Clinical medical practice changed based upon two parallel Womens Health Initiative (WHI) studies of HRT. Prior studies were smaller, and many were of women who electively took hormonal therapy. One portion of the parallel studies followed over 16,000 women for an average of 5.2 years, half of whom took placebo, while the other half took a combination of CEEs and MPA (Prempro). This WHI estrogen-plus-progestin trial was stopped prematurely in 2002 because preliminary results suggested risks of combined CEEs and progestins exceeded their benefits. The first report on the halted WHI estrogen-plus-progestin study came out in July 2002.Initial data from the WHI in 2002 suggested mortality to be lower when HRT was begun earlier, between age 50 to 59, but higher when begun after age 60. In older patients, there was an apparent increased incidence of breast cancer, heart attacks, venous thrombosis, and stroke, although a reduced incidence of colorectal cancer and bone fracture. At the time, The WHI recommended that women with non-surgical menopause take the lowest feasible dose of HRT for the shortest possible time to minimize associated risks. Some of the WHI findings were again found in a larger national study done in the United Kingdom, known as the Million Women Study (MWS). As a result of these findings, the number of women taking HRT dropped precipitously.
Specific types of hormone replacement include:
Estrogens – bioidentical estrogens like estradiol and estriol, animal-derived estrogens like conjugated estrogens (CEEs), and synthetic estrogens like ethinylestradiol
Progestogens – bioidentical progesterone, and progestins (synthetic progestogens) like medroxyprogesterone acetate (MPA), norethisterone, and dydrogesterone
Androgens – bioidentical testosterone and dehydroepiandrosterone (DHEA), and synthetic anabolic steroids like methyltestosterone and nandrolone decanoateTibolone – a synthetic medication available in Europe but not the United States– is more effective than placebo but less effective than combination hormone therapy in postmenopausal women. It may have a decreased risk of breast and colorectal cancer, though conversely it can be associated with vaginal bleeding, endometrial cancer, and increase the risk of stroke in women over age 60 years.Vaginal estrogen can improve local atrophy and dryness, with fewer systemic effects than estrogens delivered by other routes. Sometimes an androgen, generally testosterone, can be added to treat diminished libido. Continuous versus cyclic
Dosage is often varied cyclically to more closely mimic the ovarian hormone cycle, with estrogens taken daily and progestogens taken for about two weeks every month or every other month, a schedule referred to as cyclic or sequentially combined. Alternatively, continuous combined HRT can be given with a constant daily hormonal dosage. Continuous combined HRT is associated with less complex endometrial hyerplasia than cyclic. Impact on breast density appears to be similar in both regimen timings.