Effects of Simvastatin and Combination of Simvastatin and Nylestriol on Bone Metabolism in Ovariectomized Rats.

We aim to compare the effects of simvastatin and combination of simvastatin and nylestriol on bone metabolism in ovariectomized (OVX) rats. Fifty healthy Wistar female rats were randomly allocated into 5 groups: sham + saline group (group A), OVX + saline group (group B), OVX + simvastatin (5 mg·kg·d) (group C), OVX + nylestriol (0.01 mg·kg·d) (group D), and OVX + simvastatin (3 mg·kg·d) + nylestriol (0.005 mg·kg·d) (group E). All mice were orally administrated with saline or medicine dissolved in saline for 10 weeks. Body weight of rats before and after the experiment was measured. Twenty-four hours after the experiment, calcium (Ca), creatinine (Cr), and hydroxyproline in urine were detected. Serum levels of osteocalcin (bone Gla-protein, BGP) and alkaline phosphatase (ALP) were measured. Bone mineral density was detected and trabecular bone was observed after the isolation of femur and tibia. Remarkably decreased serum BGP and increased serum ALP levels were detected in group B compared with those in group A. However, notably increased serum BGP and decreased serum ALP levels were found in groups C, D, and E compared with those in group B; femoral and tibial bone mineral density decreased in group B compared with that in group A, but increased in groups C, D, and E compared with that in group B. Simvastatin and combination of simvastatin and nylestriol promote formation of new bone, increase bone density, and improve bone microstructure damage in OVX rats.

The bioaccumulation and biotransformation of synthetic estrogen quinestrol in crucian carp.

The occurrence and fate of endocrine disrupting chemicals (EDCs) in aquatic species have attracted close attention during the last decades. In this study, the bioaccumulation and biotransformation of synthetic estrogen quinestrol, one of the typical EDCs, in the plasma and liver of crucian carp, were investigated by a newly developed and validated reversed-phase high performance liquid chromatography with fluorescent detection method. Crucian carp were exposed to quinestrol in concentration of 2, 10, 50, 100 µg/L (5.49, 27.43, 137.17, 274.34 nmol/L) for 60 days. After 60 days' exposure, the concentrations of quinestrol found in liver and plasma were in the range of 0.25-0.69 mg/kg and 0.19-0.30 mg/L respectively, positively correlated with the exposure concentrations ranged 2-100 µg/L (5.49-274.34 nmol/L). There was a negative correlation between the bio-accumulation ratios and the exposure concentrations of quinestrol. 17α-Ethinylestradiol was also found in liver and plasma, and the concentrations were 0.02-0.19 mg/kg and 0.37-0.96 mg/L, respectively. The results indicated that quinestrol can be accumulated and transformed to 17α-ethinylestradiol in crucian carp. Moreover, exposure to quinestrol caused oxidative damages to crucian carp and the content of malondialdehyde increased in all treatment concentrations.

[Effect of cyclooxygenase-2 on bone loss in ovariectomized rats].

OBJECTIVE: To investigate mechanism of cyclooxygenase-2 (COX-2) in bone loss in a postmenopausal osteoporosis (PMOP) rat mode with ovarietomy (OVX). METHODS: Forty female Sprague Dawley adult rats at age of 3 months were randomly divided into 4 groups, 10 in each group, including sham-operated (sham) group, OVX group, OVX treated with nilesteriol (OVX + E) group and OVX treated with aspirin (OVX + P) group. All rats in OVX, OVX + E and OVX + P groups underwent ovarietomy under abdominal anesthesia with 10% chloral hydrate. Rats in sham group were only taken with fat tissue with same weight under bilateral ovary. After surgery, penicillin was administered to prevent infection. At day 7 after surgery, agents were given by intragastric administration for 12 weeks. Nilestriol at 1.0 mg/kg was used in OVX + E group once a week, aspirin at 45 mg×kg⁻¹(×d⁻¹ was used in OVX + P group once a day. Saline with same volume was used in rats in sham and OVX groups. All agents were administered one time per day. Dose of agents were adjusted by weight per week. At end of study, bone mineral density (BMD) of right femurs and lumbar vertebrae 3-5 (L(3-5)) were measured. Morphology of bone was detected by hematoxylineosin, and expression of COX-2 was determined by immunohistochemistry staining. RESULTS: (1) BMD:BMD of right femur and L(3-5) was (0.209 ± 0.010) g/cm² and (0.230 ± 0.012) g/cm² in sham group and (0.181 ± 0.008) g/cm² and (0.201 ± 0.016) g/cm² in OVX group, which reached statistical difference (P < 0.01). BMD of right femur and L(3-5) was (0.203 ± 0.009) g/cm² and (0.224 ± 0.028) g/cm² in OVX + E group and (0.200 ± 0.011) g/cm² and (0.204 ± 0.003) g/cm² in OVX + P group, which were all higher than those in OVX group (P < 0.01, P < 0.05). However, there was no statistical difference in BMD between OVX + E and OVX + P group (P > 0.05). (2) Morphology of bone:bone trabeculae became fewer and degenerated in OVX group. However, bone trabeculae were regular and dense in OVX + P group and OVX + E group, which were similar to those in sham group. (3) Expression of COX-2:cells with COX-2 positive and expression of COX-2 around bone trabeculae in OVX group were more than those in sham, OVX + E and OVX + P group. CONCLUSION: COX-2 plays an important role in PMOP. Aspirin could prevent bone loss by decreasing COX-2 expression in OVX rats.

Combined effects of levonorgestrel and quinestrol on reproductive hormone levels and receptor expression in females of the Mongolian gerbil (Meriones unguiculatus).

The effects of treatment with a combination of levonorgestrel and quinestrol (EP-1; ratio of 2:1) on reproductive hormone levels and the expression of their receptors in female Mongolian gerbils were examined. We show that serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) decreased, whereas serum estradiol (E2) and progesterone (P4) increased after EP-1 treatment. EP1 down-regulated mRNA expression of the follicle-stimulating hormone receptor (FSHR) and the estrogen receptor (ER) ßin the ovary. EP-1 up-regulated the mRNA expression of the luteinizing hormone receptor (LHR) and the progesterone receptor (PR) in the ovary as well as ERα and PR in the uterus of Mongolian gerbils. The effects were time-dependent and dose-dependent. EP-1 had no obvious effects on ERα mRNA expression in the ovary. The current study demonstrates that the effect of EP-1 on the expression of ER subtypes is tissue-specific in Mongolian gerbils. EP-1 disrupted the reproductive endocrinology of the Mongolian gerbil. These findings suggest that the effects of EP-1 on reproductive hormone levels and their receptor expression in Mongolian gerbils may be the result of synergistic actions of levonorgestrel and quinestrol, with quinestrol playing the major role.

Inhibitive effects of quinestrol on male testes in Mongolian gerbils (Meriones unguiculatus).

The current study evaluated effects of quinestrol on oxidative stress and abnormal spermatogenesis for male Mongolian gerbils. Gerbils were randomly divided into multi-dose treated, single-dose treated, control groups. At 15 days after treatment antioxidant enzymes (SOD, GSH-Px) activities and T-AOC were decreased whereas the MDA concentration was significantly increased, testicular weight and seminiferous tubular areas decreased, germ cells were rarefied and showed irregular distribution in seminiferous tubules, apoptosis was pronounced among spermatocytes and spermatids, the number of dead and abnormal acrosomes of spermatozoa increased significantly in quinestrol treated groups. At 30 days following treatment the testicular histopathological changes were more severe, sperm quality and antioxidant capacity continued to decline, and multi-dose treatment produced more damage to gerbils testes compared with single-dose treatment. The physiological indicators were recovered by 60 days of treatment withdrawal. The results showed oxidative stress induced by quinestrol in relation to abnormal spermatogenesis.

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.

Low-dose hormone therapy in postmenopausal women in China.

OBJECTIVE: To review the experience of menopausal symptoms and low-dose hormone therapy (HT) in postmenopausal women in China. DESIGN: Literature review and critical summaries of available prospective, clinical trials (randomized, controlled trials, RCTs). RESULTS: Chinese women experience menopausal symptoms less frequently compared with women in developed countries, and the prevalence of menopausal symptoms is less in women of southern China than in women of northern China. The majority of postmenopausal Chinese women lack knowledge about HT, and the usage rate of HT is low in these women compared to that in women of developed countries. Some RCTs investigated the efficacy and safety of low- or ultra-low-dose HT, including conjugated equine estrogen, estradiol valerate, transdermal estradiol, nylestriol alone or in combination with progesterone, and tibolone in postmenopausal Chinese women. These RCTs reported that low- or ultra-low-dose HT relieved menopausal symptoms and prevented bone loss as well as standard-dose HT and was less likely to induce side-effects, including irregular vaginal bleeding and breast tenderness; there may be dose-dependent effects of HT. No study evaluated the effects of low-dose HT on cardiovascular events or breast mammographic density/risk of breast cancer. CONCLUSIONS: More RCTs are required to confirm efficacy and to assess the safety of low- or ultra-low-dose HT for a long-term period in a large group of postmenopausal women.

[Effects of pilose antler and antler glue on osteoporosis of ovariectomized rats].

OBJECTIVE: To observe the effects of pilose antler and antler glue on osteoporosis of ovariectomized rats. METHODS: 60 6-month-old female rats were divided randomly into sham-operated group, model group, the positive group, pilose antler high-dose group, pilose antler low-dose group and antler glue group. We extracted bilateral ovaries to establish osteoporosis model and treated at two weeks postoperationally for consecutively 13 weeks, then observed the effects of pilose antler and antler glue on rat bone mineral density, bone mineral content, serum biochemical indicators, bone tissue morphology and other indicators. RESULTS: After 13 weeks, the high-dose group and antler glue group could significantly improve the BMD and bone mineral content of the ovariectomized rats, reduce BGP and ALP content, and remarkably increase the width of trabecula bone and bone trabecula area percentage, increase osteoblasts significantly, and decrease osteoclast cells significantly. Pilose antler low-dose also had the phenomenon above, but the result was not so good as high-dose group. CONCLUSION: Pilose antler and antler glue can antagonize osteoporosis of the ovariectomized rats.

[Relationship between hormone therapy in women with ovarian malignancy and prognosis].

OBJECTIVE: To explore the relationship between hormone therapy (HT) in women with ovarian malignancy and prognosis. METHODS: HT was used in 31 patients with ovarian cancer after surgery, and 44 cases with ovarian cancer served as control. The expression of estrogen receptor (ER)alpha, ERbeta and progesterone receptor (PR) was detected by immunohistochemical staining respectively. The level of serum calcitonin and transforming growth factor alpha (TGFalpha) was detected by radio-immune and enzyme-linked immunosorbent assay pre- or post-surgery, as well as half a year to one year later post-surgery respectively in these cases. The survival curve of Kaplan-Meier and log-rank test as well as scale risk of Cox model were used to analyze the relationship between HT and prognosis of ovarian cancer. RESULTS: (1) The results of log-rank test showed that there was no difference in survival curve of patients with or without HT [(1108 +/- 52), (1086 +/- 43) d; P = 0.940]; the results of scale risk of Cox model also showed that HT was not an independent prognosis factor for patients with HT. (2) There was no relationship with HT and the accumulated survival in patients with either positive or negative expression of ERalpha, ERbeta and PR in tissue; as well as between HT and the level of serum TGFalpha pre-, post-surgery, or half a year to one year after surgery. (3) The level of serum calcitonin in patients without HT post-surgery half a year to one year later was higher than that pre-surgery [(141 +/- 13), (95 +/- 11) microg/L; P < 0.05], but there was no significant difference between patients with HT half a year to one year later post-surgery and pre-surgery [(90 +/- 18) microg/L, (93 +/- 14) microg/L; P > 0.05]. (4) There was a significant difference in body and emotion function between HT and without HT groups [(1.84 +/- 1.50), (1.45 +/- 0.82); (12.69 +/- 10.20), (12.90 +/- 11.61); P < 0.05], as well as in sex quality and autonomic nerve maladjustment and in the special list made [(1.05 +/- 0.74), (1.77 +/- 1.08); (10.10 +/- 3.21), (13.09 +/- 4.30); P < 0.05]. CONCLUSIONS: There is no adverse influence on prognosis in using of HT for patients with ovarian cancer after surgery. HT for patients with ovarian cancer post-surgery can help keep a stable level of serum calcitonin as well as improve the quality of life.

[Protective effect of estrogens replacement on apoptosis cells of nasal mocosas in ovariectomized rats].

OBJECTIVE: To study the protective effect of nylestriol on apoptosis cells of atrophic nasal mucosas in ovariectomized rats and the difference between nasal drip and gastrogavage. METHOD: Sixty rats with atrophic rhinitis were divided into four groups at random (each with 15 rats): contrary group (Cg), ovariectomized group (Og), ovariectomized + nylestriol nasal drip group (ONNDg), and ovariectomized + nylestriol by gastrogavage (ONGg). Earlier apoptosis cells of nasal mucosas taken from nasal septum were measured with flow cytometry. RESULT: After being ovariectomized, the number of apoptosis cells of mucosas increased. In ONGg, the number of apoptosis cells of mucosas increased at 15 d after operation (P < 0.05), but it recovered at 30 d and 60 d after operation. In ONGg, the number of apoptosis cells of mucosas increased at 15 d and 30 d after operation (P < 0.05), but it recovered at 60 d after operation. CONCLUSION: Estrogen replacement by gastrogavage and via nasal drip have effects on protecting cells of mucosas from lacking of estrogen by decreasing apoptosis cells in ovariectomized rats. It might cost more time to get therapeutic effectiveness via nasal drip than by gastrogavage.

[Effects of long-term replacement therapy of compound nylestriol tablet or low-dose 17 beta-estradiol on the expression of nerve growth factor in OVX rat hippocampal formation].

OBJECTIVE: To determine the effects of long-term estrogen deficiency and replacement therapy of compound nylestriol tablet or low-dose 17 beta-estradiol on the expression of nerve growth factor (NGF) in rat hippocampal formation. METHODS: Fifty 7 month-old female Sprague-Dawley rats were randomly divided into 5 groups: normal control, sham operated (SHAM), ovariectomized (OVX), OVX plus 17 beta-estradiol (OVX/ERT), and OVX plus compound nylestriol tablet (OVX/NL) groups. Immunohistochemistry of NGF was used to quantitatively determine the levels of expression of NGF using cell counting and imaging system in ovariectomized rat hippocampal formation. RESULTS: The number and optical density of NGF-positive neurons of all hippocampal subregions and dentate gyrus in OVX rats were obviously lower than those of the normal control, SHAM, OVX/NL, and OVX/ERT rats. CONCLUSION: Long-term estrogen deficiency can lead to a decrease of NGF expression in hippocampal formation, while the replacement of low-dose 17 beta-estradiol or compound nylestriol tablet can equally preserve the expression of NGF to a normal level, showing a neurotrophic effect of estrogen.

Effects of different nylestriol/levonorgestrel dosages on bone metabolism in female Sprague-Dawley rats with retinoic acid-induced osteoporosis.

OBJECTIVE: To determine an optimal dosage combination for a nylestriol/levonorgestrel (NYL/LNG) regimen in the treatment of female Sprague-Dawley (SD) rats with retinoic acid (RA)-induced osteoporosis in order to examine the rationale of NYL/LNG use for postmenopausal women. METHODS: This study included two sets of experiments; one was designed to confirm the success of the RA-induced osteoporosis model involving 48 SD rats, and the other to determine the optimal dosage combination of NYL/LNG. In the second set of experiments, a total of 160 female SD rats at 7 months of age were randomly divided according to their basal body weights into 16 groups (10 in each). Treatment dosages of NYL and LNG were arrayed in a 2 factor-4 level (2(4)) factorial design, i.e., NYL level I (N1 0.015 mg/kg), level II (N(2) 0.05 mg/kg), level III (N3 0.15 mg/kg) and level IV (N4 0.5 mg/kg) and LNG level I (L1 0.005 mg/kg), level II (L2 0.015 mg/kg), level III (L3 0.05 mg/kg) and level IV (L4 0.15 mg/kg). For 14 d, 70 mg/kg/d RA was given intragastrically to establish the osteoporotic model and NYL and LNG were then administered in different dosages on alternate days over a 3 wk period. Subsequently, body weight, uterine weight, endometrial status, Bone mineral density (BMD), bone turnover, and morphometry as well as parameters of biomechanics, serum sex hormones and lipids and estrogen receptor-alpha expression were determined for these rats. RESULTS: Uterine weights at L2, L3, and L4 dosage levels were significantly lower than those at L1 (P < 0.05). Serum estradiol at N4 and progesterone at N2, N3, and N4 had decreased. Bone mineral density at distal tibiae (R5) in L and LA, and at proximal femora (R3) in L4 had increased. The peak loading of lumbar vertebrae at N3 was higher than that at N1, N2, and N4 dosage levels and that of femora higher at N3 than that at N1 and N4. Serum alkaline phosphatase (ALP) levels at N3, N4, L2, L3, and L4 dosage levels were lower than those at N1, N2, and L1 (P < 0.05). Moreover, there were lower levels of trabecular separation (Tb.Sp) at N3 and N4. The mineral apposition rates (MAR) at N2, N3, N4, L2, L3, and L4 were lower than those at N1 or L1. Bone formation rates (BFR) at L3 and L4 had significantly decreased as compared with that at L1. Levels of serum total cholesterol (TC) at N2, N3, and N4 were lower than that at N1 (P < 0.05). Marked squamatization of uterine endometrium with an increased expression of estrogen receptor (ER)-alpha was observed at N4. CONCLUSION: The dosage of 0.15 mg/kg NYL prevented bone loss, decreased bone turnover rate and increased the maximal loading of bone without obvious side effects in RA-induced osteoporotic rats. The addition of 0.015-0.15 mg/kg of LNG (L2-L4) reduced uterine weights and serum ALP levels. Overall results showed that 0.15 mg/kg of NYL in combination with 0.015 mg/kg of LNG produced beneficial effects on bone metabolism in RA-induced osteoporotic rats.

[The effects of progestin on the bone metabolism in postmenopausal women].

Thirty postmenopausal women, including 26 with history of hysterectomy and bilateral salpingooophorectomy due to uterine myoma and 4 with natural menopause without any diseases were randomly allocated into two groups. Fifteen subjects received medroxyprogesterone acetate (MPA) 10 mg twice daily for three months, the other 15 received both MPA 10 mg twice daily and cyclopentylethinyl estriol (CEE3) 5 mg once a month for three months. Fasting urinary calcium/creatinine (Ca/Cr) and hydroxyproline/creatinine (OHpr/Cr) ratio, serum calcitonon (CT) and alkaline phosphatase (AKP) concentrations were measured before and after treatment in all subjects. The results showed that in both groups, the fasting urinary Ca/Cr and OHpr/Cr ratio reduced significantly, while serum CT and AKP increased significantly after treatment. The changes of these parameters were not significantly different between these two groups. These data indicated that progestin alone appeared effective in preventing 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.

The treatment of postmenopausal syndrome by monthly oral doses of quinestrol.

Seventy patients between the ages of 37 and 59 suffering from the menopausal syndrome were included in a clinical trial and treated for a period of 6 to 18 months. Out of the seventy, 43 were suffering from spontaneous and 27 from surgical menopause. Forty of them were given 1 mg of quinestrol and 30 received placebo. The drug was administered orally in a one-tablet dose once a month. An improvement took place in 35 (87.5%) of the women receiving quinestrol but in only 15 (50%) of those receiving placebo. Among the patients with spontaneous menopause an improvement was seen in 22 out of 25 (88%) receiving quinestrol, compared with 9 out of 18 (50%) receiving placebo. Tolerance of the drug was good and most of the laboratory tests as well as blood pressure and body weight showed statistically non-significant changes. This kind of treatment is expecially suitable when daily intake is undesirable.

PIP: Use of small daily doses of quinestrol, a synthetic estrogen consisting of 3 cyclopenthyl-ether of ethinyl estradiol, has been reported to result in remission of postmenopausal symptoms in many patients. This study used quinestrol in 1 mg monthly oral doses in a group of women (N=70) suffering from the menopausal syndrome (43 from spontaneous and 27 from surgical menopause). 40 women received quinestrol 1 mg and 30 were given placebo. Of the 40 who were given quinestrol, 25 had spontaneous menopause and 15 were surgically induced. In the placebo group, 18 had spontaneous menopause and 12 were surgically induced. Treatment lasted from 6-18 months; none of the patients knew whether they had quinestrol or placebo. Blood samples were taken in 10 patients before treatment and 6 months later. As a whole, improvement was observed in 87.5% of the quinestrol-treated group, in contrast to 50% of the placebo-treated group. For women with spontaneous menopause, an improvement was observed in 88% of the quinestrol group and 50% of the placebo group. With respect to the effectiveness of quinestrol, no significant difference in the relief of symptoms was observed between the 2 groups (spontaneous and surgical menopause). Observed side effects were skin rash in 2 patients, thrombophlebitis in 1 patient, vaginal bleeding in 3 patients and nausea in 4 patients. It was concluded that quinestrol therapy is especially suitable in surgical menopause where substitutive therapy is indicated, as well as in cases where daily intake is not favored.

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.

Fundamental differences in the action of estrogens and antiestrogens on the uterus: comparison between compounds with similar duration of action.

In order to understand differences in the mechanism of action of estrogens and antiestrogens, it is essential to make comparisons between compounds with similar duration of action. Hence, in these studies, we compare the action of a long-acting estrogen (17alpha-ethinyl estriol-3-cyclopentyl ether, EE3CPE) and a long-acting antiestrogen (U-11,100AUA) on the immature rat uterus and analyze different dosage regimens (single and multiple injections) in studying the effects of these compounds on the uterine estrogen receptor and on uterine growth and sensitivity to estradiol. During the first 24 h, UA (50 microng) and EE3CPE (5 microng) evoke remarkably similar receptor distribution patterns and uterine wet weight increase; however, pronounced differences are seen with long-term, multiple injection regimens (every 12 or 24 h for 72 h). Such treatment with UA results in maintenance of high nuclear receptor levels and very low cytoplasmic receptor levels (ca. 10% of total), but no further increase in uterine weight, DNA or protein content, or total receptor content beyond 24-48 h. In contrast, multiple injections of EE3CPE produce not only a prolonged nuclear retention of receptor, but a progressive increase in total receptor content in the tissue and 35-50% of total receptor is cytoplasmic; uterine weight and DNA and protein content also continue to increase markedly above the 24 h level, and responsiveness to estradiol is maintained. However, regardless of whether the uterus continues to grow (as the EE3CPE) or stops growing after 24-48 h (as with UA), the receptor content on a cell basis is similar. Hence, uterine responsiveness to estradiol and continued uterine growth appear not to be related to the total content of receptor per cell, but rather are correlated with the cytoplasmic receptor level within the cell. As there is a continuous translocation of cytoplasmic receptor to the necleus in the growing uterus, the antagonistic action of antiestrogens appears to derive from their ability to effect a marked perturbation in the subcellular distribution of receptor, whereby very little of receptor (ca. 10%) is cytoplasmic, and further estrogen receptor accumulation (most likely synthesis) is blocked.

[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.

Controlled trial of bromocriptine, quinoestrol, and placebo in suppression of puerperal lactation.

2-bromo-alpha-ergocryptine (bromocriptine) in a dosage of 2-5 mg twice daily caused a rapid fall in plasma prolactin. It was more effective than either a single dose of 4 mg quinoestrol or a placebo in suppressing puerperal lactation, as judged by milk flow and the relief of breast pain and congestion. Patients who received quinoestrol were more comfortable than those who received placebo.