Comparison of pharmacokinetic profiles of a 17β-estradiol gel 0.6 mg/g (Gelestra) with a transdermal delivery system (Estraderm TTS 50) in postmenopausal women at steady state

Objectives: to compare the patterns of a 17β-estradiol (E₂) gel containing 0.6 mg/g (1.5 mg E₂ per day, Gelestra); with the transdermal delivery system (Estraderm TTS 50) applied every 3 days over a 14-day period to women in spontaneous or surgical menopause. Methods: a single centre, open, randomised, parallel-group study was conducted. A total number of 33 postmenopausal women were enrolled. In 23 of them the menopause occurred spontaneously, while 10 women were bilaterally ovariectomized. Randomly, the subjects were treated with Estraderm TTS 50 (no. 8) or with Gelestra (no. 14). The pharmacokinetic study of the drugs was performed at the seventh, ninth and 14th day in Gelestra treated women and at the first, third and second day in Estraderm TTS 50 treated women. In fact, the seventh, ninth and 14th day of percutaneous treatment corresponds to the first, third and second day of application of the transdermal system application. Blood samples were taken by each subject at baseline and 1, 2, 3, 4, 8, 12 and 24 h after the gel or transdermal system application. In almost all samples the level of E₂ and estrone (E₁) were evaluated. Statistical analysis was performed by comparing the two groups of treatment. The following parameters were assessed: mean E₂ and E₁ concentrations, E₂ peak serum concentration within interval from 0 to 72 h (C_max), E₂ trough concentration within interval from 0 to 72 h (C_min), area under the E₂ time concentration curve in the interval from 0 to 72 h (AUC_(0–72)), the average E₂ concentration during the measurement interval, calculated by dividing AUC_(0–72) by 72 h (C_av), E₁/E₂ ratio, and percentage fluctuation (%Fluct) which is equal to 100 (C_max−C_min/C_max). Results: there was no significant difference in E₂ C_av between the two treatments. However, significant differences in favour to the gel on the first day (first h) and on third day (72nd h) and in favour to the patch at the second day (48th h) were detected. C_max, E₁/E₂ ratio and AUC_(0–72) were not statistically different, while a significantly higher C_min for the gel was observed. Furthermore, the 90% confidence interval for AUC_(0–72) ratio (0.83–1.10) was within the commonly applied bioequivalence acceptance range (0.80–1.25). The %Fluct was significantly lower for Gelestra than for Estraderm TTS 50. Conclusions: although the mean E₂ and E₁concentrations, C_max, E₁/E₂ ratio and the AUC_(0–72) did not differ between the two E₂ treatments, the Gelestra treatment showed a lower day-to-day variation over the three day application, than the Estraderm TTS 50.     

A group-comparative study of effects of Ovestin cream versus premarin cream in post-menopausal women with vaginal atrophy

Fourteen post-menopausal women with vaginal atrophy applied, intravaginally, Ovestin® cream (0.5 mg oestradiol/day; 7 patients) or Premarin® cream (1.25 mg conjugated oestrogens/day; 7 patients) for 3 wk. Effects on plasma E₁, E₂, E3, FSH, LH, PRL, TRH-stimulated PRL release, SHBG, and on maturation value (MV), ferning (F) and spinnbarkeit (S) were studied. Endometrial biopsies at pre-treatment and at 2 wk were obtained from 2 patients from each group.

Premarin induced a significant and progressive rise in E₁ and E₂ levels and in SHBG, whereas Ovestin induced no changes. Both creams increased E₃ slightly and suppressed FSH and LH, Premarin suppression of FSH and LH being significantly greater. No significant changes in PRL or TRH-stimulated PRL release occurred with either cream. A similar, marked rise in the MV occurred, but the effect of Premarin on F and S was significantly greater. Endometrium remained atrophic in the 2 Ovestin-treated patients, but moderate proliferation occurred in the 2 Premarin-treated patients. The data showed Ovestin cream to be superior to Premarin cream because of the absence of undesirable effects on E₁ and E₂ levels and the subsequent changes in SHBG and endometrium.     

Effects of treatment with amphetamine and diazepam on Mycobacterium bovis-induced infection in hamsters

Tuberculosis is an example of an infection with an intracellular bacterium in which sensitivity is determined mainly by the host response. Macrophages are the architectural and functional units of the granulomas described in tuberculosis. Treatment with amphetamine (AMPH) and diazepam has been reported to decrease macrophage activity The present experiment was undertaken to investigate the effects of AMPH and/or diazepam given alone or in combination on hamster resistance to Mycobacterium bovis. The effects of these treatments on serum Cortisol levels were also studied. Adult hamsters were treated i.p. with AMPH (group E₁ = 1.0 or 2.0 mg/kg/day), with AMPH (group E₂ = 1.0 or 2.0 mg/kg/day) plus diazepam (2.0 mg/kg/day), with diazepam (group E3 = 2.0 mg/kg/day), or with control vehicles (1.0 ml/kg/day) for 40 days. Six days after the beginning of the treatments, the animals received identical inoculum concentrations of M. bovis. Hamsters treated with AMPH plus diazepam exhibited: 1) increased weight loss; 2) increased mortality; 3) increased scores of M. bovis colony forming units (CFU) isolated from liver, lung and spleen; 4) increased granuloma areas measured in the liver, lung and spleen. These effects were not induced by AMPH (1.0 or 2.0 mg/kg/day) given alone and were produced by diazepam (2.0 mg/kg/day) treatment per se. Furthermore, AMPH (2.0 mg/kg/day) and diazepam (2.0 mg/kg/day) given alone or in combination for 20 days increased the serum levels of Cortisol in relation to control hamsters, with the effect being higher in the animals treated with both drugs. The present data, which demonstrate an impaired defense against M. bovis in hamsters treated with AMPH plus diazepam or with diazepam alone, were tentatively explained on the basis of a direct and/or indirect action of the drugs on macrophage/lymphocyte activity. In the former case, the effects may be related to stimulation of peripheral benzodiazepine receptor sites (PBR) present on macrophages/lymphocytes and/or to a direct effect of ACTH on immune cells, while in the latter they may be mediated by Cortisol via PBR and ACTH stimulation of the adrenals.     

Effective bleeding control and symptom relief by lower dose regimens of continuous combined hormone replacement therapy: A randomized comparative dose-ranging study

Objectives: We compared two different continuous combined hormone replacement therapy (HRT) regimens of estradiol valerate (E₂V) and medroxyprogesterone acetate (MPA) with a combination of micronized estradiol (E₂) and norethisterone acetate (NETA) to determine bleeding pattern, control of climacteric symptoms, lipid profile, endometrial and general safety in a 1-year multicenter study. Methods: 440 postmenopausal women were randomized to three treatment groups to receive: 1 mg E₂V+2.5 mg MPA; 1 mg E₂V+5 mg MPA; or 2 mg of E₂+1 mg NETA. After the first 6 months, the E₂V dose was increased to 2 mg in both E₂V/MPA groups. Information on bleeding was recorded on diaries by the women and intensity of climacteric symptoms was assessed using VAS scales. Physical and laboratory examinations, endometrial biopsy and vaginal ultrasonography were performed at baseline and follow-up visits. Results: Significantly fewer bleeding days were experienced in the first 3 months by women taking E₂V/MPA compared with women taking E₂/NETA. When the dose of E₂V was increased in the E₂V/MPA groups, an increase in maximum bleeding intensity was observed in the group receiving 2.5 mg of MPA, but not in the group taking 5 mg of MPA. All dose combinations effectively relieved climacteric symptoms and beneficial effects on the lipid profile were seen after 6 months in all groups. Tolerability and endometrial safety were good and no cases of hyperplasia were observed. More women discontinued treatment prematurely in the E₂/NETA group compared with either of the E₂V/MPA groups. The overall continuation rates ranged from 70 to 86%. Conclusions: These results confirm that lower dose combinations of continuous combined HRT are usually sufficient to control symptoms or avoid breakthrough bleeding. However, if higher E₂V dose is needed for symptom control, it should be combined with the higher dose of progestin (5 mg) to avoid bleeding disturbances. Flexible treatment regimens should be available for individualized HRT.     

Pharmacokinetics and biotransformation of orally administered oestrone sulphate and oestradiol valerate in post-menopausal women

The pharmacokinetic properties and biotransformation of two orally active oestrogens, piperazine oestrone sulphate (PE₁S, 2.5 mg/day) and oestradiol valerate (E₂V, 2.0 mg/day), given alone or in combination with levonorgestrel (LNG, 250 μg/day) were compared in 8 post-menopausal women, using a randomized cross-over design.

The end points measured in peripheral plasma included oestrone (E₁), oestradiol (E₂), oestriol (E₃), oestrone sulphate (E₁S), oestradiol sulphate (E₂S) and oestriol sulphate (E₃S). In addition, LNG and sex-hormone-binding globulin SHBG concentrations were also assessed.

The plasma levels of E₃ were invariably below the detection limit (220 pmol/1). The levels of all the other oestrogens analyzed were consistently higher and the area under the curve significantly greater (except in the case of E₃S following PE₁S administration than those recorded after E₂V ingestion.

The terminal half-lives of the circulating oestrogens measured after PE₁S administration did not differ from those found after E₂V administration.

After 21 days of PE₁S administration (in combination with LNG for the the last 10 days), the maximum levels of all the oestrogens (except those of E₂) were significantly higher than those seen after the first dose. No such difference was observed after E₂V administration.

There was no difference between the effects of the two treatment regimens with regard to the E₁/ E₂ ratios, but the E₁/E₁S ratios were significantly lower after PE₁S treatment than after E₂V administration.

It is concluded that, compared with an equivalent dose of PE₁S, daily repeated oral administration of E₂V yields consistently lower peripheral plasma levels of E₂ and its principal metabolites. However, in contrast to PE₁S therapy, prolonged administration of E₂V does not result in an accumulation of the circulating oestrogens measured.     

温针腰神经根受压大鼠前列腺素E2的水平

背景：研究表明温针对降低大鼠腰神经根受压模型中前列腺素E₂表达有重要意义。 目的：探讨温针对大鼠腰神经根受压模型中前列腺素E₂的调节作用,并与针刺和美洛昔康作对比。 方法：60只SD大鼠随机等分为正常组、模型组、美洛昔康组、针刺组和温针组,后4组通过放置硅胶片建立大鼠腰神经根受压模型。美洛昔康组、针刺组、温针组大鼠分别在造模后予以3.75 mg/kg美洛昔康灌胃、针刺和温针腰L₅夹脊穴治疗14 d。 结果与结论：美洛昔康、针刺和温针都可以降低大鼠受压腰神经根组织中前列腺素E₂的水平(P < 0.01),温针较美洛昔康和针刺能更明显地降低前列腺素E₂水平(P < 0.01),提示温针可以有效地降低大鼠腰神经根受压模型中的前列腺素E₂。     

The treatment of postmenopausal vaginal atrophy with Ovestin vaginal cream or suppositories: clinical, endocrinological and safety aspects

Seventy-four postmenopausal women presenting with vaginal atrophy were treated with either Ovestin® vaginal cream (Group A, 23 women: 1 mg/day E₃; Group B, 30 women: 0.5 mg/day E₃) or vaginal suppositories (Group C, 21 women: 0.5 mg/day E₃), applied daily for 3 wk (A and B) or 2 wk (C) before retiring. Ten women from A and 10 from B applied a maintenance dose (1 application twice weekly) during wk 4–16. Effects on vaginal cytology, cervical mucus and clinical and colposcopic findings were studied. Endometrial biopsies were done in 16 patients (A) before and after 3 wk of treatment, and, in 8 of the cases, at 16 wk. A routine laboratory screening program was performed before and after 16 wk of treatment in 10 patients (A). Plasma samples for hormone level determinations were obtained in 32 patients.

Clinical and colposcopic findings showed a beneficial effect of treatments, confirmed by vaginal smears, and persisting during maintenance therapy. Effect on cervical mucus was slight to moderate. No side effects occurred and tolerance was very good. Endometrium remained atrophic under treatment. Screening program revealed no abnormalities. Treatments induced a sharp rise in plasma E₃, followed by a gradual decline. Gonadotropins were slightly suppressed. E₁, E₂, PRL and SHBG capacity remained unchanged.     

Endocrinological and clinical investigations in post-menopausal women following administration of vaginal cream containing oestriol

The maturation value (MV), cervical mucus paråmeters (ferning, Spinnbarkeit), oestrone (E₁), oestradiol (E₂), oestriol (E₃), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), thyrotropin (TSH), growth hormone (GH), sex hormone binding globulin (SHBG), cortico-steroid binding globulin (CBG) and thyroxin-binding globulin (TBG) were determined in 11 post-menopausal women presenting with vaginal atrophy prior to, and following, treatment with Ovestin® vaginal cream containing 0.5 mg/day of E₃ for 8 wk. In 6 of the patients E₃ was measured during frequent plasma sampling on days 1, 21 and 56; in the same patients and on the same days TRH-stimulated PRL, TSH and GH levels were estimated.

While the therapy induced a sharp rise in the MV, there was a moderate effect on ferning/Spinnbarkeit. Baseline E₃ rose from undetectable levels to a mean value of 86.8 pmol/1 at day 21. E₃ levels achieved during frequent plasma sampling were higher on day 1 than on days 21 and 56 - a decline of the areas under the response curves being significant (P₂-sided = 0.03). There was a slight supression of FSH and LH. No changes in the circulating levels of E₁, E₂, SHBG, CBG, TBG, PRL, TSH and GH were seen. TRH-stimulated PRL, TSH and GH levels remained unaffected. Clinical effect was excellent and no untoward effects were reported.     

Comparative metabolic study of percutaneous versus oral micronized 17β-oestradiol in replacement therapy

The aim of this study was to compare the metabolic effects of two presentations of 17β-oestradiol (E₂) which are of recognized effectiveness in the prevention of post-menopausal bone loss, one being administered via the oral and the other via the percutaneous route. During this prospective, randomized study, 32 patients were treated for 2 mth with either 2 mg/day of oral micronized E₂ (n = 16) or 3–5 mg/day of percutaneous E₂ (n = 16). Both regimens proved efficacious, since significant increases in oestrone (E₁) and E₂ concentrations ranging up to mid-follicular values were observed.

In the percutaneous-treatment group we noted a significant decrease in triglycerides (TG), without any significant changes in high-density lipoprotein cholesterol (HDL-C) or low-density lipoprotein cholesterol (LDL-C). In the oral-treatment group, we saw no significant increase in HDL-C, although significant increases were observed in body weight, TG, plasma renin substrate (PRS) and sexhormone-binding globulin (SHBG) as well as significant decreases in antithrombin III (AT III) activity and antigen. All of these metabolic variations led us to the conclusion that oral E₂ at the dose established as effective in preventing post-menopausal osteoporosis may, even when micronized, alter certain metabolic and haemostatic parameters in a population characterized by increases in cardiovascular risk factors and morbidity. Oral oestrogen replacement therapy should therefore continue to be used only in carefully selected patients and be strictly followed up by systematic checks on a series of metabolic criteria.     

Long-term effects of percutaneous estradiol on bone loss and bone metabolism in postmenopausal hysterectomized women

Objective: To determine whether percutaneous estradiol (pE₂) (1.5 mg/day) is able to counteract the postmenopausal bone loss in postmenopausal hysterectomized women, in a double-blind study versus oral estriol (E₃) (2 mg/day). Methods: The bone mineral density of the lumbar spine (LS) and of the proximal femur (PF) was measured every 3 months by dual energy X-ray absorptiometry for 2 years in 43 hysterectomized postmenopausal women (21 in the E₂ group and 22 in the E₃ control group), and in a subset of patients for a 3rd year. The statistical analyses were performed on Macintosh using StatView II^TM. Results: A significant bone loss of 1.2 (0.4)% and of 1.3 (0.3)% per year was observed in the control group, respectively at LS and at PF, versus a significant gain of 1.2 (0.5)% per year in the treated group at the LS. No significant change at PF occurred in the treated group. In the 20 patients followed up for a 3rd year on pE₂, an increase of 1.2 (0.9) and 2.5 (1.4)% at LS in the 12 former active group patients and the eight formerly control patients, respectively was seen. The same trend was observed at the proximal femur. Conclusion: pE₂ (1.5 mg E₂) is able to counteract the postmenopausal bone loss in hysterectomized women, whereas E₃ (2 mg/day administered orally) is unable to maintain bone mass.     

Serum levels of oestrogens, progesterone, follicle-stimulating hormone and sex-hormone-binding globulin during simultaneous vaginal administration of 17β-oestradiol and progesterone in the pre- and post-menopause

Serum concentrations of 17β-oestradiol (E₂), unconjugated oestrone (E₁), total oestrone (tE₁), progesterone (P), follicle-stimulating hormone (FSH) and sex-hormone-binding globulin (SHBG) were measured before and after daily intravaginal administration of 250 μg micronized E₂ and 10 mg micronized P for 14 days to 12 post-menopausal and for 1 day only (during cycle days 5–8) to 11 pre-menopausal women. In the post-menopausal women the levels of all steroids increased to maximum values on day 1, 8–10 h after administration and fell thereafter. In the pre-menopausal women the steroid concentrations rose slowly to a plateau level 10–15 h after administration. Significantly higher absorption of E₂ and E₁ (area under the curve increments) was noted in the post-menopausal than in the pre-menopausal women.

In the post-menopausal women the steroid levels measured on days 7 and 14 corresponded to those observed in the very early or late luteal phase. Area under the curve increments were usually smaller on days 7 and 14 than on day 1 and the absorption kinetics altered to a ‘pre-menopausal’ pattern. FSH levels were significantly reduced as from 12 h after administration on day 1 and onwards. A slight (10%) but significant increase in SHBG levels was noted on day 14. It was concluded that the combined E₂ and P treatment used in this investigation brings about a physiological response with only minimal side effects on the liver as judged from changes in SHBG concentrations.     

雌激素对大鼠红核神经元保护作用的体视学定量

目的 观察雌激素（E₂）替代治疗对去卵巢SD大鼠脊髓损伤后红核神经元逆行性损伤的影响。方法 成年雌性SD大鼠80只, 随机分为正常组、红核脊髓束(RST)损伤组、E2替代治疗组、雌激素受体拮抗剂（ICI）治疗组和E₂+ICI联合治疗组。SD大鼠去势后1周采用选择性切断脊髓C3～C4左侧背外侧索制作单侧红核脊髓束（RST）横断损伤模型,给予不同条件治疗后1周、2周和4周对各组大鼠采用前肢支撑探测实验进行行为学评价,用红色荧光金（FR）逆行荧光示踪及体视学定量分析法,观察红核神经元的形态及数目变化。结果 前肢支撑探测实验结果显示,各时间点E2替代治疗组的左前肢使用率均高于除正常组外其他各组,但无统计学意义（P >0.05）;形态学检测结果可见各组大鼠中脑右侧FR阳性红核神经元数目除正常组外均有不同程度减少,尤以4周时最为明显。E2替代治疗组右侧中脑FR阳性红核神经元与RST损伤组、ICI治疗组和E₂+ICI 联合治疗组相比胞体饱满、轮廓清晰、突起长,体视框计数结果显示,E₂替代治疗组红核FR阳性神经元数目明显多于其余各组（P<0.05）,但RST损伤组、ICI治疗组和E₂+ICI联合治疗组之间右侧中脑FR阳性红核神经元数目未见明显差异（P>0.05）。结论 大鼠脊髓横断损伤后中脑红核神经元发生逆行性损伤,E₂替代治疗可减轻脊髓损伤引发的继发性红核神经元损伤。     

颈椎后纵韧带骨化累及C2椎体对颈椎矢状面参数影响的影像学研究

目的 探讨累及C₂椎体的颈椎后纵韧带骨化症（OPLL）对颈椎矢状面形态及其参数的影响。方法 回顾性研究。纳入2016年1月—2020年12月徐州医科大学附属医院脊柱外科颈椎OPLL患者97例,其中男68例、女29例,年龄37~80（59.0±9.6）岁。根据骨化物是否累及C₂椎体将患者分为2组,OPLL累及C₂椎体36例为C₂阳性组,未累及C₂椎体 61例为C₂阴性组。在立位颈椎侧位X线片上测量C_0~2及C_2~7颈椎前凸角（CL）、C₂倾斜角（C₂S）、胸廓入口角（TIA）、T₁倾斜角（T₁S）、颈倾角（NT）、枕颈倾斜角（OCI）、C_2~7矢状轴距离（SVA）等矢状面参数。观察项目：（1）对比2组患者性别、年龄、日本骨科协会（JOA）评分、颈椎功能障碍指数（NDI）评分等临床一般资料;（2）比较2组患者骨化物累及的颈椎节段、椎管侵占率、OPLL分型以及影像学上有无脊髓高信号、骨化物是否触及K线的情况;（3）比较2组间颈椎矢状面各项影像学参数的差异,分别对2组内矢状面各影像学参数进行相关性分析;（4）对OPLL累及C₂的危险因素进行多因素logistic回归分析。结果 2组患者性别、年龄、JOA评分差异均无统计学意义（P值均>0.05）。C₂阳性组骨化物累及颈椎节段数（4.6±1.2）个、椎管侵占率52.42%±9.96%、NDI评分（21.08±7.65）分,均高于C₂阴性组的（3.1±0.9）个、45.87%±13.08%、（17.70±8.49）分,差异均有统计学意义（P值均<0.05）。在OPLL分型上,C₂阳性组和C₂阴性组分型构成比差异有统计学意义（P<0.001）。2组间骨化物触及K线率、脊髓高信号率差异均无统计学意义（P值均>0.05）。颈椎矢状面各项影像学参数中,仅C₂阳性组C₂S（11.25°±5.84°）高于C₂阴性组（7.66°±5.65°）,差异有统计学意义（t=2.99, P=0.004）。2组内颈椎矢状面影像参数相关性分析显示：C₂阳性组中,C₂S与C_0~2CL、C_2~7SVA呈正相关（r=0.52、0.80,P值均<0.05）;C₂阴性组中,C₂S与C_0~2 CL、C_2~7SVA呈正相关,与C_2~7CL呈负相关（r=0.43、0.71、-0.39,P值均<0.05）。多因素logistic回归显示,C₂S增大[比值比（OR）=1.208,95%可信区间（CI）1.032~2.210,P=0.014]和骨化物累及颈椎节段数（OR=3.026,95% CI 2.136~5.076,P=0.001）为OPLL累及C₂的独立性危险因素。结论 颈椎OPLL累及C₂者以累及节段更多和椎管侵占率更高为特点,在颈椎矢状面影像学参数上表现为更高的C₂S,且C₂S和骨化物累及颈椎节段数为OPLL累及C₂的独立危险因素。     

The effect of oral hormone replacement therapy on lipoprotein profile, resistance of LDL to oxidation and LDL particle size

Objectives: To disclose if oral estradiol (E₂), alone or in combination with natural progesterone (P) or medroxyprogesterone acetate (MPA), may modify the oxidizability of low density lipoprotein (LDL), and if the effect is achieved at physiological dosages. LDL oxidizability was assessed by the resistance to oxidation by copper and by the particle size profile, since small particles have increased oxidation susceptibility. Methods: Thirty-three women received two consecutive, two-month length doses of 1 and 2 mg/day of oral E₂. They were then randomly assigned to a fourteen-day treatment of 2 mg/day E₂ plus either 300 mg/day P or 5 mg/day MPA. A parallel group of experiments was performed on a pool of baseline plasma, where hormones were added at the desired concentration. Lipoprotein levels, resistance of LDL to oxidation, and LDL particle diameter, were measured at baseline and after each treatment. Results: Estradiol reduced LDL levels and increased high density lipoprotein (HDL) and triglycerides. P abolished these changes, whereas MPA only reversed the increase of HDL. Estradiol protected LDL from oxidation in a dose-dependent manner, although only at pharmacological concentrations (1 μM or higher). Both P and MPA were inert at either physiological or pharmacological concentrations. The size of the LDL particles remained unaffected except under MPA, in which it was reduced. Conclusions: Estradiol has a protective effect against LDL oxidation, although only at pharmacological dosages. P and MPA did not limit the E₂ action. The size of the LDL particles remained unaltered after each E₂ dose, but MPA, and not P, was associated with a diminution.     

Hormone levels in healthy post-menopausal women and in women with post-menopausal bleeding with or without endometrial carcinoma

FSH, oestrone (E₁), 17β-oestradiol (E₂) and androstenedione (A) were determined in 250 healthy pre- and post-menopausal women, with ages ranging from 40 to 78 yr. These hormone levels were not found to have changed significantly in women of this stable, post-menopausal phase after the age of 54. The results found in this group of women (n = 107), who now range between the ages of 55 and 78, were compared with results from two groups of women who were found to have gynaecological disorders. The first group consisted of 45 women with post-menopausal bleeding without endometrial carcinoma. The second group consisted of 38 women with post-menopausal bleeding and endometrial carcinoma.

FSH was determined by double-antibody radioimmunoassay. E_l, E₂ and A were fractionated chromatographically after extraction with ether and determined radioimmunologically. The data were analysed using the Kruskal—Wallis test and the Wilcoxon test.

When comparing the measurement of hormone levels in the healthy group of women with that of women with post-menopausal bleeding without endometrial carcinoma, no differences were found. However, in the group of women with post-menopausal bleeding and endometrial carcinoma, lower levels of FSH and E₂ and increases in the E₁/E₂ ratio were found; both changes were statistically significant. The slight increase in E₁ and A found in these women was not significant. Any changes which occur in the hormone levels of women with endometrial carcinoma may indicate a correlation between hormones and the onset of endometrial carcinoma.     

涉及C2水平的长节段颈椎后纵韧带骨化症的手术疗效观察

目的 探讨涉及C₂水平的长节段颈椎后纵韧带骨化(OPLL)症的手术方式及疗效。方法 对2011年5月—2014年11月第二军医大学附属长征医院脊柱外科手术治疗的42例涉及C₂水平长节段OPLL症患者的临床资料进行回顾性研究。其中男22例、女20例,平均年龄56.2岁。依术式不同将其分为A、B两组,A组21例行单纯C_3～7后路椎管扩大成形术,B组21例行C_3～7后路椎管扩大成形加C₂椎板下缘减压术,比较两组患者术后JOA评分及评分改善率、颈椎曲度及C_2～3椎体间活动度。结果 42例患者均顺利完成手术。A组中1例术后发生C₅神经根麻痹,A组中1例、B组中2例术后出现轴性疼痛,予相应处理后痊愈。术后随访6个月～4年,平均随访2.1年。术后3个月及末次随访时B组JOA评分及评分改善率均高于A组,差异均有统计学意义(t值分别为7.203、6.644,P值均＜0.01)。术后3个月及末次随访时两组患者颈椎曲度及C_2~3椎体间活动度差异均无统计学意义(P值均＞0.05)。结论 对于涉及C₂水平长节段颈椎OPLL症患者,若K线阳性,行C_3~7后路椎管扩大成形加C₂椎板下缘减压术,可以取得满意疗效。     

Metabolic clearance rate of oestrone sulphate in post-menopausal women

The feasibility of using constant infusions of unlabelled oestrone sulphate (E₁S) for the purposes of calculating its metabolic clearance rate (MCR_E1S) and its conversion ratios to oestrone (E₁) and oestradiol (E₂) in post-menopausal women was exploited in this study.

The results obtained by the infusion of unlabelled E₁S were similar to those obtained by the infusion of labelled steroid.

The MCR_E1S values seen in our group of post-menopausal women fell within the range previously reported for fertile women.

The contribution of E₁S to circulating E₁ averaged 18% (range 14–24%), indicating that the E₁S-E₁ equilibrium should be taken into account during studies on oestrogen balance in post-menopausal women.     

Benefits and risks of different hormonal replacement therapies in post-menopausal women

A total of 113 women who presented with climacteric symptoms participated in the study. They were randomly allocated to seven groups of 10–27 subjects, who received for 6 mth the following therapies, respectively: (1) conjugated oestrogens (CE) 0.625 mg/day for 21 days + norethisterone (NET) 5 mg/day from day 12 to day 21; (2) CE + cyproterone acetate (CPA) 12.5 mg/day from day 1 to day 10; (3) oestradiol valerate (EV) 2 mg/day for 21 days + NET; (4) EV + CPA; (5) oestriol (E₃) 2–4 mg/day; (6) tibolone (ORG OD14) 2.5 mg/day; and (7) placebo, one tablet/day.

Hot flushes decreased significantly over the treatment period in all seven groups. However, E₃ was less effective at the dose used than CE, EV or ORG OD 14. At the end of the 6 month treatment period histological examination revealed no changes in endometrial morphology in any of the patients treated. Indeed, the addition of a progestogen even induced regression of endometrial hyperplasia in 8 cases.

No significant variation in the plasma levels of tryglycerides, total cholesterol, high-density lipoprotein (HDL) or low-density lipoprotein (LDL) was observed after the second and sixth months of treatment with E₃ or ORG OD 14. After 6 months, treatment with CE/EV + CPA produced a significant increase in HDL, while treatment with CE/EV + NET brought about a reduction in total cholesterol and HDL and an increase in LDL.     

Metabolic clearance rates of androgens and oestrogens in ageing women

Using the constant infusion technique we have measured the metabolic clearance rates (MCR) for Δ⁴-androstenedione (A), testosterone (T), oestrone (E₁) and oestradiol (E₂) in a large group of postmenopausal women. Their mean ± SE age was 64.5 ± 1.6 yr, their ages ranged from 46–90 yr. When the MCRs for each steroid were related to age by linear regression analysis no significant correlation was found for any of the steroids. Similarly, when the women were grouped according to their age by decade, the mean MCR for each steroid showed no trend with increasing age.

There was no difference in the MCRs for A, T and E₁ of the post-menopausal women and a large group of pre-menopausal women. However, there was a significant decrease in the mean MCR for E₂ between the two groups which is probably related to the marked decrease in circulating E₂ in postmenopausal women. We conclude that for these steroids age, per se, does not appear to be a major determinant of the MCR.     

Effects of intravaginal oestrogen treatment upon the vaginal absorption of conjugated equine oestrogens

Conjugated equine oestrogens (0.625 mg) were administered daily and intravaginally to 7 post-menopausal women (aged 70–93 yr) for 14 days. Blood samples were taken at days 1 and 14 immediately before and 2, 4 and 6 h after oestrogen application and at days 4, 6, 8, 11 and 13, 4 h after application. Serum samples were analyzed with respect to total oestrone (E₁), unconjugated 17β-oestradiol (E₂), FSH and LH. Serum total E₁ and E₂ increased rapidly at day 1 to luteal and follicular phase levels respectively. After that total E₁ levels decreased to a plateau corresponding to follicular phase values and remained at that level throughout the treatment period. Serum E₂ remained at the follicular phase level during the entire period of treatment. No increase in serum oestrogens could be detected after oestrogen application at day 14. Serum gonadotrophins were already suppressed at day 4 and further decreased to premenopausal values during the latter half of the treatment period. It is speculated that the effects of oestrogens upon a post-menopausal vaginal mucosa involves a diminished resorption of conjugated oestrogens. This effect is, however, not sufficient to avoid systemic effects at the dosage used.