Estrogen therapy effectiveness

Genant HK, Lucas J, Weiss S, et al. Low-dose esterified estrogen therapy Effects on bone, plasma estradiol concentrations, endometrium, and lipid concentrations. Estratab/Osteoporosis Study Group. Arch Intern Med 1997 157 2609-2615. 

Genant, H. K., Lucas, J., Weiss, S., Akin, M., Emkey, R., McNaney-Flint, H., Downs, R., Mortola, J., Watts, N., and Yang, H. M. (1997). Low-dose esterified estrogen therapy Effects on bone, plasma estradiol concentrations, endometrium, and lipid levels. Estra-tab/Osteoporosis Study Group. Arch. Intern. Med. 157, 2609-2615. 

FELSON D T, ZHANG Y, HANNMAN M T, KIEL D P, WILSON P W, ANDERSON J J (1993) The effect of postmenopausal estrogen therapy on bone density in elderly women. N Engl J Med. 329 1141-6. 

SUI. Systemic estrogen therapy also carries numerous short- and long-term side effect risks (mastodynia, uterine bleeding, nausea, thromboembolism, cardiac and cerebrovascular ischemic events, and enhanced breast and endometrial cancer risks). If estrogens are to be used in SUI management, only locally-administered products should be used (Table 50-4). 

Some steroid molecules (estrone, estradiol, and estriol) have phenolic hydroxyl in the ring A (Figure 29.12) and therefore, are able to react as free radical scavengers. In 1987, Japanese authors [264,265] showed that all these compounds inhibited iron adriamycin- or iron ADP-ascorbate-dependent phospholipid and liposomal lipid peroxidation. Later on, most attention was drawn to the study of antioxidative properties of estradiol-17(3 (estrogen E2) it has been proposed that E2 antioxidant activity may contribute to cardioprotection observed after estrogen therapy in postmenopausal women. The necessity for the phenolic hydroxyl has been shown by studying the effects of several estrogens on LDL oxidation. It was found [266]... 

A protective lipid profile, with reduction of total cholesterol and LDL and a modest increase in high-density lipoprotein (HDL), has been associated with oral estrogen therapy (Writing Group for the PEPI Trial 1995). This effect, however, has been considered negligible when compared with the benefits traditionally ascribed to estrogens (Marsh et al. 1999). 

Lippman ME, Krueger KA, Eckert S et al. (2001) Indicators of lifetime estrogen exposure effect on breast cancer incidence and interaction with Raloxifene therapy in the multiple outcomes of Raloxifene evaluation study participants. J Clin Oncol 19(12) 3111—3116... 

Klaiber EL, Broverman DM, Vogel W, et al Estrogen therapy for persistant depression in women. Arch Gen Psychiatry 36 550-554, 1979 Klawans HL, Weiner WJ, Nausieda PA The effect of lithium on an animal model of tardive dyskinesia. Prog Neuropsychopharmacol 1 53-60, 1976 Klein DP Delineation of two drug-responsive anxiety syndromes. Psychopharmaco-logia 5 397-408, 1964... 

One of the earliest examples of predicting efficacy has come from studies of breast cancer, where anti-estrogen therapy is clearly effective in patients whose tumors express the estrogen receptor, and ineffective when no such receptors are present. However, even in this well-studied case, current consensus statements recognize an intermediate endocrine response uncertain state, where the exact boundary between endocrine responsive and endocrine response uncertain is undecided, and may well be different in different clinical settings (19). 

Progestins antagonize estrogen s effects on LDL and HDL to a variable extent. However, one large study has shown that the addition of a progestin to estrogen replacement therapy does not influence the cardiovascular risk. 

Nausea and breast tenderness are common and can be minimized by using the smallest effective dose of estrogen. Hyperpigmentation also occurs. Estrogen therapy is associated with an increase in frequency of migraine headaches as well as cholestasis, gallbladder disease, and hypertension. 

Pinggera G-M, Feuchtner G, Frauscher F, Rehder P, Strasser H, Bartsch G, Herwig R. Effects of local estrogen therapy on recurrent urinary tract infections in young females under oral contraceptives. Eur Urol 2005 47 243-9. 

Estrogen replacement therapy was until recently widely recommended for the prevention of osteoporosis in middle-aged and older women (1). Long-term estrogen therapy also reduces the incidence of ischemic heart disease in such women (2). However, it has always been difficult to know in which women such prophylactic use is likely to be needed, and this dilemma is compounded by the prospect of adverse reactions, which can include any of the acute effects listed in the estrogen monograph, but also in some cases long-term effects such as tumors. 

Teede HJ, Liang YL, Kotsopoulos D, Zoungas S, Craven R, McGrath BP. Placebo-controlled trial of transdermal estrogen therapy alone in postmenopausal women effects on arterial compliance and endothelial function. Climacteric 2002 5(2) 160-9. 

Because raloxifene acts as an estrogen receptor antagonist on some genitourinary tissues, one might expect it to block the vaginal effects of local estrogen therapy. A multicenter placebo-controlled US study in 91 post-meno-pausal women set out to determine whether oral raloxifene (60 mg/day), such as is used to counter post-... 

Despite the still uncertain adverse effects profile of tibolone, it continues to be used in relieving the hot flushes caused by anti-estrogen therapy, and does so in doses that cause no additional problems. In a further double-blind, placebo-controlled study of oral tibolone 2.5 mg/day in 70 postmenopausal women taking tamoxifen after breast cancer surgery tibolone reduced the severity of hot flushes and perhaps also their incidence (3). 

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