Progestogens endometrial cancer

In the same way as estrogens, progestogens are used in the treatment of several other conditions such as infertility, endometriosis, in the management of certain breast and endometrial cancers, and either alone or in combination with estrogens in the treatment of menstrual disorders, among others. The therapeutic doses required in the treatment of many of these diseases are often significantly larger than those employed in contraception. 

With regard to hormone use in the adjuvant setting a systematic review in the Cochrane database of six trials involving 4351 women concluded Current evidence does not support the use of adjuvant progestogen therapy in the primary treatment of endometrial cancer (see Martin-Hirsch et al., 1999). 

Suggestive case histories raised at an early phase the notion of a possible correlation of oral contraceptives with endometrial cancer. Among cases of endometrial cancer there seemed to be an excess of users of oral contraceptives, particularly of the early high-dose estrogen type. With the virtual demise of these early products, the situation seems to have reversed a 1983 study from the Centers for Disease Control (CDC) in Atlanta showed that women who had used fixed combinations for oral contraception at some time in their lives had a relative risk of endometrial cancer of only 0.5 compared with never-users (112). The protective effect occurred only in women who had used oral contraception for at least 12 months, and lasted for at least 10 years after withdrawal. The WHO adopted the same view in 1988 in the light of multinational data (113). As in the case of hormonal replacement therapy, the protective effect seems to be due to the progestogen component. 

It has long been considered that the risk of endometrial carcinoma may be somewhat reduced by HRT, but that the risk is affected by the dose of progestogen used, if any. In a recent population-based case-control study covering 647 cases and 1209 controls, users of estrogen + medroxyprogesterone acetate (MPA) given for 10-24 days monthly in a dose of 100 mg/month or more showed the same risk of endometrial cancer as women not using HRT... 

However, the relative risk was only 0.8 (95% Cl 0.5-1.5) in those who used a lower monthly MPA dose. Among users of a continuous combined hormone regimen, the risk of endometrial cancer was low relative to untreated women, regardless of the MPA dose. These findings hardly suggest that the dose of progestogen has very much effect on the risk of endometrial cancer. 

Tibolone has combined estrogenic, progestogenic, and androgenic activity. Its effects depend on metabolism and activation in peripheral tissues. Tibolone has beneficial effects on mood and hbido and improves menopausal symptoms and vaginal atrophy. It protects against bone loss and reduces the risk of vertebral fractures. It reduces total cholesterol, triglyceride, lipoprotein (a), and, unfortunately, high-density lipoprotein concentrations. It may increase cardiovascular risk, breast cancer risk, and endometrial cancer risk. 

Oestrogen inhibits the age-related loss of bone that occurs in most women after menopause. Observational studies have indicated that the use of oestrogen reduces the risk of vertebral fracture by approximately 50% and the risk of hip fracture by 25-30%. Unopposed oestrogen increases by 10-fold the risk of endometrial cancer, which is diminished by added progestogen. Therefore combinations of oestrogen and progestogen are the mainstay of treatment for postmenopausal osteoporosis they inhibit the rapid bone loss that occurs immediately after the menopause and should be continued for 5 years. 

Endometrial cancer In an unusually large investigation into the incidence of endometrial cancer as a complication of various forms of HRT in Finland, using data from the country s Cancer Registry and Medical Reimbursement system, all postmenopausal women who during the years 1994—2006 had been treated with HRT for at least 6 months were identified and compared with the general population [27 ]. Continuous estradiol -b progestogen therapy for 3 years or more was associated with... 

Glucocorticoids have inhibitory (apoptotic) effects on lymphocyte proliferation and are used to treat leukemias and lymphomas. Estrogens (fosfestrol) are used to block the effect of androgens in prostate cancer. Progestogens (megestrol, medroxyprogesteroneacetate) have been useful for treating endometrial carcinoma, renal tumors, and breast cancer. 

In women who have not undergone hysterectomy, a progestogen should be added because estrogen monotherapy is associated with endometrial hyperplasia and cancer. 

Megestrol acetate Synthetic progestogen Treatment of endometrial carcinoma and some forms of breast cancer... 

In women with an intact uterus a progestogen should be added to reduce the risk of endometrial hyperplasia and possible transformation to cancer. However, the addition of a progestogen should be weighed against the increased risk of breast cancer associated with its use. 

---