Optimizing menopausal hormone therapy: for treatment and prevention, menstrual regulation, and reduction of possible risks

Abstract

Menopausal hormone therapy (MHT) is used to treat menopausal complaints including the genitourinary syndrome of menopause, to prevent osteoporosis, and to treat bleeding problems. Since these can be the indications also in young women, especially with POI (premature ovarian insufficiency) or with surgical menopause (bilateral oophorectomy), also the old term “Hormone Replacement Therapy (HRT)” is still used. The effective component is the estrogen component without relevant difference in the efficacy of the various MHT-preparations. Additional preventive benefits are reduction of cardiovascular disease (including prevention of diabetes mellitus and metabolic syndrome), reduction of colon cancer, and perhaps also Alzheimer's disease, if started within a “window of opportunity”, i.e. in perimenopause or within 6–10 years after menopause.

Primary indication for progestogen addition is to avoid the development of estrogen-dependent endometrial cancer, i.e. addition not recommended in hysterectomized women. Two main schedules, sequential- or continuous-combined estrogen/progestogen regimens, are used for treatment of bleeding problems. For this and for optimizing menstrual regulation detailed recommendations are given including proposed dosages for the available different progestogens if added to oral or transdermal estradiol in different estrogen dosages.

The WHI-study demonstrated the main risks using MHT within a “worst-case scenario”, i.e. start of MHT in old women with high risk for breast cancer and cardiovascular diseases, whereby only “conjugated equine estrogens” and “medroxprogesterone acetate” have been tested. One main result was that the progestogen component is decisive for the risk of breast cancer, which according to own experimental research and observational studies may be reduced using the physiological progesterone or its isomer dydrogesterone. In addition we propose to push forward research for screening patients with increased breast cancer risk like we have done in the past decade demonstrating that certain membrane-bound receptors in breast cancer tissue or blood can increase this risk. To reduce the risk of venous thromboembolism and stroke, transdermal estradiol (gels, patches,) should be used, in free combination with progesterone or dydrogesterone as “golden standard” in patients with increased risk. To increase the compliance in our patients without special risks we mostly use the available fix-combinations of estradiol/dydrogesterone getting strong efficacy, good menstrual regulation or amenorrhea, respectively, but also other combinations may be indicated to take advantage of for example androgenic or antiandrogenic progestogens.