It has been suggested by some that the absence of significant effect in some of these studies could be due to selective prescription to overweight women who have higher baseline estrone, or to the very low progesterone serum levels after oral administration leading to a high tumor inactivation rate.Evaluating the response of breast tissue density to HRT using mammography appears to help assessing the degree of breast cancer risk associated with therapy; women with dense or mixed-dense breast tissue have a higher risk of developing breast cancer than those with low density tissue.Micronized progesterone does not appear to be associated with breast cancer risk when used for less than five years with limited data suggesting an increased risk when used for longer duration.A retrospective Cox proportional hazards analysis from Richard Neapolitan endorsed the reduced risk breast cancer with conjugated equine estrogen usage alone, but also suggested that conjugated equine estrogen with medroxyprogesterone acetate was associated with a risk reduction in breast cancer and that bioidentical hormone therapy was not associated with a statistically significant effect. There have been no prospective randomized clinical trials comparing the two routes of administration with regards to breast cancer.For women who previously have had breast cancer, it is recommended to first consider other options for menopausal effects, such as bisphosphonates or selective estrogen receptor modulators (SERMs) for osteoporosis, cholesterol-lowering agents and aspirin for cardiovascular disease, and vaginal estrogen for local symptoms. Observational studies of systemic HRT after breast cancer are generally reassuring.
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.