Phytoestrogens and Bone Metabolism / 대한골다공증학회지

Although most gynecologists had prescribed estrogen with or without progestin for their menopausal patients before the publication of Women's health Initiative (WHI) trial findings, only 35 to 40% of women ever started hormone therapy (HT) and many discontinued it, because of perceived side effects and discomfort. HT will not likely to be regularly prescribed in the future given the recommendations by several groups against long-term use for chronic diseases after the release of the findings of the WHI. Consequently, many postmenopausal women have turned to botanical dietary supplements containing phytoestrogen as an alternative to HT. Although there are numerous studies in the literature over the last decade trying to address the efficacy of phytoestrogens on bone health in animal models and in humans, the efficacy of phytoestrogens as bone-protective agents in vivo remains unclear. Differences in the bioactivities of individual phytoestrogens, differences in bioavailability and metabolism of phytoestrogens within different study populations, and imprecise reporting of the form and dose of phytoestrogens provided in intervention studies may have leaded to the disparity in study results. However, the preventive effect of phytoestrogens for bone loss is promising. This review discusses the effects of phytoestrogens on bone metabolism and their roles on the prevention and treatment of postmenopausal osteoporosis.

The short-term effect of black cohosh on vaginal atrophy and safety in postmenopausal women / 대한산부인과학회지

OBJECTIVE: To evaluate the short-term therapeutic effect of black cohosh on vaginal atrophy and safety in postmenopausal women. METHODS: A total of 80 postmenopausal women having moderate to severe degree of climacteric symptoms were randomly allocated to receive black cohosh combined preparation (n=40) or placebo (n=40) daily for 12 weeks. Fifty eight subjects completed this clinical study. The effect of black cohosh on vaginal atrophy in postmenopausal women was evaluated by measuring Maturation Value. Maturation Value was determined from vaginal smear at 0 and 12 weeks of treatment. Safety assessment included vital signs, physical examinations, adverse events, and routine laboratory parameters (hematology, biochemistry and urinalysis). It was carried out at the beginning, and after 4, 8, 12 weeks of treatment. RESULTS: The mean (+/-standard deviation) Maturation Value decreased 0.18 (0.47+/-0.32 to 0.29+/-0.23) in black cohosh group and 0.13 (0.43+/-0.30 to 0.30+/-0.21) in placebo group. There was no statistical difference in change of Maturation Value from the baseline between the groups after 12 weeks. No serious adverse events were seen. Adverse events were observed in 7 (17.5%) patients in black cohosh group and 6 (15%) patients in placebo group. Prevalence of the adverse events did not differ statistically in the two treatment groups. No significant effects were seen on blood pressure, heart rate, body temperature, physical findings and laboratory values. Black cohosh was well tolerated. CONCLUSION: Black cohosh did not exert estrogenic effects on the vaginal atrophy but appears to be a safe alternative medicine for postmenopausal short-term use.

Comparison of Anti-osteoporotic Medications and Alternatives / 대한산부인과학회지

Osteoporosis becomes a serious health threat for aging postmenopausal women by predisposing them to an increased risk of fracture. Conventional pharmacological options are available for osteoporosis therapy, including bisphosphonates, the SERM raloxifene, estrogens, clacitonin, and parathyroid hormone. Although alternative treatment regimens, such as phytoestrogens, herbals, and dehydroepiandrosterone (DHEA) also show beneficial effect on bone density and health, further study to determine optional formulation is needed. Several new drugs are available or are in clinical development.

The Effect of black cohosh with St. John's wort (Feramin-Q(R)) on climacteric symptoms: multicenter randomized double-blind placebo-controlled trial / 대한산부인과학회지

OBJECTIVE: Results of several recent randomized clinical trials and epidemiological studies casted many doubts about the validity and safety of conventional hormone therapy for postmenopausal women. More and more women want to try more natural and safe ways of treating their climacteric symptoms. Black cohosh combined with St. John's wort may be effective in climacteric symptoms alternative to hormone therapy. This multicenter randomized double-blind placebo-controlled prospective clinical trial was carried out to evaluate the effect of the combined preparation of black cohosh and St. John's wort, Feramin-Q(R), on the general climacteric symptoms, hot flushes and climacteric depression. METHODS: Total of 80 postmenopausal women having moderate to severe degree of climacteric symptoms were randomly allocated to receive Feramin-Q(R) (n=40) or placebo (n=40) daily for 12 weeks. Fifty eight subjects completed this clinical study. The primary endpoint, the relief of general climacteric symptom and hot flushes were evaluated by measuring Kupperman index and the secondary endpoint, the relief of climacteric depression by Beck Depression Inventory at 4 and 12 weeks of treatment. RESULTS: After 4 and 12 weeks of treatment, Feramin-Q(R) and placebo groups showed significant decline of Kupperman index and BDI scores compared with baseline scores, but Kupperman index and BDI scores between the groups were not significantly different at 12 weeks. The changes of BDI scores between the groups were different at borderline significant level (p=0.07). Hot flush scores of Feramin-Q(R) groups were significantly decreased after 12 weeks of therapy, which showed significantly different at borderline level (p=0.07) from that of placebo. There was no statistical difference in change of hot flush scores from the baseline between the groups after 12 weeks. Among the 45 postmenopausal women with moderate to severe hot flush, Feramin-Q(R) group showed significant decrease of hot flush scores, which was significantly different compared with placebo group at 12 weeks of therapy. There were more patients (86.4%) in Feramin-Q(R) group, who had much more improvement of hot flushes compared with placebo group (54.6%) (P=0.04). CONCLUSION: There were no significant differences between placebo and Feramin-Q(R) groups concerning the effect on general climacteric symptoms and depression but Feramin-Q(R) was significantly more effective than placebo in relieving of hot flush in postmenopausal women with moderate to severe hot flushes. Therefore Feramin-Q(R) seems to be effective alternative for moderate to severe hot flushes.

Transforming Growth Factor-alpha Regulation of Insulin-like Growth Factor-II, Insulin-like Growth Factor Binding Protein-1 and 3 secretion and Epidermal Growth Factor receptor expression in human luteinized granulosa cells / 대한산부인과학회잡지

OBJECTIVE: To investigate the effects of transforming growth factor (TGF)-alpha on insulin-like growth factor (IGF)-II, insulin-like growth factor binding protein (IGFBP)-1, and 3 secretion and epidermal growth factor (EGF) receptor expression in cultured human luteinized granulosa cells. MATERIALS AND METHODS: Human luteinized granulosa cells were obtained from follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing in vitro fertilization and cultured for 72 hours with TGF-alpha at concentration of 1.0, 10.0, 100.0 ng/ml. The luteinized granulosa cells not treated with TGF-alpha served as control. The secretion of IGF-II, IGFBP-1 and 3 were determined in conditioned media by immunoradiometric assay (IRMA) and reverse transcription-polymerase chain reaction (RT-PCR) was performed for EGF receptor mRNA expression. RESULTS: The cell numbers of 1.0 and 10.0 ng/ml supplement groups were significantly decreased compared to control (p<0.05, p<0.05, respectively), although the cell viabilities were similar in all groups. IGF-II levels were significantly higher in TGF-alpha treatment group at 1.0 and 10.0 ng/ml (p<0.01, p<0.01, respectively), but lower in 100.0 ng/ml (p<0.01). However, the concentrations of IGFBP-1, and 3 per one granulosa cell in each group were no statistically significant differences among the groups. The mRNA concentration of EGF receptor in cultured human luteinized granulosa cells were not significantly different among the groups. CONCLUSION: This study suggests that TGF-alpha regulate intrafollicular bioavailable IGF-II levels, by which TGF-alpha might involved luteinizations. However, TGF-alpha may not directly regulate EGF receptor mRNA expression in cultured human luteinized granulosa cells.

Treatment-Seeking Behaviors among Korean University Women with Premenstrual Symptoms / 대한정신약물학회지

OBJECTIVE: The aim of the present study was to determine the treatment-seeking behaviors of Korean university women with premenstrual symptoms. METHODS: Of 1419 subjects who randomly selected in 4 women's university in Seoul, 771 who experienced at least one premenstrual symptom during past three months were included in this study. Treatment-seeking behaviors for relieving premenstrual symptoms were grouped into five categories [doctor's prescription, self-prescription with over-the-counter drug, use of oriental medicine, use of other conservative-alternative medicine (CAM), nonpharmacological treatment]. We investigated what the preferential treatment was and how many subjects were experienced the medical evaluation by doctor. The attitude and knowledge to premenstrual symptoms were evaluated. RESULTS: Subjects who experienced at least one kind of treatment for relieving premenstrual symptoms were 50.2% of women with premenstrual syndrome (PMS) and 63.6% of premenstrual dysphoric disorder (PMDD). Nonpharmacological treatment such as exercise or rest was the most preferential treatment. Only 2.3% of PMDD was examined and prescribed by doctor. Subjects with doctor's or oriental doctor's prescription had more severe premenstrual symptoms and showed functional impairment than others. Only 7% of university women reported to know well about premenstrual symptoms and their treatment. CONCLUSIONS: This study shows that Korean university women prefer self-diagnosis and self-prescription to the evaluation and prescription by doctor for relieving premenstrual symptoms even though they suffer from PMDD. It indicates that the adequate evaluation and treatment for premenstrual symptoms are not carried out because of the lack of knowledge about them. Therefore, the correct information about symptoms and management of PMS and PMDD should be serviced to general population. Also, systematic evaluation of efficacy and safety of oriental medicine and other CAM for premenstrual symptom is needed.

Mouse embryo culture and implantation by Type I Collagen / 대한산부인과학회잡지

OBJECTIVES: To examine the in vitro interactions of blastocyst attachment using type I collagen. MATERIALS AND METHODS: ICR mice were used and follicular growth was stimulated by pregnant mare serum gonadotropin and human chorionic gonadotropin. On day 4 of pregnancy, the uteri were removed and blastocysts were flushed. Mixtures of 1mL sterile water, 0.5mL DMEM, 2mL type collagen solution and 0.5mL 0.1M NaOH were prepared and transferred to an incubator where the collagen solution polymerized. Blastocysts were transferred to dishes previously coated with type I collagen. CMRL 1066 was used as the basic culture medium. It was supplemented with 1mM glutamine and 1mM sodium pyruvate plus 50 IU/ml penicillin and 50 mg/ml streptomycin. During the first 4 days the culture medium was supplemented with 20% fetal calf serum and thereafter with 20% heat inactivated human cord serum. All blastocysts were initially cultured for 2 days without media change. After 2 days, fresh medium was renewed daily. The stages of embryo growth were examined and recorded everyday under a dissecting microscope and classified according to the standard in vivo criteria set forth by Witschi. RESULTS: By 48h, nearly all blastocysts had attached to the surface of collagen pad. Following adhesion to the collagen pad, the blastocysts maintained their 3-dimensional integrity in contrast to control. The embryos in collagen pad were not flattening and kept polarity and spherical shape during culture. The polar trophoblast invaded the type I collagen downward unlike the horizontal growth in control. In the developmental stage of mouse blastocyst, there were significant differences between control and type I collagen group during day 4 and 5 culture. CONCLUSION: Blastocyst development was better in type I collagen group than control. Therefore, in vitro culture study using type I collagen could provide improved model for the establishment of blastocyst implantation study.

In Vitro Culture of Nontransformed Cell Lines Derived from Rat Endometrial Epithelium and Stroma / 대한불임학회지

Since the blastocyst is broken and spreads out on a flat plastic culture dish (two dimensional culture) during in vitro development, it has been difficult to study the implantation process. It also has been difficult to analyse the interactions between endometrial epithelial and stromal cells because of the lack of a long-term in vitro model which can stimulate in vivo characteristics, as these cells eventually fail to proliferate or cease to express differentiated functions. Recently nontransformed cell lines, CUE-P and CUS-V2, derived from rat endometrial epithelium and stroma were reported. In this study, morphology of CUE-P and CUS-V2 was examined and oxytocin gene expression by CUE-P cells was demonstrated by RT-PCR. The CUE-P cells have a cuboidal morphology and CUS-V2 cells resemble fibroblast and exhibit a spindle-like morphology. In RT-PCR, same size of PCR products of oxytocin gene at hypothalamus, uterus and CUE-P cells were demonstrated. These results showed three dimensional culture system could be made by using the new cell lines.