Oral exposure of rats to dienestrol during gestation and lactation: Effects on the reproductive system of male offspring.

This study was aimed at determining whether dienestrol (DIES) affects reproduction in male offspring of rats following oral maternal exposure during gestation and lactation. Pregnant rats were treated from GD 6 to PND 21. Animals received 0 (control-vehicle), 0.75, 1.5, 3.12, 6.25, 12.5, 50, 75 µg/kg bw/d of DIES. A control group -without vehicle-was also included. High DIES concentrations caused abortions at 75 and 50 µg/kg bw/d, while at 12.5 µg/kg bw/d had still miscarriages. Ten male rats per group were kept alive until PND 90 to ensure sexual maturity. Body and organ weights, anogenital distance (AGD) at PNDs 21 and 90, biochemical and sperm parameters like motility, viability, morphology, spermatozoa and resistant spermatid counts, and histopathology for sexual organs and liver were determined. An increase in organ weight (liver and sexual organs) and a decrease in AGD due to vehicle were found. A reduction of sperm motility and viability, and an increase of abnormal sperm morphology were caused by DIES, which provoked a dose-dependent prostatitis. Maternal exposure to DIES induced toxicity on the reproductive system of the male offspring, which could affect the capacity of fertilization.

[Functional state of calcitonin-producing cells of the female rats' thyroid as a result of experimental osteopenia therapy by graduated support loading combined with oestrogens and calcitonin injection].

Effects of graduated (2-hr.) support loading, synestrol and myocalcic on the thyroid C-cells was evaluated with the immunocytochemistry and cytomorphometry techniques. Graduated support loading was shown to partially recondition degraded functioning of C-cells. Synestrol injection suppressed the stimulating effect of support loading; myocalcic had a little effect on the C-cell activity. Simultaneous injection of two substances cancelled out the stimulating effect of support loading.

Replens versus dienoestrol cream in the symptomatic treatment of vaginal atrophy in postmenopausal women.

OBJECTIVES: This study was designed to evaluate the efficacy of Replens, a non-hormonal moisturizing vaginal gel, on symptoms of vaginal atrophy in postmenopausal women, in comparison with Dienoestrol (Cilag), an oestrogenic vaginal cream. METHODS: Thirty-nine patients were randomly allocated to either of the two treatments. Replens was given three times a week during the 12 weeks of the study, while Dienoestrol was administered daily during the first 2 weeks and thereafter three times a week. Vaginal dryness index, itching, irritation, dyspareunia, pH and safety were evaluated every week the first month and every month thereafter. RESULTS: Both treatments had a significant increase on vaginal dryness index as soon as the first week of treatment, and the hormonal compound was significantly better than the non-hormonal one. All symptoms such as itching, irritation and dyspareunia significantly decreased or disappeared without any difference between the two treatments. For pH, no significant difference was seen either in each group or between the two groups. No adverse events related with the two drugs were found. CONCLUSION: This study shows that Replens applied vaginally three times a week, is a full therapy for all symptoms of vaginal atrophy as well as local estrogen. No serious adverse event was related. Replens is an alternative treatment to local estrogen and perhaps a good complement of systemic HRT in patient suffering from vaginal dryness.

[The correlation of the hormonal and clinical effects in patients with prostatic cancer undergoing niftolid treatment in combination with low doses of synestrol]. / Koreliatsiia hormonal'nykh ta klinichnykh efektiv u khvorykh na rak peredmikhurovoï zalozy pry likuvanni niftolidom u poiednanni z malymy dozamy synestrolu.

Effects were studied of niftolide in tablets, 0.25 g on a three-times daily basis in combination with low doses of sinestrol, 5 mg intramuscularly within 24 h, on tumor growth, blood plasma content of luteinizing hormone (LH), testosterone (T) and testosterone-estradiol-binding globulin (TEBG) in 46 patients with prostate gland carcinoma, including seven patients with metastases. After treatment for three months, plasma T level decreased by 63%, that of LH by 53% whereas TEBG increased twice as much. The treatments were administered for as long as 10 months, with estrogen therapy being tapered to a dose of 3 mg daily. The above treatment schedule resulted in stabilization or partial regression of tumor growth in as many as 94.9% cases; also deserving to be noticed was improvement in the outflow of urine and alleviation of the pain syndrome. The clinical effect is believed to be due to pharmacological blockade of androgenic receptors in the tumor and its metastases as well as to antigonadotropic activity of estrogen and striking lowering of blood plasma free T.

[An experimental study of the antitumor activity of preparations in a model of prostatic cancer]. / Eksperimental'noe izuchenie protivoopukholevoi aktivnosti preparatov na modeli raka predstatel'noi zhelezy.

A trial of a newly developed experimental model of prostatic cancer showed its convenience in simulating clinical symptoms and response to treatment. The model is effective in the studies of anticancer drugs with various mechanisms of action with special emphasis on immunomodulators as a promising adjuvant modality.

Promotive effects of diethylstilbestrol, its metabolite (Z,Z-dienestrol) and a stereoisomer of the metabolite (E,E-dienestrol) in tumorigenesis of rat mammary glands pregnancy-dependently initiated with radiation.

Wistar-MS rats received whole body irradiation with 260 cGy gamma-rays at day 20 of pregnancy and then were treated with diethylstilbestrol (DES), E,E-dienestrol (E,E-DIES) or Z,Z-dienestrol (Z,Z-DIES) for 1 year. DES administration caused the highest incidence of mammary tumors with a concomitant reduction of gain in body weight. When E,E-DIES or Z,Z-DIES in pellet form was implanted, the incidence of tumors was significantly lower than that observed in rats treated with DES. To clarify the increased susceptibility to mammary tumorigenesis after DES administration we measured hormone levels in the serum of rats implanted with pellets containing derivatives of the synthetic estrogens. The serum prolactin concentration was significantly increased by DES administration. When E,E-DIES or Z,Z-DIES pellets were implanted the prolactin level was markedly reduced to 4.5% and 0.7% of that observed in DES-treated rats, respectively. In addition, the serum concentrations of estradiol-17 beta and progesterone in rats with Z,Z-DIES pellets were higher than those of rats with DES or E,E-DIES pellets. A large number of DES-induced mammary tumors were positive for both estrogen and progesterone receptors, but no tumors negative for both receptors were obtained. The findings suggest that DES acts directly on radiation-initiated mammary cells via binding with estrogen receptors and/or stimulates the secretion of prolactin from the pituitary glands.

[The mechanisms of the decrease in prostatic mass in rats during the administration of estrogenic preparations into the cerebrospinal fluid]. / Mekhanizmy snizheniia massy predstatel'noi zhelezy krys pri éndolikvornom vvedenii éstrogennykh preparatov.

Experiments on albino male rats have shown that the endoliquor administration of estrogens at low doses results in the inhibition of proliferative processes in the prostatic tissues comparable with that observed at the administration of doses two orders larger, and at the subcutaneous administration. A study of the possible mechanism of the observed phenomenon has shown that this effect is associated with the fact that in such a way of estrogen administration conditions are created for deeper inhibition of the production of gonadotropins by the adenohypophysis, and as a result of it a decrease in the androgen level is observed leading to the inhibition of proliferative processes in the prostatic tissues.

[Effect of sinestrol on the course of the myodystrophic process in progressive Duchenne muscular dystrophy]. / Issledovanie vliianiia sinéstrola na techenie miodistrofi- cheskogo protsessa pri progressiruiushchei myshechnoi distrofii Diushenna.

Therapeutic effect of sinestrol was investigated in 15 patients with progressive muscular dystrophy of Duchenne (PMDD) aged 7 to 10 years, at stage II of the disease. The drug was given orally 1 mg twice a day for 3 weeks. Control group consisted of 14 patients with PMDD aged 7 to 9 years. By the end of the course a several relief of motor constraint was noted in 10 patients with functional tests improved, tendon reflexes increased. The results of clinico-electromyographic investigation performed 6 months after the sinestrol withdrawal evidenced progressive course of the disease, though its rate was significantly lower in sinestrol-treated group. The treatment did not produce considerable changes in the baseline hormonal profile (gonadotropins, prolactin, sexual steroids).

Estrogen in the treatment of abnormal cervical mucus infertility.

The effects of intravaginal estrogen treatment on the cervical mucus and PCT were investigated in ten primarily infertile patients. The abnormal cervical mucus was the only demonstrable factor of their infertility. The duration of the infertility had ranged from 5-10 years. In four cases the percentual and progressive motilities of the spermatozoa improved and the number of spermatozoa rose in the PCT. Three of the patients conceived during the test cycle. In addition the effects of intramuscular estradiol-benzoate on the cervical mucus and PCT were investigated in clomiphene-treated patients. No differences were found between the test and the control cycle.

[Comparative study of the effectiveness of various doses of estrogens after their "central" and "peripheral" administration]. / Sravnitel'noe issledovanie éffektivnosti razlichnykh doz éstrogenov pri ikh "tsentral'nom" i"perifericheskom" vvedenii.

Experiments on male rats were made to study the effects of synestrol and diethylstilbestrol on the sexual organs. The drugs were administered subcutaneously and into the CSF. Diethylstilbestrol propionate produced the most potent inhibitory action on proliferative processes in the prostate. This inhibition was found to be the most demonstrable when the drug was administered into the CSF. During endo-CSF administration the dose of the hormone could be considerably decreased, with the inhibitory action on the target organs being unchanged and side effects on the animal body being minimal.

[Initial experience with ethinyl estradiol sulfonate (J 96) in the therapy of prostate carcinoma]. / Erste Erfahrungen mit Athinylöstradiolsulfonat (J 96) bei der Therapie des Prostatakarzinoms.

Ethinylestradiol sulphate (J 96) is a depot estrogen which in a dosage of 2 mg per week has clearly antigonadotropic effects and evokes a suppression of the free testosterone in bilaterally orchiectomized patients with carcinoma of the prostate. The good compatibility in oral application and the possibility for the controlled intake recommend its use for the long-term therapy of the carcinoma of the prostate.