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 examples 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 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, estradiol, progesterone, and testosterone are
FDA approved. Moreover, BHRT has been used for over 40 years in Europe and has been extensively studied.
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
Wilson Pharmacy, Inc.
Steve Lane, Pharm.D
Director of Pharmacy
Perry Ripple, Pharm.D