reduce the risk of heart disease and bone fractures caused by osteoporosis, in addition to treating common menopausal symptoms. In the early 1990s, a group of investigators conducted a study known as the Women’s Health Initiative (WHI), to identify the benefits and risks of HRT, specifically estrogen with or without progesterone. They found that HRT replacement did in fact decrease the incidence of colon cancer and fractures in those without a diagnosis of osteoporosis and improved menopausal symptoms. However; there was an increased incidence of thromboembolic disease, breast cancer, coronary artery disease, and strokes. The study was prematurely terminated and the investigators concluded that the risks of HRT outweigh the benefits. Soon after that, the Heart Estrogen/progestin Replacement Study (HERS) confirmed the WHI’s findings and concluded that HRT had no protection against CAD. Both studies used synthetic estrogen and progestin hormones.
The WHI study raised several safety concerns regarding the use of synthetic hormones in HRT. As a result, the use of hormones that are structurally identical to those found in the body has seen a steady increase. Also, since the end of the WHI study, Premarin® and Prempro® (equine estrogen and synthetic progestin) sales revenues have dropped over 30%. These hormones that are structurally identical to those found in the body are known as “bio-identical” hormones. Many believe that “bio-identical” hormones have fewer side effects than the synthetic hormones. The synthetic hormones contain side chains that alter their chemical structure in relation to hormones found in the body. The goals of Bio-identical Hormone Replacement Therapy (BHRT) include relief from symptoms due to decreasing hormone production, protection from conditions that natural hormones usually protect against, and the establishment of hormonal balance. The hormones are primarily derived from the yam and soybean plants before being altered in the lab to create the bio-identical hormones. The term “bio-identical” is not recognized by the FDA; however, BHRT has been used for over 40 years in Europe and has been extensively studied. Although the term, “bioidentical”, is not recognized by the FDA; estradiol, progesterone, and testosterone are FDA approved
Hormones commonly used in BHRT include estrogens (estrone, estradiol and estriol), progesterone, and androgens. Estrogens are thought to relieve menopausal symptoms, such as vaginal thinning and dryness, depressed mood, poor energy levels, and sleep problems. The normal balance of estrogens in the female body is 10% estrone, 10% estradiol, and 80% estriol, but the actual levels fluctuate. Estrone (E1) is the main estrogen produced in the body after menopause, and is not commonly seen in BHRT. Estradiol (E2) is the most potent of the estrogens and is the primary estrogen produced before the onset of menopause. Estriol (E3) is believed to protect against breast cancer and is produced in higher concentrations during pregnancy. Estriol also alleviates several vaginal and urinary symptoms of menopause.
Premarin® (Wyeth) is a synthetic estrogen product that is extracted from the urine of pregnant mares, and sometimes referred to as conjugated equine estrogens. Premarin® contains estrone and at least 10 other estrogens (some sources claim as much as 100 estrogens) not found in the human body. Estrone comprises 50% of Premarin® which is more than the amount naturally found in the body. Estrogen is given with progesterone unless the patient has had a hysterectomy. Patients that have had a hysterectomy can be given estrogen unopposed although this is not recommended with BHRT therapy since there are progesterone receptors throughout the body. The most common compounded estrogen is Bi-Est. It is comprised of estriol (80%) and estradiol (20%). Tri-Est, which contains all three naturally occurring estrogens, is sometimes used because it is compounded in concentrations naturally found in the body.
Progesterone is another bio-identical hormone used in HRT; however, the term is often applied to synthetic progesterones as well. Synthetic progestins can have serious side effects, while bio-identical progesterones have not been shown to have negative side effects. In general, studies suggest bio-identical progesterone may improve hot flashes, depression, and anxiety related to menopause. Progesterone also balances estrogen dominance; however, studies have not been conducted on bio-identical progesterone to claim efficacy or safety. Regarding BHRT, the American College of Obstetricians and Gynecologists recommends that progesterone be given with estrogen, so that estrogen in the body is not unopposed. Progesterone is sometimes given alone in perimenopause (the period of time before menopause) because progesterone levels begin to drop before those of estrogen. This leads to estrogen dominance which can cause some of the symptoms seen during perimenopause.
Androgens, which include testosterone and DHEA, are also used in BHRT. They play a role in skin, muscle, bone integrity, and libido in both men and women. Testosterone and/or DHEA are sometimes given as a component of BHRT in women due to decreasing levels of testosterone and DHEA that is experienced with increased age. Testosterone is also given to men experiencing andropause also known as male menopause. It is only recommended for men whose testosterone levels are low. Goals for testosterone replacement therapy in men include improving mood, erectile dysfunction, and libido.
Bio-identical hormones are compounded at Wilson Pharmacy. Women usually hear about this option from their physician or from other patients receiving this treatment option. Some patients will contact our pharmacy for information regarding bio-identical hormones. The pharmacist will schedule an appointment and discuss the patient current symptoms, current HRT method (if any), and past medical history. There are saliva and spot blood tests available to help determine hormonal levels, which can be used in along with the patient’s symptoms to develop an individualized BHRT regimen for each patient. The pharmacist also educates the patient about BHRT, and makes it clear that there is not any data on the safety, efficacy or long-term effects of bio-identical hormones. If the patient meets with a pharmacist prior to obtaining a prescription from her physician; the pharmacist will send suggested orders to the patient’s physician before any therapy is started. These recommendations must be signed by the physician before therapy can be initiated with bio-identical hormones.
Most patients are started on Bi-Est, progesterone and testosterone applied topically in a vanishing cream or gel. The three hormones are dispensed to the patient separately so that each hormone can be adjusted as necessary until the patient’s dose is stabilized. The ultimate goal of therapy is to maximize benefits and minimize side effects to the patient. Once this goal is achieved and the final dosage is reached, all hormones can be put into one container or syringe to allow for easier administration. The preferred route of administration is topical but other dosage forms available are oral capsules, troches, and sublingual drops.
The use of bio-identical hormones continues to increase in popularity. The idea of replacing the body’s hormones with identical hormones seems logical although larger studies need to be done on their safety, efficacy, and long-term effects. Larger studies have not been done because bio-identical hormones are compounded primarily by local pharmacies and not large drug manufacturers. Caution must be exercised in prescribing and using bio-identical hormones in hormone replacement therapy as with any other medication.
Wilson Pharmacy, Inc.
Steve Lane, Pharm.D
Director of Pharmacy
Perry Ripple, Pharm.D
Compounding Pharmacist