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 bone-protective effect of genistein in the animal model of bilateral ovariectomy: roles of phytoestrogens and PTH/PTHR1 against post-menopausal osteoporosis.

Genistein, a major phytoestrogen of soy, is considered a potential drug for the prevention and treatment of post-menopausal osteoporosis. Mounting evidence suggested a positive correlation between genistein consumption and bone health both in vivo and in vitro. Earlier studies have revealed that genistein acted as a natural estrogen analogue which activated estrogen receptor and exerted anti-osteoporotic effect. However, it remains unclear whether PTH, the most crucial hormone that regulates mineral homeostasis, participates in the process of genistein-mediated bone protection. In the present study, we compared the therapeutic effects between genistein and nilestriol and investigated whether PTH and its specific receptor PTHR1 altered in response to genistein-containing diet in the animal model of ovariectomy. Our results showed that genistein administration significantly improved femoral mechanical properties and alleviates femoral turnover. Genistein at all doses (4.5 mg/kg, 9.0 mg/kg and 18.0 mg/kg per day, respectively) exerted improved bending strength and b-ALP limiting effects than nilestriol in the present study. However, genistein administration did not exert superior effects on bone protection than nilestriol. We also observed circulating PTH restoration in ovariectomized rats receiving genistein at the dose of 18 mg/kg per day. Meanwhile, PTHR1 abnormalities were attenuated in the presence of genistein as confirmed by RT-PCR, Western blot and immunohistochemistry. These findings strongly support the idea that besides serving as an estrogen, genistein could interact with PTH/PTHR1, causing a superior mineral restoring effect than nilestriol on certain circumstance. In conclusion, our study reported for the first time that the anti-osteoporotic effect of genistein is partly PTH/PTHR1-dependent. Genistein might be a potential option in the prevention and treatment of post-menopausal osteoporosis with good tolerance, more clinical benefits and few undesirable side effects.

Production and radioprotective effects of pyrroloquinoline quinone.

Pyrroloquinoline quinone (PQQ) was produced by fermentation of the Methylovorus sp. MP688 strain and purified by ion-exchange chromatography, crystallization and recrystallization. The yield of PQQ reached approximately 125 mg/L and highly pure PQQ was obtained. To determine the optimum dose of PQQ for radioprotection, three doses (2 mg/kg, 4 mg/kg, 8 mg/kg) of PQQ were orally administrated to the experimental animals subjected to a lethal dose of 8.0 Gy in survival test. Survival of mice in the irradiation + PQQ (4 mg/kg) group was found to be significantly higher in comparison with the irradiation and irradiation + nilestriol (10 mg/kg) groups. The numbers of hematocytes and bone marrow cells were measured for 21 days after sublethal 4 Gy gamma-ray irradiation with per os of 4 mg/kg of PQQ. The recovery of white blood cells, reticulocytes and bone marrow cells in the irradiation + PQQ group was faster than that in the irradiation group. Furthermore, the recovery of bone marrow cell in the irradiation + PQQ group was superior to that in irradiation + nilestriol group. Our results clearly indicate favourable effects on survival under higher lethal radiation doses and the ability of pyrroloquinoline quinine to enhance haemopoietic recovery after sublethal radiation exposure.

[Effects of exercise and nilestriol on bone size and bone mass in ovariectomized rats].

OBJECTIVE: To investigate the influence of nilestriol (CCE3) and exercise on bone size and bone mass in ovariectomized (OVX) rats. METHODS: Forty eight (48) female Sprague-Dawley (SD) rats were divided randomly into six groups: (1) Normal control group, (2) Sham OVX group, (3) OVX group, (4) OVX + CCE3 group, (5)) OVX + exercise group, (6) OVX + CCE3 + exercise group. CCE (0.5 mg/kg per week) was given to the rats in OVX + CCE3 group and OVX + CCE3 + exercise group from the 2nd day after the operation for 11 weeks. Exercise training was loaded to the rats in exercise groups from the 7th day after operation, each rat was subjected to running on 0 dig angle runway with the speed of 16 m per minute, 45 minutes per day, 5 days per week for 10 weeks. RESULTS: The bone diameter, bone volume, bone wet weight, bone dry weight, bone ashes weight in the OVX group were lower than those in the sham OVX group (P < 0.01). All of these measurements were increased in OVX + CCE3 group and OVX + exercise group when compared with the OVX group, but were still lower than those in sham OVX group (P < 0.01). Exercise enhances the effect of CCE3 (P < 0.01). CONCLUSION: Exercise enhances the effects of CCE3 on the improvement of both bone size and quantity in OVX rats.

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.

[The estrogenic effect of formononetin and its effect on the expression of rats' atrium estrogen receptors].

OBJECTIVE: To observe the estrogenic effect of formononetin and its effect on the expressions of atrial estrogen receptor subtypes alpha and beta (ERalpha and ERbeta). METHODS: 50 femal rats were randomly divided into five groups: sham group, model group, nilestriol group, formononetin groups of low and high dose. Rats in sham group were cut a piece of fat before closing the abdomen, the others were ovariectomized. Vaginal exfoliated cell were observed from the fifth day to the tenth after operation to test if the model is successful. The sham and model group were given nomal saline in 10 mL/kg by gavage, the remaining three groups were given nilestriol 2.5 mg/(kg x w), low [20 mg/(kg x d) land high dose [100 mg/(kg x d)) of formononetin by gavage respectively. In the 8th week, vaginal exfoliated cell were observed, then decapitated the rats, removed the uterus, weighed and take wright staining microscopy. The relative expressions of ERalpha and ERbeta of right atrium were detected by RT-PCR. RESULTS: The vaginal cells exhibit a change of estrus after had been fed with high dose of formononetin after 8 weeks. Formononetin increase the uterus coefficient and the expression of atrial ERbeta (P < 0.01), but it dose not have any effect on the expression of ERalpha (P > 0.05). CONCLUSION: Formononetin have estrogenic effect in ovariectomized rats, and it can markedly upregulate the expression of rats' atrial ERbeta.

[Effect of nylestriol and levonorgestrel on the expression of estrogen receptor subtypes in human osteosarcoma MG-63 cell lines].

OBJECTIVE: To observe the effect of different concentrations of nylestriol (NYL) and levonorgestrel (LNG) on the expression of ERα and ERß in human osteoscarcoma MG-63 cell lines, and to explore the impact of paracrine effect on the gene expression. METHODS: MG-63 cells were treated with 3 concentrations (10(-10),10(-8), and 10(-6) mol/L) of NYL or LNG. The untreated control group and the positive control group were also established. The 2 groups treated with NYL (10(-10) mol/L) or LNG (10(-8) mol/L) were designed to renew the medium every 12 h. Semi-quantitative RT-PCR was conducted to detect the mRNA expression of ERα and ERß on the MG-63 cells treated with different concentrations of the 2 drugs, respectively. RESULTS: Both drugs up-regulated ERα and ERß mRNA expression. The best concentration for both NYL and LNG was 10(-6) mol/L for ERα expression. As for ERß, the best concentration of NYL and LNG was 10(-10) mol/L and 10(-8) mol/L. The role of medium replacement on the expression of ERα was not observed, but medium replacement inhibited ERß expression. CONCLUSION: Both NYL and LNG can up-regulate the mRNA expression of ER subtypes in MG-63 cells, with mutual restriction between the 2 subtypes. The paracrine effect on MG-63 cell lines may be involved in the regulation process of mRNA expression of ERß.

Establishment of an HPLC identification system for detection of counterfeit steroidal drugs.

A set of simple HPLC methods employing UV detection were developed for detection of counterfeit drugs by the qualitative and quantitative analysis of nine steroidal drugs, ethinylestradiol, diethylstilbestrol, norethisterone, norgestrel, methyltestosterone, medroxyprogesterone acetate, progesterone, testosterone propionate and nilestriol. The methods were based on studies of the relationships between the retention factors (k) of the nine compounds and the percentages of water to methanol in the mobile phases on a reverse phase Alltima C(18) column giving reliable separation of the compounds under three sets of chromatographic conditions. The methods were validated using statistical tests and were used on nine commercial samples for detection of possible counterfeit drugs.

[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.

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 Gengnianchun Recipe on bone mineral density, bone biomechanical parameters and serum lipid level in ovariectomized rats.

OBJECTIVE: To observe the effect of Gengnianchun Recipe (GNC) on bone mineral density (BMD), bone biomechanical parameters and serum lipid level in the bilaterally ovariectomized (OVX) rats and to explore the prophylactic and therapeutic action of GNC on ovariectomy induced osteoporosis and hyperlipidemia. METHODS: OVX SD rats, 10 - 12 months old, were divided into different groups and fed with GNC 2 g/d, GNC 1 g/d and Nilestriol 0.125 mg/week, respectively for 4 months to observe the change of BMD and bone biomechanical parameters of the lumbar vertebrae, and the serum levels of total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and to compare the effect of the two drugs on the morphology of the uterus. RESULTS: There was marked reduction in BMD and biomechanical parameters in lumbar vertebrae (P < 0.01) and increase of serum TC and LDL-C levels (P < 0.01) in rats after OVX. GNC or Nilestriol significantly improved the decreased BMD and biomechanical parameters of the lumbar vertebrae (P < 0.05 or P < 0.01), and reduced the serum TC and LDL-C levels (P < 0.01). In the Nilestriol group, the wet weight of uterus got increased obviously (P < 0.01), the number of uterine glands increased, uterine columnar epithelium thickened, and the mitotic figures in the epithelial stroma and myointimal cells augmented. But no such effect in wet weight and morphology of uterus was found in the GNC group. CONCLUSION: GNC could increase the BMD and biomechanical parameters of the lumbar vertebrae, reduce the serum TC and LDL-C levels, yet produce no adverse reaction in stimulating proliferation and hypertrophy of uterus.

[Protective effect of purariae isoflavone on apoptosis cells of nasal mocosas in ovariectomized rats].

OBJECTIVE: To study the protective effect of purariae isoflavone on apoptosis cells of atrophic nasal mucosas in ovariectomized rats. METHOD: 60 rats were divided into four groups as control, ovariectomized, ovariectomized + nylestriol (O + N) and ovariectomized + purariae isoflavone (O + P), each with 15 rats. Earlier apotosis cells of mucosas taken from nasal septum were measured with flow cytometry. RESULT: Compared with control group, and the number of apoptosis cells of mucosas increased after being ovariectomized,and the number of apoptosis cells of mucosas in O + N and O + D group didn't change. CONCLUSION: Nylestriol and purariae isoflavone might have effects on protecting cells of mucosas from lacking of estrogen by decreasing apoptosis cells in ovariectomized rats.

Effects of OsteoKing on osteoporotic rabbits.

Heng-Gu-Gu-Shang-Yu-He-Ji, also known as OsteoKing, is used as a herbal Traditional Chinese Medicine for the treatment of bone disease, including femoral head necrosis and osteoarthritis. However, whether OsteoKing has anti-osteoporotic properties has remained to be elucidated. The purpose of the present study was therefore to investigate the effects of OsteoKing on ovariectomy-induced osteoporosis in rabbits. Female New Zealand white rabbits were randomly divided into an ovariectomized (OVX) group and a sham-surgery group. The rabbits in the OVX group were subjected to an ovariectomy, while the rabbits in the sham group were subjected to the removal of an area of fat near the two ovaries. Bone mineral density, mechanical properties, serum biochemical parameters and micro-architecture were examined at 150 days post-OVX to characterize the experimental animal model. Once the osteoporotic rabbit model had been established, the rabbits in the OVX group were divided into the following groups: Model group, nilestriol group and 300 and 600 mg/kg OsteoKing groups, containing 16 rabbits in each group. OsteoKing and nilestriol were administered orally. The bone mineral density, mechanical properties, serum biochemical parameters, histology and micro-architecture were examined using dual-energy X-ray absorptiometric analysis, mechanical assessments, enzyme-linked immunosorbent assays, histopathological evaluation and micro-computerized tomography examination following 60 days and 120 days of treatment, respectively. Treatment with OsteoKing led to an elevation in the bone mineral density of the vertebra and serum phosphorus levels, reduced serum concentrations of osteocalcin, procollagen type I N-terminal peptide, tartrate-resistant acid phosphatase 5b and cross-linked N-telopeptide of type I collagen, improved mechanical properties (maximum load, stiffness and energy absorption capacity), and micro-architecture of the lumbar vertebra in the OVX osteoporotic rabbit model following treatment for 120 days. In conclusion, it was demonstrated that OsteoKing is effective in the prevention of estrogen deficiency-associated bone loss and may be a promising drug for the treatment of post-menopausal osteoporosis.

Estrogen stimulation of phosphatidylinositol metabolism in mouse uterine tissue.

The effect of estrogens on incorporation of labeled precursor into inositol-containing phospholipids (PI) from ovariectomized mouse uterus was investigated. The results indicate that diethylstilbestrol (DES) a potent mitogen, stimulated incorporation of myo-[3H]inositol into uterine PI in 1-3 h, with maximal incorporation occurring at 6 h. This activity followed a dose-dependent increase, with a maximal effect at 5 micrograms/kg. Incorporation of radiolabeled phosphorous into the polyphosphoinositides was also increased in estrogen-stimulated uterine tissue. Studies using a weak uterotropic DES derivative, Z,Z-dienestrol, produced an early stimulation of the PI response comparable to DES. This activity was increased by Z,Z-dienestrol, with minimal estrogen receptor occupancy, and did not result in stimulation of DNA synthesis. These findings would suggest that uterine PI stimulation may not occur via an estrogen receptor-mediated mechanism related to tissue proliferation induced by estrogens.

Temporal relationships between hormone receptor binding and biological responses in the uterus: studies with short- and long-acting derivatives of estriol.

The temporal relationships between hormone receptor binding and early and late biological responses in the uterus were examined using estriol (E3), a weak estrogen, and several more long-acting estriol derivatives, namely ethinyl estriol (EE3), estriol cyclopentyl ether (E3CPE), and ethinyl estriol cyclopentyl ether (EE3CPE). Dose-response curves of 3-day uterotrophic assays indicate that biological potency follows the order EE3CPE greater than EE3 or estradiol greater than E3CPE greater than E3. After a single injection of 5 mug of compound, E3 elicits the early uterotrophic responses (increased uterine wet weight and 2-deoxyglucose phosphorylation at 2-6 h) but gives only weak stimulation of later uterotrophic responses (enhanced rates of 2-deoxyglucose phosphorylation at 20-24 h and increased DNA synthesis rate and uterine weight over a 72 h period). E3, EE3, and estradiol all elicit a rapid (maximal by 1/2-1 h) uptake of receptor into the nucleus and show an equivalent wet weight response at 3 h. After E3, nuclear receptor levels and uterine weight decline rapidly; however, after EE3 or estradiol, nuclear receptor levels decline less rapidly remaining at least two-fold above the control until 24-48 hr, and uterine weight also remains elevated for at least 48-72 h. EE3CPE elicits both the early (4 h) and later (20-24 h) waves of glucose metabolism, shows a prolonged effect on DNA synthesis rate, and shows the most dramatic and prolonged (beyond 72 h) maintenance of elevated uterine weight and high nuclear receptor (beyond 24 h). Thus, chemical modifications of the estriol molecule which result in a prolonged stimulation of uterine growth and metabolism also result in a long-term maintenance of hormone-receptor complex in the uterine nucleus. These studies give strong support to the concept that true uterine growth requires the direct and prolonged influence of the nuclear estrogen-receptor complex.

GLC determination of 17 alpha-ethynylestriol 3-cyclopentyl ether.

A rapid, sensitive, and accurate GLC method of analysis of a new estrogenic drug, 17 alpha-ethynylestriol 3-cyclopentyl ether, was developed. The drug and the internal standard, tetratriacontane, are dissolved in chloroform, and an aliquot is heated with N-trimethylsilylimidazole at 80 degrees for 30 min. The silylated sample is chromatographed using a column packed with 1% methyl vinyl silicone gum on Gas Chrom Q. Quantitation is achieved by computer calculation of the peak area ratios. The observed peak is the 16alpha,17beta-bistrimethylsilyl derivative of the new drug substance. The GLC method was applied to the quantitative determination of the estrogenic compound in a tablet formulation containing 25 mug/tablet.

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 double-blind study of CEE3 in peri- and postmenopausal women: effects on bone loss and lipoprotein lipids.

A prospective double-blind study was carried out in 136 women 0.5 to 21 years since menopause (YSM) in order to demonstrate the effects of a long-acting estriol derivative-Nylestriol (CEE3) on bone loss and lipoprotein lipids. They were orally administered at 2 mg of CEE3 or placebo every 2 weeks. Among 90 subjects who finished 1 year of medication, 49 received CEE3 and 41 placebo. The results were: 1. Serum ALP, Ca/Cr and Hop/Cr in fasting urine decreased in 3 months (P < 0.05); 2. Menopause-related reduction of forearm bone density was restrained; 3. LDL-C decreased in 3 months and HDL-C increased in 6 months (P < 0.05), with no significant changes in TC and TG; 4. Side effects were mild. 1/3 of those with intact uterus had spotting and another 1/3 had moderate withdrawal bleeding after the addition of medroxyprogesterone acetate at the end of 12 months of CEE3 therapy. This study demonstrates that CEE3 is effective and acceptable for preventing osteoporosis and lipoprotein lipids disorder in postmenopausal women. Long-term application awaits further studies.

[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.

[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.