雌激素对幼年大鼠子宫肌层影响的光镜、组织化学和电镜观察

本文使用常规H—E染色和组织化学方法(PAS反应和甲绿-哌洛宁法)初步观察了雌激素对幼年大鼠子宫壁肌层的细胞形态变化。最显著的变化是:平滑肌细胞体积增大;不仅在子宫壁平滑肌纤维中并且在血管平滑肌细胞中,有大量的PAS阳性颗粒;平滑肌细胞中RNA中度增多。我们也在电镜下观察了它们的超微结构改变。结果表明,实验组的平滑肌细胞和成纤维细胞与对照组相比粗面内质网增多并有池扩张。     

雌激素对大鼠肝再生过程中肝细胞超微结构的影响

本文采用形态测量技术,分析了雌激素对大鼠肝再生过程中肝细胞超微结构的影响。结果显示,使用雌激素的大鼠肝细胞核及核仁体积明显高于对照组,以术后1～3d最明显(P<0.001);同时,线粒体数密度也明显增加,术后1、3、7d与对照组比较差异有极显著性意义(P<0.01),表明雌激素具有促进肝再生过程中肝细胞线粒体增生的作用。作者认为,雌激素的上述作用是雌激索促进肝细胞再生的形态学表现。     

Effects of antiandrogen-estrogen treatment on sexual and endocrine parameters in hirsute women

Sexual activity was evaluated in 51 women with hirsutism associated with increased levels of circulating androgens before and while on combined treatment with the antiandrogen cyproterone acetate (CA) and ethinyl estradiol (EE₂) and compared to a reference group of 52 subjects. The percentage of unbound testosterone (T) was higher (p < 0.001), the coital frequency lower (p < 0.05), and the masturbation frequency higher (p< 0.04) in hirsute women. Mean frequency of total activity (coitus plus masturbation) was similar in the two groups. Treatment with combination of CA and EE₂ resulted in a decline of unbound T (p< 0.001). There was no change of total sexual activity, but coital frequency increased (p < 0.05) and masturbation frequency declined (p < 0.04). It is concluded that raised levels of circulating androgens, as judged by free T concentration, are not of crucial importance in the expression of sexual behavior in hirsute women.     

Bleeding patterns in recent postmenopausal outpatients with uterine myomas: comparison between two regimens of HRT

Objectives: To evaluate and to compare the bleeding patterns obtained with two regimens of hormone replacement therapy given to early postmenopausal women with asymptomatic uterine leiomyomas. Methods: In this randomised prospective 1-year study 50 early postmenopausal women with one to four asymptomatic uterine leiomyomas were enrolled into two study-groups to take two regimens of hormone replacement therapy for 12 28-day cycles: (A) Tibolone, 2.5 mg/day; (B) conjugated equine estrogens (CEE), 0.625 mg/day plus medroxyprogesterone acetate (MPA), 5 mg/day. The bleeding patterns and the changes in uterine volume of the 47 outpatients who completed the study were evaluated and compared. Results: Amenorrhea incidence was higher in group A (75.0% of the cycles) than in group B (65.6% of the cycles), while irregular bleeding and irregular spotting incidences were higher in group B (29.7 and 4.7% of the cycles, respectively) compared to group A (22.6 and 2.4% of the cycles, respectively). The mean bleeding and spotting lengths were not statistically different between patients in group A and those in group B. Finally, at the end of the study period transvaginal ultrasonography showed no significant change in leiomyoma size. Conclusions: The results demonstrate that, in early postmenopausal patients with asymptomatic uterine leiomyomas, Tibolone treatment seems to be preferable compared to CEE–MPA continuous combined treatment in relation to the lesser occurrence of irregular bleeding. Furthermore, neither Tibolone nor CEE–MPA therapy, at the doses used here, promote fibroid growth.     

Use of serum-free hormonally defined media to evaluate the effects of growth factors and inhibitors on proliferation of estrogen-responsive mammary and pituitary tumor cells in culture

Summary Serum-free defined media have been developed for assay of the mitogenic effects of growth factors on human MCF-7, human T-47D, and mouse COMMA-D mammary cells as well as for identification of mitogens and inhibitors of GH₄C₁ rat pituitary tumor cell growth. These lines were shown to grow in vivo in response to a variety of hormones including estrogens and thyroid hormones. With mammary cells, complete hormonally and nutritionally defined media were established that supported continuous passage at 50 to 90% of the serum stimulated rate. The strategy used to measure mitogens for mammary cells was to identify nutritional conditions where the growth rate was reduced greatly without impairing the response to picomolar to nanomolar concentration of growth factors. The effects of polypeptide growth factors and tissue extracts were estimated by their addition to basal medium and measuring cell number increases or labeled thymidine incorporation into DNA. In a variation of this methodology, the MTW9/PL2 rat mammary cells were used to identify secreted autocrine growth factors; nutritionally defined conditions were sought for growth of these rat cells in the complete absence of exogenous growth factors. The factors secreted into the medium were detected by bioassays with COMMA-D or MCF-7 mammary cell lines. The effects of growth factors-inhibitors on pituitary cells were measured by a related method; the GH₄C₁ cells were grown at less than optimal rates in a defined medium designated TRM-1. Addition of mitogens to TRM-1 stimulated pituitary cell growth whereas addition of inhibitors caused reduced levels of growth. The methods described in this report offer new means of assaying growth factors-inhibitors for a range of mammary and pituitary tumor cells.     

Hormonal contraception without estrogens

The long-term clinical effects of ethinyl estradiol and the impact on environmental safety of the alkylated estrogen components used in combined contraceptive pills remain the subject of debate. The development of improved methods for the use of progestogen-only contraception would represent a viable and desirable option. Several progestogen compounds are not alkylated, and these can be delivered through a variety of routes. Some of the progestogen-only methods are well established in clinical use. Estimates for both perfect and typical effectiveness are less than one pregnancy per 100 woman-years with oral, injectable, implantable and intrauterine methods. In practice, with the oral progestogen-only method, perfect and typical effectiveness range from three to five pregnancies per 100 woman-years. The main side effect with all progestogen-only methods is unpredictable vaginal bleeding during the first months of use, and this may lead to discontinuation. Nevertheless, continuation of use is more frequent if patients are well informed of this side effect before treatment begins. No cardiovascular- and cancer-related side effects have been proven.     

Effect of megestrol caproate on the reproductive function of laboratory animals

In vivo experiments on rats and rabbits showed that megestrol caproate, a 17-alpha-hydroxyprogesterone derivative exhibits 10-fold higher gestagenic activity compared to progesterone and possesses no androgenic, anabolic, and estrogenic activities.     

Endogenous sex hormone levels and breast cancer risk

Sex-steroid hormones are a major determinant of the risk of breast cancer. We evaluated the relationship between obesity and endogenous estrogen levels in 79 healthy, postmenopausal women. Thirty-nine of the women were siblings of patients with postmenopausal-onset breast cancer; the remaining women were age-matched (+/- 10 yr) controls. Our hypothesis was that the siblings of the breast cancer patients would weigh more and that this excess weight would lead to higher serum estrone levels. The choice of unaffected family members of breast cancer patients reduces the concern that results may have been influenced by the cancer rather than antecedent to its development. Our findings demonstrated a statistically significant excess estrone level in the siblings compared to the controls (58.9 vs 47.8 pg/ml, P = 0.005). The siblings weighed 4.3 kg more than the controls. Matched pairs analysis (sibling-control), adjusting for weight, also showed significant differences in serum estrone levels. These differences were observed despite comparability in dietary intake, medication use, and personal medical history. These findings represent the first time that higher estrogen levels have been measured in siblings of postmenopausal breast cancer patients. This observation may represent an important link in our understanding of the relationship between genetic and environmental risk factors of breast cancer. One approach to subsequent genetic studies of breast cancer may be to focus on the possible biological determinants such as sex-steroid hormone level receptors, oncogenes, and gene products and not on the "familial aggregation" of breast cancer.     

Effect of Chronic Aromatase Inhibition by Δ1 -Testolactone on Pituitary-Gonadal Function in Oligozoospermic Men

Aromatase inhibition by delta 1-testolactone (Teslac, 500 mg twice daily) for 6 months in 9 patients with idiopathic oligozoospermia lowered the levels of serum estradiol (E2) and thereby sex hormone binding globulin (SHBG) (rS = +0.40, p less than 0.025) to values -35 and -25%, respectively, below the pretreatment values (P less than 0.001 and less than 0.005). The E2 decrease was accompanied by a temporary increase (+50%) in the levels of follicle stimulating hormone (FSH), not of luteinizing hormone (LH), and of 17 alpha-hydroxyprogesterone (17 alpha-OHP), but less of testosterone (T) (+30%), which led to a transient rise in the 17 alpha-OHP/T ratio. The T/E2 ratio and "free T" index (T/SHBG) almost doubled until the end of the treatment period. During delta 1-testolactone treatment the mean sperm density gradually rose from 8.1 +/- 1.3 (SEM) before to 21.3 +/- 6.7 X 10(6)/ml after 6 months (P less than 0.01), whereas the total sperm count almost threefold increased (P less than 0.05). Sperm concentrations exceeding 20 X 10(6)/ml were achieved in 4 of the 9 patients. Two of these patients' wives became pregnant. Although the data point to a pivotal role of estrogens in the pathogenesis of the spermatogenic lesion in some patients with idiopathic oligozoospermia, the lack of a beneficial effect of estrogen lowering in others points to a multicausal nature of the disease entity.