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PubMedDate not supplied

[Synthetic progestogens (author's transl)].

Synthetic progestogens are divided into three major groups of steroids which derive from the basic steroid nucleus. Several routes of administration can be used. The characteristics (progestomimetic, progestational, and hormonal) of the different progestogens are variable. The different compounds are therefore of therapeutic value in specific indications. For some of these a study of the literature was carried out. We studied : anomalies of the menstrual cycle (involving chronology, menstruation...); the premenstrual syndrome with or without benign mastopathy ; menopause (premenopause and established menopause). The differences in the tolerance of the different compounds in use are recalled, in connexion with contra-indications and major and minor side-effects. The wide differences between the various compounds can make the choice of the less than right progestogen greater than difficult.

Female↗
PubMed2004

[Morphometric and histological evaluation of uterine leiomyomas treated with GnRH agonists or progestational agents].

Both gonadotropin-releasing hormone (GnRH agonists) and progestational agents are commonly used in order to reduce the size of uterine leiomyomas before surgery. So far, little is known about the histologic changes underlying such shrinkage mechanism. Probably the conflicting data on this subject are due to the qualitative and subjective methods used by most previous reports. In this study we analyzed 42 leiomyomas from patients treated with GnRH agonists (14 different patient samples), patients treated with progestational agents (14 different patient samples) and age-matched control patients (14 different patient samples), using qualitative (light microscope analysis) and quantitative (morphometric analysis by a specific software) methods. We assessed the following parameters: areas of necrosis, areas of hyalinization, vasal density, vasal thrombi, thickness of vasal walls, size of vasal lumina, cell density, maximum nuclear diameter, maximum cytoplasmic diameter, mitotic index on each sample. The analysis showed that leiomyomas from women treated with GnRH agonist exhibited broader areas of necrosis, greater cell density, and wider vasal lumina, while those from women treated with progestational agents exhibited thicker vasal walls than the other two groups, respectively. In conclusion, our results suggest that vasal wall changes are the basis of leiomyomas shrinkage after GnRH agonist therapy.

Adult↗
PubMed1989

[Effect of estroprogestative drugs on the secretion of corticoadrenal hormones].

Estro-progestative drugs (EPD) have been used for many years and multiple secondary effects have been reported concerning mainly the glucidic and lipidic metabolisms. Effects of EPD on steroid metabolism have also been described and the authors present a review of the literature on this subject. Particularly it appears that EPD affect: the glucocorticoid metabolism, with augmentation of total cortisol although not in its free-form (augmentation of transcortine), the adrenal androgens metabolism, with diminution of their circulating rates, the aldosterone metabolism with augmentation of its secretion. These biological constatations could help explaining some clinical features occurring with administration of EPD: diminution of hirsutism and/or acne, augmentation of body weight, appearance of hypertension.

Adrenal Cortex Hormones↗
PubMed1977

Induction of uterine protein synthesis by synthetic progestins.

The capacity of artificial progestins, each possessing a C-19 methyl group, to stimulate protein synthesis in the uteri of castrated New Zealand White rabbits was studied in an attempt to screen for this type of progestational activity. It is apparent that modifications of the 4-pregnen-3,20-dione molecule not only alter total protein production, but also effect changes in the synthesis of the uterine protein, blastokinin, in comparison with the effect of unaltered progesterone. This indicates that altering the molecular configuration of progesterone offers contraceptive potential through its ability to influence the preimplantation uterine environment.

Animals↗
PubMed1986

Treatment of endometriosis in monkeys: effectiveness of continuous infusion of a gonadotropin-releasing hormone agonist compared to treatment with a progestational steroid.

The use of a GnRH agonist or a progestational steroid (levonorgestrel) for the treatment of endometriosis in monkeys was compared. Four monkeys with spontaneous endometriosis were treated for 6 months with a continuous infusion of a GnRH agonist (25 micrograms/day). Five animals with surgically induced endometriosis were treated with the same agonist for 3 months. An additional group of five monkeys with surgically induced endometriosis was treated orally with levonorgestrel (1 mg/kg X day), while a final group of four monkeys served as untreated controls. During agonist treatment, the four monkeys with spontaneous endometriosis gained body weight and had a greater than 80% decline in cyst size (representing a decline in secretory activity). Monkeys with surgically induced endometriosis had almost total resolution of endometrial lesions during agonist treatment, which was maintained throughout a 4-month posttreatment period. After initial stimulation at the onset of the GnRH agonist infusion, serum LH, FSH, estradiol, and progesterone levels decreased to near the levels of detection, where they remained until treatment was terminated. In comparison, levonorgestrel reduced endometrial lesion size, but the monkeys did not resume normal cycles as early as those treated with the agonist. Levonorgestrel-treated monkeys had normal serum LH and FSH levels, but low serum estradiol and progesterone levels. The results of this study indicate that either continuous infusion of a GnRH agonist or administration of levonorgestrel is effective for treating endometriosis in monkeys. The hormonal data suggest that the GnRH agonist acts at the level of the hypothalamus and pituitary, whereas levonorgestrel acts at the ovarian level.

Animals↗
PubMed1987

Endometrial stromal sarcoma: a clinicopathologic study of 11 cases with determination of estrogen and progestin receptor levels in three tumors.

Eleven cases of endometrial stromal sarcoma were obtained from the files of Yale New Haven Hospital from 1969 to 1981 for clinicopathologic correlation and determination of the outcome after hormonal therapy with progestational agents. Histologically, nine of the tumors were classified as low grade stromal sarcomas, and two were of a high grade. All of the patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy as the main modality of treatment. Two patients received radiation, three adjuvant chemotherapy, two hormonal therapy (Megace 160 mg qd), three received no therapy at all, and the treatment is not known in one case. Two of the patients who received no therapy had recurrences and were placed on hormonal therapy. The remaining patient was a stage IV and died of disease 3 months after diagnosis. All four of the patients who were treated with hormonal therapy are alive, free of disease, or with stable tumor from 2 to 6 years after diagnosis. The presence of estrogen receptors (ER) and progestin receptors (PR) was demonstrated in the tumor in some of the cases; this may explain the sensitivity of this neoplasm to hormonal therapy.

Adult↗
PubMed1992

Endocrine profile in breast cancer patients receiving chemotherapy.

Cyclophosphamide and other alkylating agents suppress ovarian function in pre-menopausal women. However, endocrine details remain unknown regarding the influence of patients' age and obesity on CMF-induced hormonal changes. We studied changes in endocrine profile due to chemotherapy (CMF) in 70 pre-menopausal patients with axillary node positive, stage II and/or III breast carcinoma. Plasma levels of estrone (E1), estradiol (E2), androstenedione (A2), luteinizing hormone (LH), and prolactin (PRL) were determined on day 1 and 8 of each chemocycle for 12 cycles. After receiving therapy, 23% of the women continued to have regular menstrual cycles (non-amenorrheic group). In the remaining 77%, ovarian function was suppressed, as evidenced by the onset of amenorrhea within 0-11 months (amenorrheic group). The mean time to amenorrhea was 2.83 +/- 0.33 months (SE). The time required to develop amenorrhea inversely correlated to the patient's age. Both incidence of amenorrhea and time to amenorrhea remained unaffected by either patient's obesity or the timing of chemotherapy initiation in relation to menstrual cycle phase (progestational, follicular). Plasma hormone levels fluctuated widely in both groups during the first three chemocycles. During chemocycle months 4 to 10, in the amenorrheic group, plasma E1, E2, and P declined to their baseline levels with a concomitant rise in LH levels. At this time, E1, E2, and P levels were significantly lower in amenorrheics, despite menstrual cycle associated fluctuations in the non-amenorrheic group. Estrogens (E1 and E2) gradually declined further following the onset of amenorrhea in subsequent months. Further data analysis suggests that host age or obesity did not influence CMF-induced changes in the plasma endocrine profile.

Adult↗
PubMed1984

Modulation of uterine sensitivity to decidual induction in the rat by nicotinamide; challenge and extension of a model of progestational differentiation.

A recently constructed model describes pyridine nucleotide metabolism as a key target of progesterone action during early progestational differentiation of the uterus ( progestation ). The present study was designed to challenge this model. Using uterine sensitivity to decidual induction as a "whole animal" index of preimplantational differentiation, nicotinamide (NAM) was administered as a probe, to test the model's validity. Pseudopregnant rats received NAM in two injections (100 mg each, i.p.) during a 3-h interval at selected times between 1200 h on Day 2 and 1200 h on Day 4. Deciduomata were induced by intrauterine instillation of phosphate buffer between 1800 h on Day 3 and 1200 h on Day 5. Uterine sensitivity was measured indirectly as uterine weight, 5 days after induction. The effect of NAM was dependent upon the time of its administration. Maximal sensitivity (1200 h on Day 4) was not altered by injection of NAM at 1200 h on Day 2, but was inhibited by 60% following injection at 1200 h on Day 3. After this period, the inhibitory effect of NAM was diminished. When NAM was injected at 1200 h on Day 4, a slight, but significant, augmentation of sensitivity was measured. These responses were predicted by the model. A comparison of the effects of NAM with those of progesterone suggested a mechanism of action for the hormone during early progestation .

Animals↗
PubMed1981

Transmitter role of the luminal uterine epithelium in the induction of decidualization in rats.

Ovariectomized rats were given hormonal treatment mimicking progestational ovarian secretions. At maximal uterine sensitivity, the luminal epithelium was squeezed out of one or both horn(s) transected at the isthmus. Simultaneous bilateral scratching and saline injection induced virtually no response in stripped horns while contralateral intact horns exhibited a maximal decidual reaction (DCR). The luminal epithelium regenerated after ablation and a 65% DCR was again elicited after 9 days. The inability of de-epitheliated horns to decidualize was not overcome by intraluminal injections of the supernatant or sediment of the 60 000 g homogenate of epithelium, PGF-2 alpha, PGE-2, arachidonic acid or histamine. Detachment of the epithelium without removal also prevented DCR induction. These results indicate that the luminal epithelium is an obligatory transmitter of the stimulus to DCR and cannot be by-passed by trauma. Release of the appropriate epithelial message to the stroma requires local preservation of membrane relationships between both tissues.

Animals↗
PubMed1982

Changes in the pattern of endometrial protein synthesis during decidualization in the rat.

Ovariectomized rats were given hormonal treatment mimicking progestational ovarian secretions. At maximal sensitivity a decidual reaction was induced by scratching the endometrium. After incubation of tissue with [35S]methionine, proteins were extracted from decidualizing and control endometrium and submitted to two-dimensional polyacrylamide gel electrophoresis (pH range 5--7), followed by staining or autoradiography. A total of about 800 different peptides could be distinguished on the gels. By 24 h after the decidual stimulus the most prominent changes were the appearance of 4 new peptides (mol. wt 12 000, 25 000, 42 000 and 56 000) and the disappearance of 5 others (mol. wt 31 000, 35 000, 100 000, 110 000 and 140 000). This new pattern remained grossly unchanged up to 72 h after decidual induction.

Animals↗
PubMed2005

Metastatic low-grade endometrial stromal sarcoma of the sigmoid colon three years after hysterectomy.

A 49-year-old woman, who had undergone hysterectomy for low-grade endometrial stromal sarcoma (ESS) 3 years ago, presented with a 2-wk history of lower abdominal pain. Barium enema and sigmoidoscopy disclosed a polypoid submucosal tumor. Histopathologic features of biopsy specimens from the lesion were similar to those of the resected uterine ESS. Under the diagnosis of metastatic ESS of the sigmoid colon, sigmoidectomy was performed. Microscopic examination demonstrated dense proliferation of spindle cells with little nuclear atypia, which were sometimes arranged in whorled pattern around abundant arterioles. Mitotic count is below 1 in 10 high-power fields. Immunohistochemically, the neoplastic cells were strongly positive for vimentin, estrogen receptor and progesterone receptor but negative for alpha-smooth muscle actin, S-100 protein and CD34. Thus, a final diagnosis of low-grade ESS metastasis to the sigmoid colon was made. Her postoperative course was uneventful and hormonal therapy with progestational agents is entertained.

Colon, Sigmoid↗
PubMed1982

Cigarette smoke-induced cholesterol C-20, 22-desmolase inhibition in pregnancy.

In an attempt to demonstrate the physiological importance of cholesterol C-20, 22-desmolase regulation of pregnenolone formation in maternal cigarette smoking during pregnancy, the in vitro effect of cigarette smoke extract on corpus luteal and placental desmolase ability to cleave (26-14C) cholesterol to (14C) isocaproic acid, was studied. Using the reverse-isotope dilution technique, (14C) isocaproic acid was isolated and characterized. With the homogenates of corpora lutea of pregnancy (4 to 9 weeks gestation) the maximal inhibitory effect (98.3%) on desmolase efficiency became evident at equivalent of 4 cigarettes. In response to concentrations of the extract at 1/2, 1, 2 and 4 cigarette equivalents on the preparations of placentae (18 to 20 weeks gestation), a dose-dependent pattern of inhibitory effect was observed (29.1 to greater than 95.1%). These results are consistent with the interpretation that decreased supply of pregnenolone for the biosynthesis of progestational and oestrogenic hormones may be causally related to changes characteristic of cigarette-smoke induced pathologic state. It is suggested that similar studies directed towards alteration in biosynthetic capacity of steroidogenic enzymes may provide the basis for our understanding of molecular events initiated in response to the common insult.

Adult↗
PubMed1995

Endocrine therapy for benign prostatic hyperplasia in the 90's.

Endocrine therapy by means of castration for benign prostatic hyperplasia was introduced already in the middle of the 19th century. The technique was never popularized and was abandoned following the introduction of safe surgical techniques. In the second half of this century, small series of various endocrine treatments have been reported, mainly using progestational agents. The hormone dependency of the prostate is unique, since testosterone itself is not very active on the prostate cells but has to be converted to 5 alpha-dihydrotestosterone, which is almost ten times as effective an androgen in the prostate cell. By blocking this conversion, highly specific antiandrogenic effect will be obtained in the prostate but not in other organs of the body. The first 5 alpha-reductase inhibitor, finasteride, has proven effective in reducing prostate DHT. In large clinical trials, it has shown to reduce prostate size, improve urinary flow and reduce symptom score, statistically significantly better than placebo. The effect is sustained over at least 3 years. In a double-blind, randomized, placebo-controlled study over 2 years, patients were similarly improved in the finasteride group, whereas they deteriorated in the placebo group. This indicates that finasteride is able to halt the progression of the natural course of benign prostatic hyperplasia. Benign prostatic hyperplasia, generally believed to be a stromal disease, is potentially dependent on estrogens for its development. By blocking aromatization of testosterone to estrogen in the prostate cells, a hypothetical beneficial effect on the disease process should be gained. Results from phase II-studies have been promising. However, in placebo-controlled studies, aromatase inhibitors did not perform better than placebo.(ABSTRACT TRUNCATED AT 250 WORDS)

Androstenedione↗
PubMed2002

Hormone-like behavioral effects of levonorgestrel and its metabolites in the male rat.

Levonorgestrel (LNG), a contraceptive progestin, exhibits, besides its progestational activity, other hormone-like effects at the peripheral level. To assess whether LNG and its metabolites exert androgenic and/or estrogenic actions at the central nervous system (CNS), their effects on male sexual behavior in castrated rats were examined. LNG, 5alpha-dihydro LNG (5alphaLNG), and the 3alpha,5alpha- and 3beta,5alpha-tetrahydro derivatives of LNG (3alphaLNG and 3betaLNG, respectively) were administered for 3 weeks either alone (1000 microg/day) or in combination (300 microg/day) with 5alpha-dihydrotestosterone (DHT, 300 microg/day) or with estradiol-17beta (E(2), 5 microg/day). Copulatory behavior was assessed twice per week and sex accessory organs weights recorded at the end of treatments. LNG restored full copulatory behavior comparable to that of testosterone treated animals, although with a slight delay, whereas 5alphaLNG induced male sexual behavior in a significantly lower number of subjects. 3betaLNG and 3alphaLNG induced mounting but failed to restore intromission and ejaculation. Combined LNG+E(2) treatment fully activated mounting and intromission, but ejaculation was only partially restored. Combined 5alphaLNG+E(2) treatment and the combinations of 3alphaLNG or 3betaLNG with E(2) were significantly less effective, activating fewer intromissions and ejaculations. 3alphaLNG and 5alphaLNG, in combination with DHT, restored male sexual behavior. LNG, but not its metabolites, induced a significant increase on the weight of sex accessory organs. The overall results demonstrated that high doses of LNG induce a potent androgen agonistic behavioral effect and that its A-ring reduction diminishes this potency and enables a shift towards a weak estrogen-like effect.

Androgens↗