Wide L, Naessén T, Phillips D J
Department of Clinical Chemistry, University Hospital, Uppsala, Sweden.
Clin Endocrinol (Oxf). 1995 Jan;42(1):59-64. doi: 10.1111/j.1365-2265.1995.tb02599.x.
Chronic treatment with 17 beta-oestradiol (E2) implants has been found to counteract the formation of more acidic isoforms of the gonadotrophins in post-menopausal women. Oral medication with an oestrogen in combination with a progestagen is a common hormone replacement therapy (HRT) in post-menopausal women. The present study investigated the effect of such a therapy on the concentration and charge of the gonadotrophin isoforms in serum.
Serum samples were obtained from 20 post-menopausal women, mean age 60 years (range 50-72 years), treated with continuous daily oral medication of 2 mg E2 combined with 1 mg norethisterone acetate (NETA). FSH, LH and E2 in the serum was measured with fluoroimmunoassays. The median charge and charge heterogeneity of the FSH and LH isoforms were determined for each serum by electrophoresis in 0.1% agarose suspension. Sera from 20 post-menopausal women without a history of HRT served as controls. The results were compared with those from previous studies on post-menopausal women treated with E2 implants and on women with normal menstrual cycles.
The E2 level in the oral-E2 + NETA treated women was 198-610 pmol/l, within the range expected during the mid-luteal phase of the normal menstrual cycle and similar to that of the group of women with an E2 implant. The mean LH level was similar to that of the luteal phase of the cycle and significantly lower than that of the controls (P < 0.001), the E2 implant group (P < 0.001) and at the follicular phase of the cycle (P < 0.01). The mean FSH level was similar to that of the follicular phase and the E2 implant group but lower than that of the controls (P < 0.001) and higher than at the luteal phase of the cycle (P < 0.01). The mean values for median charge of both FSH and LH were less acidic than those of the controls (P < 0.001) but more acidic than those for the E2 implant group (P < 0.01; P < 0.001) and for different phases of the menstrual cycle (P < 0.05; P < 0.001). The mean degree of charge heterogeneity of FSH was larger (P < 0.01), while that of LH was smaller (P < 0.01), than for the controls. The mean concentrations of SHBG in the oral E2 + NETA group, the E2 implant group and the controls were similar.
Chronic oral therapy with 2 mg 17 beta-oestradiol combined with 1 mg norethisterone in post-menopausal women efficiently decreased the serum gonadotrophin levels but only partly counteracted the formation of the more acidic isoforms of FSH and LH after menopause. The differences in the charge for both FSH and LH between the E2 implant and the oral E2 + NETA treated groups may be due to the differences in route of administration of E2 or to the effect of norethisterone or both.
已发现用17β-雌二醇（E2）植入物进行长期治疗可对抗绝经后女性促性腺激素更酸性异构体的形成。雌激素与孕激素联合口服给药是绝经后女性常见的激素替代疗法（HRT）。本研究调查了这种疗法对血清中促性腺激素异构体浓度和电荷的影响。
从20名绝经后女性中获取血清样本，这些女性平均年龄60岁（范围50 - 72岁），接受每日2毫克E2与1毫克醋酸炔诺酮（NETA）的连续口服治疗。用荧光免疫分析法测定血清中的促卵泡激素（FSH）、促黄体生成素（LH）和E2。通过在0.1%琼脂糖悬浮液中进行电泳，测定每份血清中FSH和LH异构体的中位电荷和电荷异质性。20名无HRT病史的绝经后女性的血清作为对照。将结果与先前关于用E2植入物治疗的绝经后女性以及月经周期正常女性的研究结果进行比较。
口服E2 + NETA治疗的女性中E2水平为198 - 610 pmol/l，在正常月经周期黄体中期预期范围内，且与E2植入物组女性相似。平均LH水平与周期黄体期相似，显著低于对照组（P < 0.001）、E2植入物组（P < 0.001）以及周期卵泡期（P < 0.01）。平均FSH水平与卵泡期和E2植入物组相似，但低于对照组（P < 0.001）且高于周期黄体期（P < 0.01）。FSH和LH的中位电荷平均值均比对照组的酸性弱（P < 0.001），但比E2植入物组的酸性强（P < 0.01；P < 0.001），且与月经周期不同阶段相比也更强（P < 0.05；P < 0.001）。FSH的电荷异质性平均程度比对照组大（P < 0.01），而LH的电荷异质性平均程度比对照组小（P < 0.01）。口服E2 + NETA组、E2植入物组和对照组中，性激素结合球蛋白（SHBG）的平均浓度相似。
绝经后女性长期口服2毫克17β-雌二醇与1毫克炔诺酮可有效降低血清促性腺激素水平，但仅部分对抗绝经后FSH和LH更酸性异构体的形成。E2植入物组与口服E2 + NETA治疗组之间FSH和LH电荷的差异可能是由于E2给药途径的差异、炔诺酮的作用或两者共同作用所致。
