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PubMed1985

Primary hormonal therapy of advanced breast cancer with megestrol acetate: predictive value of estrogen receptor and progesterone receptor levels.

Estrogen (ER) and progesterone receptor (PR) levels in human breast cancer have been shown to have value in predicting response to a variety of hormonal therapies. However, the relationships between steroid receptor levels and tumor response and survival in patients treated with progestational agents for primary hormonal therapy have not been clearly defined. Forty-three advanced breast cancer patients, whose tumors had been assayed for ER and PR were treated with megestrol acetate as initial hormonal therapy. Twenty-five patients had ER and PR levels greater than 10 femtomole/mg cytosol protein, and the median ER and PR levels for the entire group were 114 fmol/mg and 100 fmol/mg, respectively. The overall response rate (complete and partial) was 46%, with a median duration of response of 66 weeks. Seventy percent of patients whose ER and PR were greater than 10 fmol/mg responded: Step-wise discriminant analysis showed that ER and PR were significantly related to response and that PR was the best predictor of response (P = .0034). Similarly, both ER and PR were significantly related to survival (P = .0001 for PR and P = .021 for ER). These data indicate that megestrol acetate is effective primary hormonal therapy in advanced breast cancer patients, and that ER and PR levels were significantly related to response and to survival duration. PR proved to be the best predictor of response in this group of patients.

Aged↗
PubMed1994

Arias-Stella reaction in nonpregnant women: a clinicopathologic study of nine cases.

The Arias-Stella reaction (ASR) is a common and universally recognized feature of gestational endometrium. That identical cytologic changes may, on occasion, occur outside the endometrium or in nonpregnant women is not as well documented. This report describes the clinical and pathologic findings in nine nonpregnant women whose endometria demonstrated ASR. The defining characteristics of ASR, associated pathologic changes, and differential diagnosis are discussed. All of these women were peri- or postmenopausal, and eight of nine had received exogenous hormones, most (n = 7), progestational agents. ASR did not persist in the four patients who underwent subsequent endometrial examination. None of these patients developed adenocarcinoma, although follow-up was short. ASR is an unusual response to hormonal therapy in nonpregnant patients. It is important to recognize the phenomenon in this setting and not overinterpret the characteristic cytologic atypia as adenocarcinoma.

Adult↗
PubMed1985

Characterization of hematogenous cellular constituents of the murine decidua: a surface marker study.

Decidual tissue, which includes typical (stromal type) decidual cells as well as infiltrating leukocytes, appears to play a local immunoregulatory role in the maintenance of pregnancy in nature. The present study evaluated the contribution of numerous leukocyte subsets characterized on the basis of morphology combined with cell surface markers to the development of murine decidua during syngeneic (CBA female X CBA male) and allogeneic (CBA female X C57BL/6 male) pregnancy. Collagenase dispersed decidua were subjected to total and differential counts and cell surface labeling for a radioautographic identification of various markers: S-IgM on B cells, Thy-1 on T cells, neither marker on null lymphocytes, Lyt- (1 or 2 or 1,2) antigens on T cell subsets, Mac-1 and I-A on macrophages, using 125I-labeled monoclonal antibodies or a sandwich labeling with 125I-protein A. The total cellularity of decidua basalis showed a biphasic rise in both pregnancies, with peaks on day 11 and days 15 and 16, but the allopregnant decidua showed a higher accumulation of all cell types indicating that an allogeneic conceptus causes an augmented deciduogenesis. The number of decidual cells, the most frequent cell class, rose to a peak on day 11 followed by a decline possibly due to cell death. The number of lymphocytes, the next frequent cell class, showed a parallel pattern initially, followed by a sharp secondary rise on day 16. This rise may be due to a withdrawal of progesterone, an antiinflammatory hormone. Null cells predominated amongst decidual lymphocytes (45-80%), as well as in the progestational endometrium (53%), indicating a hormonal control of their accumulation. The frequency of B cells was low (10-13%) and T cells (25-45%) comparable to that in the blood, with Lyt-1 only class being the most common T cell subset. Allopregnant decidua also showed a late rise in the total number of Lyt-2 only cells which may have a suppressor function. Macrophages, the next common leukocyte class, all expressed Mac-1. Their number rose to a plateau by day 12, but at a higher level in allopregnancy. I-A (needed for antigen presentation) was expressed by an increasing proportion (5-60%) of macrophages with advancing gestation. These findings provide a basis for further functional studies.

Animals↗
PubMed1985

[Which endocrine treatment is preferred today for prostatic carcinoma?].

There is so far no evidence that the newest hormone compounds, such as progestational agents, antiandrogens or estramustine phosphate, yield better results than low dose estrogens or orchidectomy in previously untreated patients. Castration and the other modalities of androgen deprivation, although they can cause a measurable objective regression in less than half of cases, do often induce a marked, sometimes long-lasting subjective improvement and can delay progression. It has not yet been clearly established whether or not hormone therapy can bring about a prolongation in survival. The critical point still remains our poor understanding of the causes of acquired hormone resistance and our inability to prevent it. Further studies on hormone receptors and steroid metabolism in normal and neoplastic cells might lead to progress in this field. The unsolved problem, whether resistance is due to a selection of clones resistant to hormones ab initio or to acquired biochemical characteristics in cells that were initially responsive, might be of great practical significance. A reliable test, able to detect sensitivity or resistance towards hormone therapy before any treatment is given, would be extremely helpful. Unfortunately, neither the most sophisticated hormone balance studies nor receptor determinations have led to clinically useful implications.

Androgen Antagonists↗
PubMed2007

Arias-Stella reaction in upper genital tract in pregnant and non-pregnant women: a study of 120 randomly selected cases.

AIMS: 1. To study the diagnostic importance of the Arias-Stella reaction. 2. To study tubal epithelial changes in ectopic pregnancy. 3. To study the occurrence of Arias-Stella reaction in non-pregnant women receiving hormonal treatment. METHODS: A prospective study was conducted on 120 patients who underwent endometrial curettage and/or salpingectomy. The patients were divided into four groups, each comprising of 30 patients. Groups 1 and 4 included non-pregnant patients who were being evaluated for infertility and dysfunctional uterine bleeding respectively, while pregnant patients were included in Group 2 (intra-uterine abortions) and Group 3 (ectopic tubal gestation). The endometrial curettings and fallopian tube lining epithelial cells were examined for the changes described by Arias-Stella. Cases which showed the presence of the Arias-Stella reaction were further classified. RESULTS: The changes of the Arias-Stella reaction in endometrial glands were observed in 80% cases of intra-uterine abortions. Secretory/hypersecretory pattern was the most commonly observed type (36.67%). The reaction was seen in 3.33% each of patients evaluated for infertility and patients on hormonal therapy with oral progestational agents for the management of dysfunctional uterine bleeding. Although uncommon, the Arias-Stella reaction was noted in the epithelium of fallopian tubes (16.67%) from patients with ectopic tubal gestation. CONCLUSION: The findings of the present study emphasize the diagnostic importance of the Arias-Stella reaction. The changes of the reaction are a histological clue to the presumptive diagnosis of the presence of chorial tissue in cases in which the chorionic material is not found in the endometrial biopsy. The morphological features can be mistaken for malignancy if the pathologist is not aware of the patient's pregnancy or history of hormonal intake.

Abortion, Induced↗
PubMed1981

[Hormonal dependency of experimental mammary tumors induced by an estro-progestational combination].

Mammary tumours were induced in rats by administration of an estradiol-progesterone association. These tumours offered close analogies with human mammary tumours. The estradiol-receptor was found both in cytosol and nuclei and was more abundant in nuclei than in cytosol. The major part of its binding sites was occupied by endogenous hormone. On the other hand, a high level of progesterone receptor was present in tumoral cytosol. This fact gave evidence of the complete activity of the estradiol receptor. The presence of estradiol and progesterone receptors in mammary tumors induced by these hormones substantiate their hormone-dependence.

Animals↗
PubMed1986

Steroids and related products. LIII. The synthesis of 11-oxa steroids. V. The synthesis of 17-ethynyl-11-oxatestosterone.

The synthesis of 17-ethynyl-11-oxatestosterone, both from 11-oxa-5 alpha-pregnane-3,20-dione and, via a 3,17-dioxygenated 9-oxo 9,12-seco 11-nor 5 alpha-androstane-12-oic ester, from 3 beta-acetoxy-17-hydroxy-5 alpha-pregnan-12-one--two products available from hecogenin--is reported. The new hormone analogue shows significant progestational activity in the Clauberg test and relatively weak activity in a post-coital antifertility assay.

Progesterone Congeners↗
PubMed1980

Effects of progestin-estrogen combination and progestational contraceptives on pituitary gonadotropins, gonadal steroids and sex hormone-binding globulin.

The effects of three kinds of hormonal contraceptives on the levels of follicle-stimulating (FSH), luteinizing hormone (LH), estradiol, progesterone, testosterone, and sex hormone-binding globulins (SHBG) in three groups of normally menstruating women were analyzed. During the administration of a very low-dose combination of 150 micrograms of D-norgestrel and 30 micrograms of ethinylestradiol, a progressive suppression of LH, FSH, estradiol, and (to a lesser extent) testosterone levels was observed while progesterone stayed at levels found during the early follicular phase. SHBG levels in these subjects were within the normal range for women. Oral treatment with 0.5 mg of lynestrenol and the intramuscular administration of 200 mg of norethindrone enanthate produced a suppression of LH but not FSH in all cases. Estradiol levels showed peaks in the three women treated with lynestrenol and in half of those treated with norethindrone enanthate, suggesting follicular activity caused by the unsuppressed FSH stimulus; the subsequent elevation of progesterone in two subjects suggested some luteinization, although there was no evidence of an ovulatory surge of gonadotropins. The SHBG in four subjects treated with norethindrone enanthate fell within our normal range for men, and the mean serum testosterone levels fell 40% below the normal basal levels in these cases.

Adult↗
PubMed2004

Re-evaluation of secondary amenorrheic patients one year after initial diagnosis: a prospective study.

OBJECTIVES: The aim of the study was to re-evaluate women with secondary amenorrhea one year after the first visit evaluation. STUDY METHODS: One hundred and seventy-five women with secondary amenorrhea were evaluated on the first visit. Their ages ranged from 18 to 29. Secondary amenorrhea was defined by the absence of menses for more than 3 months after excluding pregnancy. Women who were attempting to conceive were excluded from the study. 1) One hundred and two women were anovulatory (2) 36 had hypogonadotropic hypogonadism, 3) 11 had hypergonadotropic hypogonadism, and 4) 21 had hyperprolactinemia, 5) and five fell into other categories. The one hundred and forty-nine women in categories 1) to 3) were followed up for one year after the first diagnosis was made. A monthly progestational agent or HRT (hormone replacement therapy) was given to women with anovulation or hypogonadism, respectively. RESULTS: Of the 149 women in categories 1) to 3), 100 could be evaluated one year after the first diagnosis. There were 31 women whose diagnosis was changed. Anovulation changed to hypogonadotropic hypogonadism in 11 women, oligomenorrhea in four, and normal ovulatory cycle in two. Hypogonadotropic hypogonadism changed to anovulation in nine women, and to normal ovulatory cycle in one. Hypergonadotropic hypogonadism changed to normal ovulatory cycle in two women. CONCLUSIONS: A significant finding is that approximately one third of the women initially diagnosed with secondary amenorrhea, upon re-evaluation within one year had their diagnosis changed. Therefore evaluation of amenorrhea at an appropriate time is critical for proper management.

Adolescent↗
PubMed1990

Progesterone regulation of prolactin release from human endometrial stromal cells in culture: potential bioassay for progestational activity.

Prolactin was produced by endometrial stromal cells, but not by epithelial cells, in primary culture. Production was stimulated by progesterone in a time and dose (1-1000 nmol/l) dependent way. Stimulation was started one day after plating. The release of prolactin started one day earlier in cultures from luteal phase than proliferative phase endometria. The responsiveness to progesterone declined with time in culture, sooner in luteal than in proliferative phase cultures, but could, at least partly, be maintained by including estradiol (10 nmol/l) in the medium. Lost response to progesterone could be restored by stimulation with estradiol for two days. The results indicate that prolactin synthesis in the endometrium is regulated directly by progesterone, and indirectly by estradiol. We suggest that prolactin production in primary stromal cell cultures could serve as a bioassay for progestational activity of steroid hormones in the human endometrium.

Adult↗
PubMed1975

Estriol prevention of mammary carcinoma induced by 7,12-dimethylbenzanthracene and procarbazine.

The concentration of estrogenic, androgenic, progestational, and adrenocortical steroid hormones in body fluids of mature intact Sprague-Dawley female rats was increased by s.c. implantation of 5 to 7 mg NaCl pellets containing 1 to 20% steroid 48 hr before administration p.o. of either 7,12-dimethylbenz(a) anthracene or procarbazine. The incidence of rats developing one or more mammary carcinomas in each treated group was compared to that ovserved in simultaneously treated groups receiving only the carcinogen, steroid, or no treatment whatsoever, with weekly observation of all rats until palpably growing tumors were biopsied and proven carcinomatous or until death occurred from other causes determined by autopsy. A total of 105 untreated or steroid-implanted rats followed to death (234 to 256 days median observation) developed no breast carcinomas. Rats fed either of the carcinogens developed initial evidence of breast carcinoma, after 136 to 156 days median observation, in 51 to 57% of 318 total treated rats. Nonbreast carcinomas and sarcomas developed in 5 to 10% of the carcinogen-treated rats.

Animals↗
PubMed1999

Progestational effects of combinations of gestodene on the postmenopausal endometrium during hormone replacement therapy.

OBJECTIVE: The aim of the study was to assess the dose-response effects on the postmenopausal endometrium of 3 sequential combined hormone replacement regimens and 1 continuous combined hormone replacement regimen of estradiol and gestodene. STUDY DESIGN: In this 2-year double-blind, placebo-controlled study, 278 healthy postmenopausal women received either 2 mg estradiol sequentially combined with 50 microg or 25 microg gestodene, 1 mg estradiol sequentially or continuously combined with 25 microg gestodene, or placebo. RESULTS: All 4 hormone treatment regimens produced a safe endometrial histologic appearance. The regimens that were based on the lower dose of 1 mg estradiol was associated with less uterine bleeding than were those that were based on 2 mg estradiol. For sequentially opposing the 2 mg dose of estradiol, the dose of 25 microg gestodene was less efficient in producing secretory activity than was the dose of 50 microg gestodene. The measurement of placental protein 14 in serum reflected the secretory transformation of the endometrial buildup. CONCLUSION: The reduction in bleeding episodes associated with regimens with lower estradiol doses may lead to improved long-term therapy compliance by menopausal women. The potency of progestogens can be assessed by measuring the serum concentration of placental protein 14.

Dose-Response Relationship, Drug↗
PubMed1984

Endocrinological studies with (7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14).

A novel steroid, (7 alpha, 17 alpha)-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one (Org OD 14), is described which has concomitant weak estrogenic, progestational and androgenic activities. This hormonal profile was demonstrated using various endocrinological tests and the results were evaluated in terms of well-known reference compounds. It has been well established that combinations of estrogens, androgens and progestagens exert positive or synergistic effects on certain target organs, e.g. the hypothalamic-pituitary axis, and antagonistic or complementary effects on others, e.g. on the endometrium. Org OD 14 with estrogenic, androgenic and progestational activities can therefore be expected to induce complex effects on various target organs. This explains the observed effects of the compound on hypothalamic-pituitary axis, bone-loss, endometrium and sexual behaviour.

Anabolic Agents↗
PubMed1977

Effect of short-term cyclic administration of cyproterone acetate on pituitary-ovarian function in the human.

Short courses of cyproterone acetate, a compound with progestational and antiandrogenic activities, were administered to normally menstruating women during different phases of the menstrual cycle to suppress growth and maturation of the follicles and corpus luteum function. Postovulatory administration of 20 mg of the drug daily for 8 days to two women delayed menstruation by 4 to 6 days, followed by prolonged bleeding and short post-treatment cycles. Plasma levels of progesterone were suppressed temporarily during therapy, but increased immediately after cessation of treatment. Administration of 10 mg of the drug for 8 days during the early follicular phase to two women resulted in irregular bleeding, short cycles, and decreased plasma levels of progesterone throughout the cycle. Reduction of the dose to 2.5 mg during the early follicular phase in two other women also resulted in irregular cycles. When the 2.5-mg dose was administered to three women from the 8th to the 15th days of the cycle, vaginal bleeding and cycle length were normal. Plasma levels of luteinizing hormone and progesterone were suppressed during therapy. In one subject, cervical mucus was found to be hostile to sperm penetration in all three treatment cycles. The results indicate that, with cyclic administration of low doses of cyproterone acetate to women during the late follicular phase, it may be possible to interrupt pituitary-ovarian function, as well as sperm transport through the cervical mucus.

Body Temperature↗