Hormone Replacement Therapy: Does Aging Limit Therapeutic Benefits

Hormone Replacement Therapy: Does Aging Limit Therapeutic Benefits?

Area: medicine (gynecology/menopause)

Ceci Mendes Carvalho Lopes

Professora-Assistente-Doutora Clinica Ginecológica – Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Menopause is a physiologic event, present in normal lives of women. Sometimes, it is uneventful, but sometimes there are many discomforts, symptoms and metabolic alterations following it. Seeking to obtain welfare, women ask for treatment. The first and best recommendations are to observe nutritional care, exercise and mental hygiene. But sometimes it is necessary to prescribe medicines. Because its main characteristic is a very low estrogen dosage, the obvious idea about treatment is to replace this hormone. But, if the woman has an intact uterus, it is necessary to give her some progestogen, also, to protect endometrium, avoiding endometrial hyperplasia and even endometrial cancer. Hormonal therapy promotes a better quality of life, diminishing climacteric symptoms, specially hot sweats, but also acting positively on lipids, bone mass, skin, etc. Nevertheless, there are some questions about adverse effects as breast pain, thromboembolism, cancer, and other. They must be considered, aiming health and welfare of each patient. The randomized placebo-controlled Heart and Estrogen/progestin Replacement Studies (HERS-1 and HERS-2) and Women’s Health Iniciative (WHI) failed to show the main objective of prevention of cardiovascular disease of postmenopausal women under HRT. And showed risk of breast cancer, as well as thromboembolic problems, but less colon cancer and osteoporosis. These studies were reviewed and several biases were discussed. Cardioprotection is indeed a controversial theme, yet, but there are indications that early prescriptions, in the first years of postmenopause, are beneficial. Unquestionably, hormonal therapy is the best choice for vasomotor symptoms, prevent genitourinary atrophy and osteoporosis development, and preserves skin appearance. The duration of this treatment is a permanent question. The idea is to use the minimum dose, for the minimum time it is necessary. But to establish this minimum time, sometimes, is very difficult, because, if the medication is suppressed, the patient returns with the same symptoms, and re-starts the metabolic alterations. The studies mentioned above used conjugated equine estrogens and medroxyprogesterone. The first doubt to solve is: changing the estrogen, or the progestogen, the therapeutic answer will be different? It seems the answer is yes! But there are not, at the moment, long-term studies with new schemes. There are some evidences that medroxyprogesterone, in HERS and WHI trials, used to prevent estrogen-induced endometrial hyperplasia, also attenuates beneficial estrogen actions on the coronary circulation and atherosclerosis, and also promoted increase in breast cancer. Other estrogens, specially 17-β-estradiol (because it is natural, or physiologic), and other progestins could be better. So, it is evident that depending on whether they are progesterone or 19-nortestosterone derivatives, progestins differ in their potency and their ability to exert an estrogenic, antiestrogenic or androgenic effect. Here were described unique characteristics in drospirenone, an analogue of espironolactone, or didrogesterone, a retroprogesterone. The choice of the progestin cause different results over important features, as blood pressure. Hypertention represents a major risk for cardiovascular disease, and often it is inadequately treated. Hormonal treatment may act on aldosterone metabolism. The use of drospirenone, trimegestone or didrogesterone may promote benefits on hypertensive women, even reducing bood pressure. Estrogens by non-oral administration would be better to hypertensive patients, because avoiding passing through the liver first of going to the rest of circulation, do not stimulate the same way the aldosterone-renin-angiotensin system. Other questions, as lipid metabolism (better with hormonal treatment), coagulation (controversial, but if the estrogen chosen is estradiol, the natural estrogen, it seems the risk is alike the risk during reproductive years), skin aspect (acne, hirsutism), or weight gain (sometimes diminishing weight), breast pain, headache, and genital bleeding, must be considered and studied individually. Indeed, hormonal treatment promotes a best quality of life. There are other therapeutic schemes, without hormones, but sometimes they need two or more different medications, each one for treat a different problem. Or the treatments are unsatisfactory because do not promote the desired relief. So, each patient is unique, and must be considered individually. The therapeutic scheme, and the duration of it, must be decided one by one, aiming the best for each one. And, if the treatment is beneficial, the time it will be a good choice is undefined.