Níveis circulantes de estradiol, estrona e gonadotrofina, após a administraçåo de 17 beta-estradiol ativo por via oral, em mulheres após a menopausa / Circulating estradiol, estrone and gonadotropin levels following the administration of orally active 17 B-estradiol in postmenopausal women

A ingeståo de um único comprimido contendo 2mg de 17 beta-estradiol micronizado (E2) resultou em acentuado aumento das concentraçöes séricas de E2 e estrona (E1), em 9 mulheres após a menopausa. O aumento do E2 circulante se tornou significativo dentro de 2 horas, atingiu o pico (110 pg/ml; 437 por cento de aumento) em 5 horas, e permaneceu significativamente elevado em 8 horas após o tratamento. Em 24 horas, a concentraçåo sérica de E2 nåo diferiu significativamente da básica. Ao contrário, foi observado um aumento mais rápido (dentro de 1 hora) e pronunciado (4 vezes) na concentraçåo sérica de E1. O aumento continuou até ser atingido um pico (467 pg/ml; 2.000 por cento) em 6 horas após o tratamento. A seguir, a concentraçåo sérica de E1 decdlinou progressivamente, mas continuou significativamente elevada (140 pg/ml; P<0,01) em 24 horas após o tratamento. As concentraçöes séricas de FSH e LH se mostraram significativamente reduzidas em 6 e 3 horas, respectivamente, e ambas as gonadotrofinas permaneceram significativamente reduzidas em 24 horas após a ingeståo de E2. As relaçöes de E1:E2 em circulaçåo aqui relatadas (ca.3-6) foram muito superiores às observadas por outros investigadores após a administraçåo endovenosa de E2 (i.e. < 1). Assim, os resultados mostram que o E2 micronizado por via oral é rapidamente absorvido, e que, durante esse processo, uma porçåo significativa do hormômio se converte em E1 no trato gastrintestinal. Além disso, 2 mg de E2 oral exercem significativa atividade biológica, conforme demonstrado pela supressåo de gonadotrofina do soro. (J Clin Endocrinol Metab 40:518, 1975)

Micronized 17 beta-estradiol for oral estrogen therapy in menopausal women.

Micronized 17beta-estradiol (E2) was used as oral replacement therapy in 369 patients with estrogen deficiency and related menopausal symptoms. Over 95 percent of 319 patients evaluable for efficacy gained satisfactory relief of their symptoms from cyclic (on 21 days/off 7 days) E2 therapy. Approximately 77 percent required no adjustment of their initial daily dose, viz, 1 mg (5 or less hot flushes per day) or 2 mg (6 or more flushes daily). In addition, 80 percent (58/72) of the patents who did not obtain adequate control from their starting dose were successfully titrated, either upward to a maximum of 4 mg/day or downward for maintenance. Overall, a higher percentage of patients were treated successfully with 2 mg daily (209/319; 66 percent) than with 1 mg/day (22 percent). About 8 percent of the patients required 3 or 4 mg daily, while 4 percent failed to derive adequate benefit from micronized E2. Oral E2 therapy was well tolerated; hence, the attrition rate due to side effects or lack of control was only 6 percent (22/369). Moreover, all laboratory fingings were within normal limits, even in patients treated with E2 for over 12 months. Coincidental endometrial changes were found in 9 patients, all of whom had received long-term (9 months-3 years) estrogen therapy prior to entering this study. Thus, the stste of the endometrium should be determined before any estrogens are given for the monopause. It is concluded that micronized E2 is highly efficacious, well accepted, and safe for oral estrogen-replacement therapy in menopausal women.

Physiologic significance of 17beta-estradiol binding in the rabbit Fallopian tube.

Rabbit Fallopian tube contractility was recorded in vitro during perfusion with either Locke's solution or that solution containing CN-55, 945-27 (CN; or CI-628), a nonsteroidal estrogen antagonist (Endocrinology 79: 153, 1966). Contractility was inhibited and 17beta-estradiol (E2) displaced from both its cytoplasmic (8S) and nuclear (4S) receptors in the presence of the above agent. These effects result from a direct interaction between CN and the E2-receptor complexes. Two types of evidence show the specificity of the foregoing responses: (1) nonspecific binding of E2 to serum proteins was unaffected by the antagonist and (2) CN had no effect on contractility of a nontarget tissue, i.e., rabbit ileum. In addition, Fallopian tube contractions induced by strong electrical stimulation of K-depolarized tissues (i.e., in the absence of normal ionic gradients) were inhibited by CN and a decrease in the binding capacities of 8S and 4S receptors was again observed. Thus, antagonism of specific E2 binding inhibits the contractile mechanism at a level other than the cell membrane. These observations, and additional findings concerning the reversibility of CN action, indicate that E2 binding is essential for contractility of the rabbit Fallopian tube.

Circulating estradiol, estrone and gonadotropin levels following the administration of orally active 17beta-estradiol in postmenopausal women.

Ingestion of a single tablet containing 2 mg micronized 17beta-estradiol (E-2) produced marked increases in the serum concentrations of E-2 and estrone (E-1) in 9 postmenopausal women. The rise in circulating E-2 became significant within 2 h, reached a maximum (110 pg/ML; 437% increase) at 5 h, and remained significantly elevated at 8 h posttreatment. By 24 h, the serum E-2 concentration was not significantly different than baseline. In contrast, a more rapid (within 1 h) and pronounced (4-fold) increase in the serum concentration of E-1 was observed. This rise continued until a peak (467 pg/ml; 2000%) was reached 6 h posttreatment. Thereafter, the serum E-1 concentration declined progressively but was still significantly elevated (140 pg/ml; P smaller than 0.01) 24 h after treatment. Serum concentrations of FSH AND LH were significantly decreased within 6 and 3 h, respectively and both gonadotropins remained significantly suppressed 24 h following the ingestion of E-2. The ratios of circulating E-1: E-2 reported herein (ca. 3-6) were much higher than those observed by other investigators following iv E-2 (I.E., smaller than 1). Thus the data indicate that micronized E-2 peros is readily absorbed and that during this process a significant portion of the hormone is converted to E-1 by the gstrointestinal tract. In addition, 2 mg oral E-2 exerts significant biologic activity as assessed by serum gonadotropin suppression.