Progestins for the prevention of spontaneous preterm birth: review and implications of recent studies.

Progesterone plays a central role in the mechanisms of parturition in many species. Despite remarkable advances in our understanding of this hormone's mechanism of action, its roles in human pregnancy maintenance and parturition are not fully appreciated. Proper scientific hypothesis testing of progestins to prevent preterm birth has been limited because of the issues that can plague interventional trials in obstetrics, including patient selection, choice of outcome and power. The largest studies enrolling patients with a history of prior preterm birth alone to prevent recurrence appear contradictory. In contrast, consistent evidence from one multinational trial and a secondary analysis of another suggests cervical length may serve to identify potential responders to this therapy. Finally, the safety of progestin administration is a legitimate concern and a meta-analysis justifies the need for further investigation of safety issues. This review presents recent findings regarding progestin therapy from both clinical and laboratory data and considers unresolved issues for use of these agents.

[Influence of anti-androgen therapy for prostatic hypertrophy on lipid metabolism].

Antiandrogen therapy has an important role in the treatment of patients with benign prostatic hypertrophy who lack indication for surgery. Herein, the effects on lipid metabolism of administration of antiandrogen agents for benign prostatic hypertrophy are reported. Eighty patients with benign prostatic hypertrophy were each treated with the antiandrogen agents, chlormadinone acetate, allylestrenol, gestonolone caproate and oxendolone for 12 months. The levels of total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), alpha-lipoprotein, apoprotein, and maronediardehyde (MDA) were measured every 4 weeks after initiation of antiandrogen treatment. In the chlormadinone acetate group, the TG level was significantly decreased between 3 and 6 months after treatment (p < 0.05). In the oxendolone group, the alpha-lipoprotein level was also elevated between 3 and 6 months and between 6 to 12 months after treatment (p < 0.05). The MDA level was also significantly elevated 6 and 12 months after treatment. However, the levels of the other lipids were within the normal range. In conclusion, the changes in the levels of plasma lipoprotein, apoprotein and MDA resulting from antiandrogen therapy were unlikely to be a cause of ischemic coronary disease.

[Pharmacological combinations in the treatment of benign prostatic hypertrophy]. / Associations pharmacologiques dans le traitement de l'hypertrophie prostatique bénigne.

In the development of the obstructive symptomatology of benign prostatic hypertrophy (BPH), two components may be identified, mechanical and dynamic. In the mechanical component, the interaction of a stromal and a epithelial compartment determines prostatic mass growth. The dynamic component involves smooth muscle tone in the prostate and urethra. The consideration that prostatic disease is not only epithelial in origin, but also stromal, leads to the association of an antiandrogen (which acts on the epithelial component) and an antiestrogen (active on the stromal component) in the medical therapy of BPH. In 1985 we carried out a randomized study on 256 BPH patients treated with Cyproterone acetate (CPA) plus Tamoxifen (TAM). Recently, we performed a multicenter double blind study on BPH patients treated with the association CPA plus Serenoa Repens. A statistically significant difference in prostate volume reduction between the groups treated with the combinations and those with the monotherapies was observed. The development of new compounds, such as 5 alpha reductase and aromatase inhibitors, consents to introduce a combination therapy with less side effects. A second pharmacological association may be obtained with drugs acting on the mechanical and others acting on the dynamic (alpha blockers) component of BPH. This combination may associate the early symptomatic effect of alpha blockers with the long term results of a 5 alpha reductase inhibitor, antiestrogen or aromatase inhibitor.

[Antiandrogen therapy of benign prostatic hyperplasia--review of the agents evaluation of the clinical results].

Various non-surgical therapeutic modalities such as balloon dilation of the prostatic urethra, hyperthermia of the prostate and medication with antiandrogens and/or adrenergic blockade have been attempted for the patients with benign prostatic hyperplasia (BPH) especially in an early stage or in a poor operative risk. The observation that androgen deprivation induces shrinkage of the hyperplastic prostate represents the basis for the treatment of BPH with antiandrogen. Although several antiandrogens are now in clinical use in our country, there still remain problems to be solved. We reviewed the mechanism of action and the clinical results of antiandrogens in the treatment of BPH. The improvement following antiandrogen therapy occurred among the patients with symptomatic BPH, in 50-80% subjectively and in 40-50% objectively. The therapy appeared to be more effective in an early stage of the disease. However, the limitation of the duration of the effects and unfavorable side effects should also be noticed. The progestational agents such as gestonorone caproate, chlormadinone acetate and allylestrenol suppress more or less sexual function by interference of the pituitary-gonadal axis. Besides, coincidental prostate cancer must be excluded since antiandrogen therapy might hinder the natural course of the cancer.

Active specific immunotherapy of renal cell carcinoma patients: a prospective randomized study of hormono-immuno-versus hormonotherapy. Preliminary report of immunological and clinical aspects.

Early results of a prospective, randomized trial of active, specific immunotherapy adjunctive to nephrectomy in all stages of RCC are presented. Forty-three patients with median followup of 30 m, who were randomly allocated to either immuno-hormonotherapy arm (IMT), or hormonotherapy alone (HT), are evaluated in terms of progression-free interval (PFI) and overall survival by life table method. Immunotherapy consisted of autologous irradiated tumor cells (AITC), admixed with bacillus Calmette-Guérin (Glaxo) administered by the intradermal and endolymphatic route. Clinical results of this study show only a trend for advantage of the experimental (IMT) arm over the control (HT) arm, this trend did not reach statistical significance level: prolongation of disease free period in stages I-III with localized disease (p less than 0.1) and prolongation of survival in patients with metastatic disease (p less than 0.07). A correlation was established between induction of cutaneous delayed hypersensitivity (DTH) to AITC and prolonged PFI and survival: patients with positive DTH had a significantly better course of disease than those who could not be converted to positivity after repeated immunizations. Positive in vitro leukocyte migration inhibition against autologous tumor preparations correlates well with positive in vivo cutaneous DTH. Some immunological aspects of active immunization with autologous tumor cells are discussed.

In vitro responsiveness of ovarian epithelial carcinomas to endocrine therapy.

As previously reported, ovarian epithelial carcinomas may respond to endocrine therapy. We examined the direct effect of progesterone, medroxyprogesteroneacetate, gestoneron, 17-beta-estradiol, tamoxifen, 4-OH-tamoxifen, or N-desmethyltamoxifen on the proliferative capacity of ovarian carcinoma cells by means of the colony assay described by Hamburger and Salmon. The growth rate of 25 tested tumors (ascitic fluid, primary tumor, metastases) was 68%. The plating efficiency was 0.078%. Beside the drug testing estrogen and progesterone receptor levels were determined. The inhibition of colony survival was slightest with 17-beta-estradiol, more pronounced with medroxyprogesteroneacetate, gestoneron, N-desmethyltamoxifen, and progesterone, and greatest with 4-OH-tamoxifen and tamoxifen. Significant and dose-dependent inhibition of greater than 70% was observed with tamoxifen and 4-OH-tamoxifen in 80% of the tested tumors. There was no significant correlation between the in vitro responsiveness and the level of hormonal act not only via an estrogen receptor but also via an antiestrogen-binding site.

Use of progestogens as an adjuvant to surgery in the treatment of stage I adenocarcinoma of the uterine corpus.

Fifty-nine patients with proven stage I adenocarcinoma of the uterine corpus were treated by total abdominal hysterectomy and bilateral salpingo-oophorectomy, followed by gestronal hexanoate intramuscularly for 3 months and then medroxyprogesterone acetate orally for a prolonged period. In the 7-year period of study, there were no vaginal recurrences, but one patient suffered a recurrence in the inguinal lymph nodes and pelvis. Undesirable side effects did not occur. These results compare favourably with other reported studies in which surgery and radiotherapy were used.

Pilot study with adjuvant hormone therapy in FIGO stage I endometrial carcinoma with myometrial invasion.

A pilot study with adjuvant hormone therapy in FIGO stage I endometrial carcinoma with myometrial invasion was carried out. All patients received total abdominal hysterectomy and bilateral salpingo-oophorectomy plus complementary radium therapy on the vaginal stump. After the conventional treatment, patients were randomly allocated to adjuvant hormone therapy or no further treatment. Hormone therapy consisted of gestonorone caproate (17 alpha-hydroxy-19-norpregn-4-en 3, 20 dione caproate) administered i.m. at the dose of 200 mg/week for 1 year. Of the 62 patients who entered the study, 51 were considered evaluable (24 with adjuvant hormone therapy and 27 with no further treatment). Five patients had a relapse: four of these were in the group with no further treatment. Actuarial relapse-free survival analysis at 5 years was 95.7% in the group of adjuvant-treated patients and 82.8% in the control group. Although there is no statistical significance, adjuvant therapy appears to result in an increase in relapse-free survival in the group of patients with deep myometrial invasion and undifferentiated carcinoma. Further studies are necessary to assess the effectiveness of hormone adjuvant treatment in FIGO stage I endometrial carcinoma with myometrial invasion.

The importance of gestagen, tamoxifen and steroid receptors in the therapy of endometrial cancer. Report of an experiment.

Six human endometrial cancers in different clinical stages were xenotransplanted into thymusaplastic nude mice. Estrogen and progesterone receptors in the tumor tissue were determined in each case. Two carcinomas with both estrogen and progesterone receptors showed a better clinical course and grew more slowly in nude mice than the four carcinomas with no receptors at all. Treatment with the antiestrogen Tamoxifen in the carcinoma with positive estrogen receptors showed a significant growth retardation compared with the control group. Estrogen treatment gave accelerated growth, whereas gestagen treatment showed no significant effect. The progesterone receptor content of the receptor-positive tumor tissue might have been too small. None of the four receptor-negative carcinomas showed any influence of tumor growth during endocrine therapy. The results demonstrate the importance of receptor determination as a prognostic sign and, further, allow the endocrine therapy of endometrial carcinomas to be complemented with Tamoxifen in estrogen-receptor-positive tumor tissue.

[Cystic glandular hyperplasia of endometrium associated with intramural adenomyosis - singular results following progestational therapy]. / Iperplasia ghiandolare cistica dell'endometrio associata con adenomiosi intramurale-singolare risposta con trattamento progestinico.

In this report Authors point out two singular cases of marked progestational changes of stroma and glands in adenomyotic foci. They were two 65 years' old women to whom gestonorone caproato was administered for cystic glandular hyperplasia of endometrium hystologically seen.

[Gestonorone therapy of prostatic adenoma]. / Uber die Behandlung des Prostaataadenoms mit Gestenoron.

Clinical trials with gestonorone led to favourable results in 65% of the patients. The drug is recommended particularly to patients in stage I or II of prostatic adenoma. It is justified to prescribe this treatment to high risk patients who cannot be operated because of their serious conditions. An objective assessment of the effect of the drug was possible by means of urodynamic and ultrasound tests which detected also fewer latent changes suggesting a continuation or repetition of the treatment.

The treatment of advanced cystadenocarcinoma of the ovary with gestronol and continuous oral cyclophosphamide.

Fifty-four patients with advanced cystadenocarcinoma of the ovary were treated with gestronol (Depostat), 200 mg/week, by intramuscular injection and continuous oral cyclophosphamide, the dose of the latter being varied to maintain the patient's white cell count at about 1.5 x 10(9)/l. A combined partial and complete remission rate of 76 per cent was obtained. The length of survival depended upon the type of remission and the type of remission was markedly affected by the amount of tumour removed at initial laparotomy.

Progeston therapy for menstrually related aphthae.

Ten female patients with a history of recurrent aphthous lesions for at least 5 years with the lesions occurring regularly in the latter half at the menstrual cycle were treated with progestogen in the form of an intramuscular depot injection. Medroxyprogesterone acetate and gestronol hexanoate was used. All 10 patients were satisfied with the treatment; the side effects were few.

[Monitoring the effectiveness of conservative treatment of benign prostatic hypertrophy by means of uroflowmetry]. / Untersuchungen zum Wirkungserfolg der konservativen Behandlung bei benigner Prostatahyperplasie durch Uroflowmetrie.

96 patients with benign hyperplasia of the prostate and dysuric complaints in stage I and beginning stage II were treated conservatively and medicamentously up to 12 months. In the collective of patients subdivided into 4 groups the conservative therapy was carried out in 3 groups with different phyto-preparations and in one group with gestonorone capromate. The voiding of the bladder was examined by means of uroflowmetry in intervals of four weeks before and after therapy. A clear success of the effect appeared only in the group of patients treated with gestonorone capromate. With phyto-preparations uroflowmetrically no significant effect on the disturbed voiding of the bladder could be established. The conservative treatment of the benign hyperplasia of the prostate should be carried out under uroflowmetrical control, in order not to miss the time of a necessary operative intervention.