Strecker J R, Lauritzen C, Goessens L
Maturitas. 1979 Feb;1(3):183-90. doi: 10.1016/0378-5122(79)90007-0.
In 55 patients after oophorectomy and 20 women after natural menopause an oral estrogen replacement therapy was performed with estrone-sulfate, estradiol 17-valerate, estriol-succinate, a combination of micronized estradiol and estriol (Estrifam, Trisequens), and natural conjugated estrogens. In 4 patients a 3 mg estradiol per 5 g ointment substance was applied on the abdominal skin. The interindividual variations of estrogen increments during therapy were considerably high. Oral intake of 2 mg estriol-succinate daily was followed by a 500% increase of total (conjugated + unconjugated) estriol. Concentrations of unconjugated estrogens were not altered by this dosage. Following oral application of the other above mentioned preparations, prominent rises--especially of unconjugated estrogens in plasma--were noted. The concentration peaks occurred within 3--6 h after application. Unconjugated estradiol-17 beta in plasma was comparable with values of the follicular phase of a normal menstrual cycle, unconjugated estrone, however, was nonphysiologically high. Consequently, the E1/E2 ratio was greater than one whereas it is normally below one. 12 h after oral estrogen application, plasma estrogens dropped to almost initial values, so that a second medication seems to be necessary in order to guarantee an adequate supplementation over the course of the day. The hormone values determined in this study did not show significant differences between patients after a natural menopause and after oophorectomy. There was a positive correlation between rising estrogen levels and suppressed gonadotrophins during replacement therapy. The occurrence of climacteric symptoms did not exclusively depend on low estrogen and high gonadotrophin levels. Good tolerance of estrogen therapy with significantly elevated estrogen concentrations in plasma can be obtained transcutaneously in the form of estrogen ointments. Such therapy might simulate the physiological estrogen pattern even better than oral application does because of delayed and diluted steroid flow to the liver.
对55例卵巢切除术后患者及20例自然绝经后女性采用硫酸雌酮、戊酸雌二醇、琥珀酸雌三醇、微粒化雌二醇与雌三醇的组合制剂（Estrifam、Trisequens）以及天然结合雌激素进行口服雌激素替代治疗。4例患者在腹部皮肤涂抹每5g膏体含3mg雌二醇的药膏。治疗期间雌激素增量的个体间差异相当大。每日口服2mg琥珀酸雌三醇后，总（结合型+非结合型）雌三醇增加500%。该剂量未改变非结合型雌激素的浓度。口服上述其他制剂后，观察到显著升高，尤其是血浆中非结合型雌激素。给药后3 - 6小时出现浓度峰值。血浆中非结合型β-雌二醇与正常月经周期卵泡期的值相当，然而，非结合型雌酮却高于生理水平。因此，E1/E2比值大于1，而正常情况下该比值低于1。口服雌激素12小时后，血浆雌激素降至几乎初始值，因此为保证一天内有足够的补充似乎需要再次用药。本研究测定的激素值在自然绝经后患者和卵巢切除术后患者之间未显示出显著差异。替代治疗期间雌激素水平升高与促性腺激素受抑制之间存在正相关。更年期症状的出现并非仅取决于低雌激素和高促性腺激素水平。以雌激素药膏经皮给药可在血浆雌激素浓度显著升高的情况下获得良好的雌激素治疗耐受性。由于类固醇流入肝脏的过程延迟且稀释，这种治疗可能比口服给药更能模拟生理雌激素模式。
