The findings of numerous studies on hormone replacement therapy (HRT) conflict and, as a result, have raised serious questions regarding the appropriate use of HRT. Hormone replacement is an approved therapy for relief from moderate to severe hot flashes and symptoms of vulvar and vaginal atrophy. Numerous studies have confirmed that estrogen replacement decreases the risk of colon cancer, that estrogen and progesterone decrease fracture risk, and that various hormones increase energy levels and enhance libido. Reputable sources offer conflicting reports regarding issues such as memory, Alzheimer’s disease, and stroke.
Many patients and medical professionals are unaware of the availability of bio-identical alternatives. In reality, women’s experiences and the clinical outcomes of HRT differ vastly depending on the dose, dosage form, route of administration, and–most importantly–whether the hormones are synthetic or bio-identical. As a result of concerns and doubts generated by studies that use synthetic hormones, many women who could substantially benefit from bio-identical hormone replacement may never have the opportunity.
Published research delineating the differences between natural bio-identical and synthetic HRT is now more abundant, but studies of bio-identical HRT will probably never be as plentiful as those dealing with patented synthetic hormones. Our pharmacy welcomes your questions.
The term “estrogens” actually refers to a group of related hormones, each of which has a unique profile of activity. Under normal circumstances, a woman’s circulating estrogen levels fluctuate based on her menstrual cycle. For Hormone Replacement Therapy, these hormones are often prescribed in combination to re-establish a normal physiologic balance. The three main estrogens produced in female humans are:
- Estrone -E1- (10-20% of circulating estrogens) is the primary estrogen produced after menopause.
- Estradiol -E2- (10-30% of circulating estrogens) is the most potent and major secretory product of the ovary and the predominant estrogen produced before menopause.
- Estriol -E3- (60-80% of circulating estrogens) causes little or no buildup of the endometrium and is very effective in alleviating vaginal and urinary symptoms in postmenopausal women. Estriol is produced in very large amounts during pregnancy. High levels of estriol are found in vegetarians and Asian women, who also have a much lower incidence of breast cancer.
“Progesterone” is a term that is incorrectly used interchangeably to describe both natural bio-identical progesterone and synthetic non- bio-identical derivatives. Synthetic progestins (also called progestogens or progestational agents) are analogues of bio-identical progesterone and have been developed because they are patentable, more potent, and have a longer duration. Medroxyprogesterone acetate, the most commonly used synthetic progestin, was shown in a large study to cause significant lowering of HDL “good” cholesterol, thereby decreasing the cardioprotective benefit of estrogen therapy. Bio-identical progesterone has not been reported to produce any serious side effects when administered in physiologic doses. However, progestins can have significant and serious side effects at typical doses, including migraine headache, weight gain, mood swings, depression, irritability, acne, menstrual irregularities, and fluid retention. These side effects are a frequent cause for discontinuation of HRT. Only about 20% of women who start synthetic HRT remain on it two years later.
- Is commonly prescribed for perimenopausal women to counteract “estrogen dominance,” which occurs when a woman produces smaller amounts of progesterone than normal relative to estrogen levels.
- Alone, or combined with estrogen, may improve bone mineral density.
- Minimizes the risk of endometrial cancer in women who are receiving estrogen.
- Is preferred by women who had previously taken synthetic progestins.
- May enhance the beneficial effect of estrogen on lipid and cholesterol profiles and exercise-induced myocardial ischemia in postmenopausal women (in contrast to medroxyprogesterone acetate).
The benefits of progesterone are not limited to the prevention of endometrial cancer in women who are receiving estrogen replacement. Progesterone therapy is not only needed by women who have an “intact uterus,” but is also valuable for women who have had a hysterectomy. Vasomotor flushing is the most bothersome complaint of menopause and is the most common reason women seek HRT and remain compliant. For over 40 years, estrogens have been the mainstay of treatment of hot flashes; but transdermal progesterone cream may be effective, as well. Women who have had postpartum depression once have about a 68% chance of having it again after another pregnancy, but trials using prophylactic progesterone have shown that it is possible to reduce the recurrence rate to 7%. Other benefits include improved bone density and enhanced glucose utilization.
Androgens are hormones that are important to the integrity of skin, muscle, and bone in both males and females and have an important role in maintaining libido. Declines in serum testosterone are associated with hysterectomy, menopause, and age-related gender-independent decreases in DHEA and DHEA-sulfate. DHEA (dehydroepiandrosterone) is an androgen precursor from which the body can derive testosterone. After menopause, a woman’s ovaries continue to produce androgens; however, the majority of the androgens produced in the female body, even before menopause, come from peripheral conversion of DHEA. As the body ages, production of DHEA declines so that, by the time a woman goes through menopause, the production of DHEA is often inadequate. Additionally, ERT may cause relative ovarian and adrenal androgen deficiency, creating a rationale for concurrent physiologic androgen replacement. Recently, attention has turned to the addition of the androgens to a woman’s HRT regimen in order to alleviate recalcitrant menopausal symptoms and further protect against osteoporosis, loss of immune function, obesity, and diabetes.
Androgens, such as testosterone and DHEA:
- Enhance libido
- Enhance bone building (increase calcium retention)
- Provide cardiovascular protection (lower cholesterol)
- Improve energy level and mental alertness
With the exception of the Postmenopausal Estrogen/Progestin Intervention (PEPI) study, major studies have either failed to distinguish among types and dosages of HRT used in the study or examined only the use of synthetic HRT preparations (as in the case of the Women’s Health Initiative). The Women’s Health Initiative (WHI) study was designed to identify the potential risks and benefits of HRT. The estrogen-progestin portion of the clinical trial was stopped in 2002, after results showed that a synthetic hormone combination containing conjugated equine estrogens (CEE) plus medroxyprogesterone acetate (MPA) increased the women’s risks of developing invasive breast cancer, heart disease, stroke, and pulmonary embolism. The data and safety monitoring board concluded that the risks outweighed the evidence of benefit for fractures and colon cancer. Utilizing data from the WHI, researchers later concluded that synthetic CEE plus MPA does not improve mental functioning and may increase the risk of dementia in women over the age of 65. They suggest that these hormones increase the risk of stroke, which is known to increase the risk of dementia. With regard to the risk of dementia, typical HRT users are in their 50s, and the WHI study focused on women aged 65 and over–women who have a higher risk for dementia. The “estrogen-only” portion of the WHI study was halted in March 2004, after analysis of data suggested that synthetic CEE alone had no impact either way on heart disease (the main focus of the study) but may increase the risk of stroke.