Circulating Estradiol, Estrone and Gonadotropin Levels Following the Administration of Orally Active 17β-Estradiol in Postmenopausal Women

Abstract

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.

Suppression of Gonadotropin Secretion in the Hospitalized Postmenopausal Female as an Effect of Acute Critical Illness

“…In the postmenopausal years, plasma FSH and LH concentrations are markedly elevated as a result of the decline in the negative feedback action of ovarian sex ste roid hormones and of inhibin [8,14,15]. Our study, which was carried out on 126 elderly women admitted to an acute geriatric unit, clearly shows that a large number of hospitalized postmenopausal women are characterized by low and even severely depressed gonadotropin levels.…”

Gonadotropin Secretion during Aging in Postmenopausal Women

“…Since the ovarian endocrine activity is reduced dur ing the postmenopause, such selective feedback activity by ova rian inhibin may also be attenuated. The clinical observation that estrogen replacement almost completely suppresses serum LH and not FSH levels in postmenopausal women [20] adds further credence to the notion that inhibin may play a decisive role in the gonadotropin regulation during the postmenopause.…”

“…That gonadotropin levels increase gradually with the onset of the menopause has been frequently reported [1-4, 18, 19], These changes can be explained by the profound decline in the negative feedback action of ovarian sex steroid concentra tions, since replacement of the ovarian steroids restores the gonadotropin levels of PMW to levels comparable with pre menopausal women [1,2,20]. Although the hypergonadotro pic state persists during postmenopause, the results of our study suggest that gonadotropin levels, in particular the LH concentrations, are subject to a drastic decline during chrono logical aging in women, albeit a high variability may exist be tween individuals of similar chronological and gynecological age.…”

Release of 17-Beta-Oestradiol from a Vaginal Ring in Postmenopausal Women: Pharmacokinetic Evaluation

“…Indeed, no seri ous adverse effects were experienced and, moreover, no vaginal cell atrophy was demonstrated. It would seem, therefore, that the vaginal ring used herein provides a steady state release of oestradiol into the pelvic circula tion and thereby obviates the influence of enteric metabo lism, portal absorption, and 'bolus' surges of circulating oestrogen that follow oral dosing [1],…”

“…When oestrogens are administered intravaginally they are readily absorbed, providing a route by which they can enter the pelvic venous (systemic) circulation without first transversing the gut, portal blood system and liver. This form of parenteral oestrogen therapy, therefore, has the advantage of circumventing the metabolic conversion of oestradiol to oestrone observed after oral administra- tion [1,2], This adverse effect of oral administration of oestrogen arises principally as a consequence of the resul tant high systemic oestrogen concentrations which in crease the synthetic activity of the liver and, hence, the hepatic production of several proteins including sex hor mone binding globulin, renin substrate and coagulation factors.…”