A combined ligand and target-based virtual screening strategy to repurpose drugs as putrescine uptake inhibitors with trypanocidal activity.

Chagas disease, also known as American trypanosomiasis, is a neglected tropical disease caused by the protozoa Trypanosoma cruzi, affecting nearly 7 million people only in the Americas. Polyamines are essential compounds for parasite growth, survival, and differentiation. However, because trypanosomatids are auxotrophic for polyamines, they must be obtained from the host by specific transporters. In this investigation, an ensemble of QSAR classifiers able to identify polyamine analogs with trypanocidal activity was developed. Then, a multi-template homology model of the dimeric polyamine transporter of T. cruzi, TcPAT12, was created with Rosetta, and then refined by enhanced sampling molecular dynamics simulations. Using representative snapshots extracted from the trajectory, a docking model able to discriminate between active and inactive compounds was developed and validated. Both models were applied in a parallel virtual screening campaign to repurpose known drugs as anti-trypanosomal compounds inhibiting polyamine transport in T. cruzi. Montelukast, Quinestrol, Danazol, and Dutasteride were selected for in vitro testing, and all of them inhibited putrescine uptake in biochemical assays, confirming the predictive ability of the computational models. Furthermore, all the confirmed hits proved to inhibit epimastigote proliferation, and Quinestrol and Danazol were able to inhibit, in the low micromolar range, the viability of trypomastigotes and the intracellular growth of amastigotes.

[Effects of acupoint catgut embedding combined with auricular point pressure on menopausal syndrome of liver-kidney deficiency type and estradiol].

OBJECTIVE: To observe the efficacy differences between acupoint catgut embedding combined with auricular point pressure with beans and nilestriol on menopausal syndrome of liver-kidney deficiency type, and to explore their effects on estradiol (E2). METHODS: Sixty patients with menopausal syndrome of liver-kidney deficiency type were randomly divided into an acupoint stimulation group and a medication group, 30 cases in each group. The patients in the acupoint stimulation group were treated by acupoint catgut embedding at Taixi (KI 3), Sanyinjiao (SP 6), Shenshu (BL 23), Ganshu (BL 18) and Taichong (LR 3), combined with auricular point pressure at Gan (CO12), Shen (CO10), Neifenmi (CO18), Shenmen (TF4), Pizhixia (AT4); the treatment was given once a week for consecutive four weeks. The patients in the medication group were treated with oral administration of nilestriol, 1 mg, once a day, combined with oral administration of oryzanol, 20 mg, three times per day for consecutive four weeks. The clinical symptom score was compared between the two groups before and after treatment as well as in follow-up visit. The level of E2 was obserced before and after treatment, and the clinical effect was compared. RESULTS: (1) Compared before treatment, the clinical symptom score in the two groups was significantly reduced after treatment and in follow-up visit (all P<0.05); In follow-up visit, the clinical symptom score in the acupoint stimulation group was significantly lower than that in the medication group (P<0.05). The different value before treatment and at follow-up in the acupoint stimulation group was better than that in the medication group (P<0.05). (2) Compared before treatment, the level of E2 in the two groups were increased after treatment (both P<0.05); compared before and after treatment, the difference in the treatment group was significantly higher than that in the medication group (P<0.05). (3) After treatment, the total effective rate was 93.33% (28/30) in the acupoint stimulation group, which was similar to 90.00% (27/30) in the medication group (P>0.05). CONCLUSIONS: Compared with nilestriol, acupoint catgut embedding combined with auricular point pressure with beans could better improve clinical symptoms for patients with menopausal syndrome of liver-kidney deficiency type, and increased the level of E2.

[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.

[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.

Antiosteoporotic activity of Er-Xian Decoction, a traditional Chinese herbal formula, in ovariectomized rats.

The antiosteoporotic effect of a herbal formula, Er-Xian Decoction (EXD), in ovariectomized (OVX) rats model of osteoporosis was investigated. The rats were divided into Sham and OVX groups. The OVX rats were further sub-divided into four groups administered orally with water, nylestriol (1 mg/kg, weekly) or EXD (300, 600 mg/kg, daily) for 12 weeks. In OVX rats, the increases of body weight, serum BGP and ALP were significantly decreased by EXD treatment. In OVX rats, atrophy of uterus and descent of BMD were suppressed by treatment with EXD and nylestriol. In addition, EXD completely corrected the decreased concentration of calcium, phosphorus, and estradiol in serum observed in OVX rats. EXD also significantly increased biomechanical strength comparable to the Sham group. This was also confirmed by histological results that showed its protective action. The findings assessed on the basis of biochemical, bone mineral density, biomechanical, and histopathological parameters strongly suggested that EXD had a definite antiosteoporotic effect, which is similar to estrogen.

[Effect of nylestriol on bone remodeling in ovariectomized rats].

OBJECTIVE: To clarify the effects of nylestriol on microarchitecture and interleukin-6 (IL-6) mRNA expression in tibial bone in ovariectomized rats. METHODS: 30 female rats were randomly allocated into 3 groups: sham, OVX and nylestriol-treated group. Nylestriol-treated group were ovariectomized, then fed with nylestriol for 3 months and the bone mineral density (BMD) was measured in lumbar vertebra by dual energy x-ray absorptiometry. After sacrifice of the animal, bone histomorphometric parameters were measured to study the changes in bone microarchitecture, and RT-PCR was performed to detect the expression of IL-6 mRNA in bone tissue. RESULTS: BMD was significantly reduced, while IL-6 mRNA level elevated in the OVX group compared with the sham group. Static histomorphometric data showed that the trabecular bone volume, mean trabecular plate thickness and density were reduced while the mean trabecular plate space elevated remarkably in the OVX group in comparison with that in the sham group. As for dynamic parameters, trabecular osteoid surface, tetracyclin labeled surface and bone turnover rate were increased while osteoid maturation rate decreased significantly in the OVX group compared with the sham group. BMD, IL-6 mRNA expression and bone histomorphometric parameters were improved in nylestriol-treated rats. CONCLUSION: Nylestriol plays an important role in maintaining bone volume and improving bone microarchitecture by markedly inhibiting bone turnover and bone resorption, which might be to some degree attributed to reduced IL-6 expression.

[Compound nylestriol tablet to prevent bone loss in osteoporotic rats].

OBJECTIVE: To investigate the effects of compound nylestriol tablet (CNT), containing nylestriol and levonorgestrel with a ratio of 1:0.3) and its components on the osteoporotic rat model induced by retinoic acid (RA) and ovariectomy (OVX). METHODS: We randomly divided 144 female SD rats (aged 7-month-old) into 12 groups (12 in each). In addition, 120 female SD rats aged 4-month were randomly divided into 10 groups (10 in each). Three dosage levels of CNT (0.039, 0.117 and 0.39 mg/kg body weight, daily), nylestriol (NYL, 0.30, 0.09 and 0.03 mg/kg body weight, daily) and levonorgestrel (LEV, 0.09, 0.027 and 0.009 mg/kg body weight, daily) were designed to prevent the bone loss of the osteoporotic rat model induced by RA and OVX respectively. Serum total calcium (Ca), phosphate (Pi), ALP, triglyceride (TG), total cholesterol (TC), HDL-C, total body BMD, isolated left femoral BMD and femoral Ca, and Pi after ashing were determined. RESULTS: Osteoporotic models could be induced by RA (70 mg/kg body weightdaily given intragastrically for 14 days) or by ovariectomy; CNT and its components had the preventive effects on bone loss in both models; The preventive effect of CNT was dose-dependent and stronger than its components; Many observed markers showed us the levels of high and moderate CNT given to be the strongest, corresponding to an optimal choice of the moderate dose CNT about one tablet per week in adult women. CONCLUSIONS: CNT therapy can prevent the bone loss of RA-induced and OVX-induced osteoporotic rats, and its therapeutic and preventive effect is better than its components used alone.

[Renal protective effect of nilestriol in aged women with hypertension].

OBJECTIVE: To investigate the renal protective effect of nilestriol in aged hypertensive women. METHODS: Forty-one aged hypertensive women treated with antihypertensive drugs were randomly divided into two groups. The women in Group A (n = 21) received nilestriol, whereas those in Group B (n = 20) received a placebo for six months. Antihypertensive drugs were unchanged. Twenty-four healthy subjects were set as the normal control group. RESULTS: 1. Before the treatment, the levels of urinary transferrin (TRF), retinol binding protein (RBP), P-selectin, vWF, and ET-1 were significantly higher in the aged hypertensive women than those in the control group. 2. The levels of TRF and RBP significantly decreased in both Group A and Group B after the 6-month treatment, but these levels in Group A were significantly lower than those in Group B (P < 0.05). 3. The levels of P-selectin, vWF, and ET-1 in Group A were significantly lower than those in Group B (P < 0.05-0.01) after the treatment. CONCLUSION: 1. In aged hypertensive women treated with antihypertensive drugs, the renal function is still damaged; 2. Nilestriol can significantly decrease the levels of TRF and RBP; 3. The renal protective effect of nilestriol may be related to the protection of endothelin function and antithrombosis activity.

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.

[Relationship between sex hormone levels and blood calcitonin gene-related peptide/endothelin-1 in postmenopausal women with coronary heart disease].

OBJECTIVE: To investigate the relationship between sex hormone levels and blood calcitonin gene-related peptide/endothelin-1, and to evaluate the therapeutic effects of nylestriol. METHODS: Forty perimenopausal women without coronary heart disease (CHD) and 30 postmenopausal women with CHD were studied, and 30 postmenopausal women were divided into two groups and treated randomly with either 2 mg nylestriol or placebo. Serum 17 beta-estradiol (E2), testosterone (T), plasma calcitonin gene-related peptide (CGRP) and endothelin-1 (ET-1) were measured. RESULTS: In postmenopausal women, serum levels of E2 and plasma concentrations of CGRP decreased, while serum levels of T and plasma concentrations of ET-1 increased; E2 was positively related to CGRP, and negatively related to ET-1; T was negatively related to CGRP or ET-1. In the nylestriol group, compared with the parameters before treatment, plasma CGRP increased and ET-1 decreased after treatment. CONCLUSION: Estradiol possesses certain effects on endothelial cell, which may be an important aspect of its protective effects.

[Roles of sex hormones and oxygen free radical in coronary heart disease].

To examine the roles of sex hormones and oxygen free radical(OFR) in coronary heart disease (CHD), the serum estradiol(E2), testosterone(T), SOD, MDA and lipid levels were measured in 44 postmenopausal women with CHD and 22 health women. Mean levels of T and MDA were significantly higher while mean levels of SOD and E2 were significantly lower in CHD group than those in control group. On relative analysis, there was a positive correlation between E2 and SOD, while a negative correlation was observed between T and MDA in CHD group. Eighteen postmenopausal women with CHD had been receiving nilestriol replacement therapy for 12 weeks. The serum SOD and HDL-C/TC levels increased significantly, but LDL-C and MDA decreased significantly. The overall data suggest that OFR plays an important role in CHD; Low E2 levels is a risk factor of CHD in postmenopausal women; Nilestriol replacement therapy can improve the metabolism of serum lipids and inhibit lipid peroxidation, therefore, it may be of benefit to postmenopausal women with CHD.

[Efficacy of Chinese recipes of replenishing kidney and activating blood circulation in female rats with osteoporosis induced by ovariectomy].

OBJECTIVE: To investigate the efficacy of Chinese recipe of replenishing Kidney and activating blood circulation (RKABC) in female rats with osteoporosis induced by ovariectomy. METHODS: Fifty female SD rats at 12 months of age were chosen, and were divided into 5 groups; control, model, model plus nylestriol, RKABC (high dose) and RKABC (low dose). The model of osteoporosis was established by ovariectomy in rats for 12 weeks, and then was given different kinds of liquid and administered approximately for 12 weeks. General bone mineral density (GBMD), femur bending strength (FBS), serum-BGP and urine-Hyp/Cr were measured. RESULTS: GMBD, FBS in 3 treatment groups were significantly higher than those in the model group (P < 0.05), but lower than those in the normal control group (P < 0.05); GBMD, FBS in 2 RKABC groups were slightly higher than those in nylestriol's group (P > 0.05). Compared with model group, levels of serum BGP in 2 RKABC groups increased (P < 0.05) and in RKABC (H) treatment group increased almost the same as those in the control group (P > 0.05). In comparison with model group, levels of U-Hyp/Cr in 3 treatment groups decreased (P < 0.05, P < 0.01) but 2 RKABC treatment groups still significantly higher than those in the normal control group (P < 0.05). CONCLUSION: It indicated that RKABC could control osteoporosis in female rats induced by ovariectomy and seems to promote bone formation.

[Study of nylestriol effect on bone histomorphometric parameters in ovariectomized rats].

OBJECTIVE: To investigate the response of trabecular bone of ovariectomized (OVX) rats to nylestriol. METHODS: Thirty-three female Wistar rats were randomly divided into three groups, 11 rats in each: nylestriol-treated group (E), OVX and the control (C). The OVX rats were used as a model for osteoporosis. After being fed with nylestriol for 3 months, all rats were sacrificed. The effect of nylestriol on bone microarchitecture and dynamics were studied by bone histomorphometry. RESULTS: The data suggest that trabecular bone volume, mean trabecular width, density and cortical thickness were remarkably reduced in OVX group (P < 0.05) while tetracycline labeled surface, osteoid surface and bone turnover rate were increased in comparison with that in C group (P < 0.05). The bone turnover rate and trabecular bone volume were improved with the treatment of nylestriol for 3 months in the OVX rats(P < 0.05). CONCLUSIONS: Trabecular bone volume and bone turnover rate can be improved by 3 month administrations of nylestriol in osteoporotic rat models.

[Relationship between sex hormone levels and blood lipids/immunity in perimenopausal women].

To investigate the relationship between sex hormone levels and blood lipids/immunity and to evaluate the therapeutical effects of nylestriol, 96 women without coronary heart disease(CHD) were studied during their perimenopausal period. The estimation of serum biochemical components included serum 17 beta-estradiol(E2), testosterone(T), total cholesterol(TC), triglyceride (TC), high density lipoprotein cholesterol(HDL-C), low density protein cholesterol(LDL-C), apolipoprotein A-I(ApoAI), apolipoprotein B(ApoB), lipoprotein (a)[Lp(a)], immunoglobulin G(IgG), and IgG antibody against cardiolipin(ACAIgG). Thirty-six postmenopausal volunteers were divided into two groups and randomized to treat with either 2 mg nylestriol or placebo. In postmenopausal women, serum levels of E2, E2/T, HDL, and ApoAI decreased, while those of T, TC, TG, LDL, ApoB, Lp(a), IgG, and ACAIgG increased. Serum level of E2 was positively correlated to HDL-C and negatively correlated to TC, ApoB, LDL, IgG, and ACAIgG. Serum level of T was positively correlated to LDL, IgG, and ACAIgG and negatively correlated to HDL. In the nylestriol group, as compared with the results before treatment, serum levels of TG, TC, LDL, IgG, and ACAIgG decreased and that of HDL-C increased after treatment. We conclude that estradiol is a protective factor of CHD, whereas testerone is a dangerous factor. After menopause, the imbalance of the estradiol/testosterone ratio increases the incidence of CHD. Nylestriol is an effective substitute for estradiol to prevent CHD in post menopausal women.

[Variation of female migraine after menopause and its prophylaxis and treatment].

320 cases of female migraine after menopause according to the diagnostic criteria were studied by using 1:1 matched analysis. It was found that the additional symptoms increased after menopause. Eighty cases available for follow-up were divided into two groups, on which the treatment tests were done. Each patient in group I took Nilestrioli 2 mg twice a month and Perphenazine 12 mg and Doxepin 75 mg per day, while each patient in group II took Tolfenamic acid 300 mg a day. Two months after treatment, the cure rates were 57.58% in group I and 27.78% in group II. Two monthes after the cessation of therapy, 2 cases had relapses in group I. These data indicate that the decrease of estrin disorder and the additional symptoms after monopause play important roles in the change of migraine physiology, and the corresponding treatment methods are rational.

[Effects of fructus cnidii coumarins compared with nilestriol on osteoporosis in ovariectomized rats].

AIM: To compare the total coumarins from dried fruits of Cnidium monnieri (TCCM) and nilestriol (Nil) against osteoporosis. METHODS: SD rats (40, female, 3-month-old) were randomly divided into basal control, age control, ovariectomized (Ova), Ova + TCCM 67 mg.kg-1, Ova + TCCM 200 mg.kg-1, 6 times a week, and Ova + Nil 1 mg.kg-1, i.g. once a week. After 12 wk, sections (20 microns) of proximal tibiae were examined histologically. RESULTS: Ova reduced markedly the trabecular bone mass due to bone resorption excessed bone formation (% Tb. Ar -59%). Treatment with TCCM 67 mg.kg-1 partly suppressed bone turnover, but did not inhibit bone loss in Ova rats (% Tb.Ar -43%). Treatment with TCCM 200 mg.kg-1 and Nil 1 mg.kg-1 increased the trabecular area (% Tb. Ar +100% and +274%). CONCLUSION: Nil was more potent than TCCM in protecting against osteoporosis in Ova rats via supression of bone turnover.

[Quantitative study on the effect of osthole on proximal tibiae in ovariectomized (OVX) rats].

Thirty-one 3-month-old Female Sprague-Dawley rats were randomly divided into 5 groups, basal control (group 1, killed at the begining), aging control (group 2), ovariectomized (OVX, group 3), OVX with nilestriol treatment group (group 4) and OVX with osthole treatment group (group 5). Group 2 and group 3 ig with water 5 ml.kg-1 and group 5 ig with osthole 6.7 mg.kg-1, all once a day for 6 d; group 4 ig with nilestriol 1 mg.kg-1, once a week. After 12 weeks, all rats were killed. The proximal tibiae of rats were processed to undecalcified sections at 20 microns thickness for histomorphometric analysis. OVX was shown to reduce markedly the trabecular bone mass (%Tb. Ar-59%) due to increase of bone turnover with the result that bone resorption exceeded bone formation, as compared with aging controls. In contrast, treatment of OVX rats with Osthole and nilestriol increased significantly the trabecular area (increased 68% and 27.1% compared with that of OVX respectively). Our results indicate that osthole and nilestriol treatment provides protection against osteoporosis in OVX rats. The protective mechanism of osthole and nilestriol involves supression of bone turnover, but the effects of osthole is lower than that of nilestriol (trabecular area decreased 55% more in osthole group than that with nilestriol treatment). Our finding may provide theoretical evidence for the clinical use of osthole or nilestriol for treatment and prevention of osteoporosis.

Nylestriol replacement therapy in postmenopausal women. A three-year prospective study.

A three-year prospective study was carried out in 283 postmenopausal women to evaluate the effects of a long-acting estriol derivative-nylestriol. The women were randomly assigned into 3 groups: group A (136 cases, nylestriol 2 mg/2 wk), group B (97, nylestriol 1 mg/2 wk) and group C (50, placebo/2wk). LDL-C decreased and HDL-C increased after 3 months of medication (P < 0.05), but TC and TG not significantly changed in any group (P > 0.05). No changes of lipids were found in group C (P > 0.05). Serum ALP, Ca/Cr and Hpr/Cr in fasting urine decreased in 3 months in both group A and B (P < 0.05), but not in group C (P > 0.05). Forearm bone mineral content loss was restrained in groups A and B (P > 0.05), but decreased markedly in group C (P < 0.01). The Kupperman index scores decreased by about 50% after 3 months and 80% in 12 months in groups A and B. Nylestriol induced mild stimulatory effect on the uterine endometrium, and addition of 6 mg of provera daily for 7-10 days every 6 months is recommended. Nylestriol exhibited no obvious effect on the breast. This study demonstrated that nylestriol can be used as an effective and acceptable estrogen replacement therapy for postmenopausal women.

[Prospective study on nylestriol replacement therapy in postmenopausal women].

A prospective study was carried out on 283 postmenopausal women to evaluate the nylestriol effect from Jan. 1989 to July 1992. Menopausal year ranged from 1-26 years. The women were divided randomly into three groups. Group A: the nylestriol were given 2 mg/2 weeks, 136 cases, group B: 1 mg/2 weeks, 97 cases, group C: placebo/2 weeks, 50 cases. The results showed: (1) High-density-lipoprotein cholesterol increased and low-density-lipoprotein cholesterol decreased in both group A and B (P < 0.05), but not in the placebo group (P < 0.05). (2) Both the group A and B had significant lessening of serum alkaline phosphatase, ratios of calcium to creatinine and hydroxyproline to creatinine (P < 0.05). (3) The mineral content of distal and proximal forearm bone remained unchanged in both group A and B (P > 0.05), but decreased significantly in placebos (P < 0.01). (4) The Kupperman index score in both group A and B decreased significantly in 3 month (P < 0.05). (5) Curettage were performed 205 times in group A and B. Histological diagnosis revealed neither carcinoma nor atypical endometrial hyperplasia. (6) No breast cancer was found. In conclusion, nylestriol is a convenient and acceptable drug which was beneficial for relieving climacteric syndrome, preventing osteoporosis and improving lipoprotein lipid pattern.