Quinestrol treatment induced testicular damage via oxidative stress in male Mongolian gerbils (Meriones unguiculatus).

The hypothesis that quinestrol exerts testicular damage via oxidative stress was investigated in male gerbils using a daily oral gavage of 3.5 mg/kg body weight for 2 weeks (the multidose-treated group) or 35 mg/kg body weight (the single-dose-treated group). The testicular histological morphology, antioxidant capacity and malondialdehyde (MDA) concentration in testicular tissue and plasma were assessed at 15, 30, and 60 days following treatment. The results showed that the activity of the antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxide (GSH-Px), and total antioxidant capacity (T-AOC), at 15 days after treatment in testicular tissue decreased, which led to the MDA concentration increasing while at the same time germ cells were rarefied and showed an irregular distribution in seminiferous tubules of quinestrol-treated gerbils. At 30 days, the testicular weight and antioxidant capacity continued to decrease, while the MDA concentration continued to increase, and testicular histopathological changes were more pronounced. Single-dose and multidose drug treatment had a similar effect on the antioxidant enzymes and MDA, but testicular damage was relatively severe at 15 and 30 days after multidose treatment. By 60 days of treatment withdrawal, however, the above parameters recovered to control levels. The results show that quinestrol causes reversible damage to gerbil testes that might be caused by the oxidative stress and that multidose treatment has more effects on testicular damage compared with one-dose treatment.

The effect of low dose nylestriol-levonorgestrel replacement therapy on bone mineral density in women with postmenopausal osteoporosis.

OBJECTIVE: Recently our studies have shown that nylestriol in combination with levonorgestrel prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in retinoic acid (RA) induced osteoporotic rats. In addition to the animal experiments, we evaluate the effect of Compound Nylestriol Tablet (CNT) on bone mineral density (BMD) in women with postmenopausal osteoporosis. Compound Nylestriol Tablet, which contains 0.5 mg of nylestriol (cyclopentylethinyl estriol) and 0.15 mg of levonorgestrel per tablet, was authorized as a new anti-osteoporotic agent for clinical trial in postmenopausal osteoporosis. METHODS: One year's clinical observation was performed in 191 eligible patients who were randomly divided into two groups (A and B). In group A, 119 patients were treated for one year with CNT (one tablet per week) and in group B, 72 patients with placebo. Bone mineral density of lumbar antero-posterior spine (L1-L4), lateral spine, total hip and total forearm positions including radius+ulna at the ultra distal areas, mid areas, and one-third areas, were measured before and after treatment. Biochemical parameters and effects of CNT on uterus, and breast were observed. RESULTS: We found that patients treated with CNT had a significant decrease of bone loss in total forearm, including radius+ulna at the ultra distal, mid, and 1/3 areas compared with control subjects (all P < 0.05). An improved BMD tendency could be seen at the lumbar spine. There were no differences in the observed biochemical variables. No side-effects on uterus, or mammary glands observed. None of the patients had uterine bleeding or vertebral fractures during one year's CNT treatment. CONCLUSION: These data suggested that CNT is effective, safe and convenient in treating postmenopausal osteoporosis.

[Effect of nylestriol on postmenopausal uterine endometrium].

Curettage was performed in 139 postmenopausal women before as well as 6 months, 12 months and 36 months after Nylestiol (CEE3) therapy, for totally 205 times. It was found that CEE3 could induce endometrial proliferation and uterine breakthrough bleeding, much greater in women using 2 mg of CEE3 than in those using 1 mg. Ciliated cell were present in the proliferative endometrium after CEE3. The endometrial tissues obtained in curettage in women after 12 months' therapy was similar to that of 6 months' therapy. No more endometrium was obtained after 36 months' therapy. Provera were given for women who had proliferative endometrium after 6-12 months' therapy with CEE3 1-2 mg/2w. There were no changes of endometrium. This suggested that further study the interval and dosage of provera should be given with CEE3.

Increased risk for cancer of the breast due to previous medication.

Fifteen patients presenting one or more risk factors for cancer of the breast, who also received medication with prolactin-stimulating effects, were selected. The medication was by hormone derivatives or by non-hormone drugs used for processes other than oncologic . In all cases the medication was for long periods, three or more years, with the exception of one case, where the correlation with the unfavourable evolution of the cancer process was more evident. In patients presenting the classic risk factors for cancer of the breast, it is recommended to avoid the prescription of drugs having a prolactin-stimulating effect. The association of both circumstances (risk factors and prolactin-stimulating medication) is considered as an increased risk for cancer of the breast.

PIP: 15 patients presenting 1 or more risk factors for breast cancer who were also receiving medication with prolactin-stimulating effects were selected for study. The medication was hormone derivatives or nonhormonal drugs used for other than oncologic processes. In all cases, the medication was taken over a long period, 3 or more years, with the exception of 1 patient where the correlation with the unfavorable evolution of cancer was evident. In patients presenting the classic risk factors for breast cancer, it is recommended that drugs with a prolactin-stimulating effect be avoided. The association of both circumstances (risk factors and prolactin-stimulating medication) is considered an increased risk for breast cancer. (author's modified)

Clinical significance of compound quinestrol-caused glucose intolerance.

PIP: A series of 146 women taking compound quinestrol (CQ) was tested for glucose tolerance and insulin release to determine the effects of CQ on these parameters. 23 normal subjects (6 male and 17 female) and 12 diabetics (7 male and 5 female) were also tested and their results were compared with those from the CQ-taking women. The curves of glucose tolerance, insulin release, release index during different phases, and the immunoreactive insulin-blood glucose (IRI-BG) distribution were compared. In this series, the insulin release curve, 45-minutes-after-release index, and IRI-BG distribution of subjects on CQ approximated those of normals, but differ dramatically from diabetic subjects. The glucose intolerance which accompanied the more active insulin reaction caused by CQ seems to gradually ameliorate or revert to normal after CQ withdrawal, a phenomenon which does not occur in true diabetics. Hence, the glucose intolerance caused by CQ is due to the drug's effect on the metabolism of carbohydrates or of insulin.^ieng

Replacement estrogen therapy for menopausal vasomotor flushes. Comparison of quinestrol and conjugated estrogens.

Quinestrol, conjugated estrogens, or placebo was used to treat 156 patients with pernicious vasomotor instability in a prospective, double-blind, randomized, multiinvestigator trial. Vasomotor flushes were severe in approximately 80% of the cases and moderate in 20%, relatively equally distributed among the various drug groups. Both qinestrol and conjugated estrogens were significantly more effective than placebo in relieving vasomotor symptoms (by chi2 analysis, P less than or equal to 0.05). Greatest improvement was seen in the group receiving the higher once weekly quinestrol dosage of 0.2 mg followed by the group on the lower quinestrol dosage of 0.1 mg once weekly and the group on conjugated estrogens, 1.25 mg daily for 21 days on and 7 days off. No significant difference in relief of vasomotor flushes was shown between the active drug groups. No drug-related complications or side reactions of significance occurred. The results indicate that once weekly quinestrol is effective in relieving the vasomotor symptoms of the menopause. Either of two once weekly quinestrol regimens is an effective as conjugated estrogens given daily in a cyclic manner and therefore offers an alternative form of exogenous estrogen therapy.

[Hormonal limitation of lactation (author's transl)]. / Hormonale Hemmung der Laktation

A doubleblind study comparing the limitation of lactation and absence of side effects of the oral estrogen Quinestrol with an injected drug. The main point was limitation of lactation immediately following delivery up to the first period. Table 1 shows an analysis of results. The oral drug was better and called "very good" only in the immediate postpartum time. There was no significant difference in the second phase up to the first postpartum period. The interval between delivery and first period was 8 - 9 weeks s. table 2. There was no difference in the intensity of the first perio" s. table 3.

Effects of breast-feeding practice on the post-partum endometrium.

Inactive endometrial patterns occur frequently in the post-partum period and their occurrence is modified by the breast-feeding practice. An abnormal endometrium pattern, viz., cystic hyperplasia, may occur more frequently in non-lactating women and in patients using oestrogens, especially long-acting preparations, for lactation suppression. Post-ovulatory endometrial patterns in lactating women occur infrequently during the puerperium. The implications of these findings are discussed.

PIP: Fundal endometrial samples from 91 white and 64 South African blacks were examined to assess postpartum endometrial patterns in the 2 racial groups and in relation to the lactation practice. The difference in the proportions of breast-feeding at 6 and 13 weeks postpartum was 26.5% and 16% for the white group and 68.75% and 47.9% for the black group. Endometria were separated into ''active'' groups which included proliferative, secretory, or hyperplastic specimens and ''inactive'' groups which showed atrophic or hypoplastic features. The chi-square for the association of an inactive endometrial pattern with lactation was significant for both white and black subjects, particularly at 13 weeks. Cystic hyperplasia was found to occur spontaneously, particularly in nonlactators, and with greater severity in patients who had received a long-acting estrogenic agent (quinestrol) for lactation suppression.

[Contraceptive effect and tolerance of monthly oral doses of quinestrol (author's transl)].

PIP: 86 fertile women aged 18 to 37 were given 3.5 mg of Quinestrol monthly for a total of 457 cycles and were studied for the effectiveness and tolerance of this contraceptive. In order to induce periodic hemorrhage, 6 mg of the synthetic progestogen ethynodiol diacetate was added to the Quinestrol. Patients were advised to use an additional contraceptive during the first cycle. Only 1 pregnancy took place throughout the study and this occurred in the first month in a patient who had neglected to use another contraceptive during this time. Side effects, which included nausea and vomiting, were reported most often during the 1st month of treatment and became less troublesome as therapy continued. Exceptions were hypermenorrhea and spotting, which occurred more frequently during later treatment cycles. Ovulation was found to occur in 28% to 39% of the cycles, suggesting that the antifertility property of Quinestrol is not due solely to its inhibitory effect on ovulation.^ieng