Criteria for the choice and monitoring of Menopausal Hormone Therapy

Abstract

To review the criteria for the selection of estrogens and especially progestogens for optimizing Menopausal Hormone Therapy (MHT). The main criteria are primarily derived from the Women's Health Initiative (WHI)-trial, disclosing the main risks like endometrial cancer, coronary heart disease (CHD), stroke, venous tromboembolism (VTE) and breast cancer. In addition observational studies must be considered for individualizing MHT, because WHI has tested only one preparation and has a lot of problems like early opening of the hormone/placebo-code (i.e., loss of placebo control), in 60% MHT-initiation too late, and in 40% risk factors for cardiovascular diseases and breast cancer. Pharmacological properties should be considered, such as only oral, but not transdermal estradiol increases VTE-risk. The choice of progestogens could be dependent on the different "partial effects" on steroid receptors, e.g., use of anti-androgenic progestogens in metabolic syndrome, Polycystic Ovary Syndrome (PCOS) etc., taking advantage of the anti-mineralocorticoid effect of drospirenone to stabilize blood pressure and reduce the risk of stroke, selection of tibolone for patients with sexual dysfunctions because its androgenic properties etc. Most important for the selection of the progestogen is endometrial efficacy, primary indication for progestogens in MHT. Therefore regular endometrial monitoring is reommended, using sequential or continuous combined regimens; "hormonal curettage" and/or the progestogen challenge text to avoid endometrial hyperproliferation. Levonorgestrel-IUD as progestogen component can reduce progestogen-dependent risks, offering also contraception, but often with longer bleeding problems, in contrast to sequential regimens of MHT, which can be used to treat irregular bleedings. Other main indications are treatment of climacteric complaints and prevention of osteoporosis and possible other preventive options. Regarding contraindications, according to the general rules of "class-labeling", they are the same for every MHT despite there are differences in benefits and risks. Choice of the timing of MHT-initiation is crucial to whether cardiovascular prevention (early start) or (like in WHI) increased risk of CHD and stroke occurs. The increased risk of breast cancer can be reduced using progesterone or its isomer dydrogesterone. Since, however, this risk cannot been excluded with any MHT, recommendations for screening on the possible development of breast cancer are given, on the basis of own recent research. Criteria for the selection of MHT are mainly to reduce possible risks as seen in WHI since for every MHT efficacy is good and essentially the same. Often the best choice is estradiol combined with progesterone or dydrogesterone, but also other progestogens should be considered including LNG-IUD, to optimize and individualize MHT.

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