A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule () and Hormone Therapy in Perimenopausal Women / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs).</p><p><b>METHODS</b>From 2005 to 2008, 390 women with PMSs were recruited from 4 clinic centers. The inclusion criteria included ages 40 to 60 years, estradiol (E2) below 30 ng/L, and follicle stimulating hormone (FSH) above 40 IU/L, etc. The patients were randomly assigned to HYKT group or HT group by random number table method, administrated HYKT or conjugated estrogen with/without medroxyprogesterone acetate tablets for 12 months. During treatment, the patients were interviewed quarterly, Kupperman Menopausal Index (KMI) scores, hot flush scores, insomnia scores, Menopause-Specific Quality of Life (MENQOL) scores and adverse effects were used for evaluating drug efficacy and safety respectively. The last interview was made at the end of 12-month treatment RESULTS: After treatment, KMI scores of HYKT group and HT group were both significantly decreased compared with baseline (P <0.01) and there was no significant difference between groups (P >0.05), except that KMI of HYKT group was higher after 3-month treatment (P <0.05). After treatment, hot flush and insomnia scores were both improved significantly in two groups (P <0.01); and HT had a better performance than HYKT in improving hot flush (P <0.05). MENQOL were significantly improved in both groups after treatment (P <0.01); but there was no significant difference between two groups (P >0.05). The incidence of adverse event in the HYKT group was much lower than that in the HT group (P <0.01).</p><p><b>CONCLUSIONS</b>HYKT could effectively relieve PMSs and improve patients quality of life without severe adverse reactions. Although HYKT exerted curative effects more slowly than hormone, it possessed better safety profile than hormone.</p>

Effect of estrogen on gene expression of fatty acid synthase in periosteum / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Estrogen deficiency contributes to postmenopausal osteoporosis. Periosteum might be a potential target of estrogen, but the underlying mechanism at gene level is far from being elucidated. The objective of this study was to investigate the correlation between estrogen and fatty acid synthase (FAS) expression in periosteum.</p><p><b>METHODS</b>Human periosteum cells were cultured in vitro. Expressed genes in the substrated cDNA library were verified using semi-quantitative PCR and real-time PCR. The expression of FAS in periosteum of ovarectomized (OVX) SD rats was investigated.</p><p><b>RESULTS</b>FAS gene was most significantly expressed in the subtracted cDNA library of periosteal cells screened by semi-quantitative PCR. Low FAS expression was verified by real-time PCR in the estrogen exposed human periosteum rather than in the control. The estradiol levels were (20.81 +/- 12.62) pg/ml, (19.64 +/- 4.35) pg/ml and (13.47 +/- 1.84) pg/ml in the sham group, the control, and the OVX group, respectively. The estradiol levels in the OVX group was significantly lower (P = 0.0386). The FAS gene expression in periosteum in the OVX group, sham group, and control group was 3.09 +/- 1.97, 1.33 +/- 0.47 and 1.51 +/- 1.32, respectively. The gene expression in the OVX group was significantly higher (P = 0.0372).</p><p><b>CONCLUSION</b>Estrogen modulates FAS gene expression in in vitro human perisoteum as well as in in vivo rat periosteum.</p>

A potential mechanism of breakthrough bleeding associated with progestin: involvement in alteration of endometrial endothelial cells / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods.</p><p><b>METHODS</b>The isolation and culture of human endometrial endothelial cells (HEECs) was performed with the method established in our laboratory. The content and activity of urokinase-type plasminogen activator (uPA) and the content of plasminogen activator inhibitor-1 (PAI-1) in cell supernatants after incubated with different concentrations of progesterone (0-5 micromol/L) and 17beta-estradiol (0, 0.1, or 1 nmol/L) were measured by method of ELISA. Apoptosis rate of HEECs was measured by flow cytometry. Viable cell count was measured by MTT.</p><p><b>RESULTS</b>The increased level of progesterone (0.5-5 micromol/L) combined with 17beta-estradiol elevated content and activity of uPA while the production of PAI-1 remained unchanged. The apoptosis of HEECs was inhibited along with the increment of total viable cell counts at higher concentrations of progesterone with 17beta-estradiol.</p><p><b>CONCLUSION</b>The inhibition of apoptosis and increased content and activity of uPA may contribute to the occurrence of irregular bleeding associated with progestin use to some extent</p>

Genistein inhibits proliferation of human endometrial endothelial cell in vitro / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To explore the effect of genistein on proliferation of human endometrial endothelial cells (HEECs) and glandular epithelium.</p><p><b>METHODS</b>In vitro HEECs and human endometrial cancer-1B cell (HEC-1B) were cultured with 0, 1, 10, 50, 100, and 200 micromol/L of genistein alone or indicated concentrations of genistein combined with 0.2 or 1 nmol/L 17beta-estradiol (17beta-E2). Cell proliferation was determined by [3H]-thymidine incorporation and cell cycle was measured by flow cytometry.</p><p><b>RESULTS</b>After 96 hours of treatment, genistein inhibited the proliferation of HEECs in a dose-dependent manner. The stimulation index reduced from 100% (without genistein treatment) to about 1% (200 micromol/L genistein). HEECs were arrested at G1/0 and G2/M phase when treated with genistein for 96 hours. When the concentration of genistein was 200 micromol/L, the percentages of HEECs at G1/0, G2/M, and S phase were 96.0%, 2.1%, and 1.9%, respectively. However, when HEECs were treated without genistein, the percentages of HEECs at G1/0, G2/M, and S phase were 76.7%, 8.5%, and 14.7%, respectively. 17beta-E2 could not influence the effects of genistein on the proliferation of HEECs. Meanwhile, genistein could suppress the proliferation of HEC-1B. If the stimulation index of HEC-1B was defined as 100% when HEC-1B was treated with different doses of 17beta-E2 (without genistein), it was 67%, 19%, as well as 32% when cell was supplemented with 200 micromol/L genistein combined with 0, 0.2, or 1 nmol/L 17beta-E2, respectively.</p><p><b>CONCLUSION</b>Genistein at the concentration of 200 micromol/L can sufficiently inhibit the proliferation of HEECs and endometrial glandular epithelium simultaneously in vitro.</p>

Profiles of irregular bleeding induced by low-dose hormone therapy and Chinese formulated herbs products / 中国医学科学院学报

<p><b>OBJECTIVE</b>To compare profiles and related factors of irregular bleeding induced by different types of low-dose hormone therapy (HT) and a Chinese formulated herbs products.</p><p><b>METHODS</b>Applied with open-labeled, randomized, and clinical trial design, 136 postmenopausal women were assigned into four groups: group A: estradiol valerate (E2 V) 1 mg/d + medroxyprogesterone acetate (MPA) 2 mg/d; group B: conjugated equine estrogen 0.45 mg/d + MPA 2 mg/d; group C: tibolone 1.25 mg/d; group D: a Chinese formulated herbs product (Kuntai) 4# tid. Each subject took element calcium 400 mg/d and vitamin D 200 IU/d concomitantly. Modified Kupperman scores were assessed on baseline and every 3 months thereafter and irregular bleeding was recorded on menopausal diary every day. The duration of this study was 1 year. Results The efficacies were similar in three HT-managed groups, but was better than in group D, although the latter was also effective in alleviating menopausal symptoms. Hazard ratio (HR) of irregular bleeding was 1.00 in group C, 2.43 in group A (95% CI: 1.08-5.46), 3.12 in group B (95% CI: 1.42-6.88), and 0.73 in group D (95% CI: 0.26-2.04). Most cases initially experienced bleeding in the first 3 months but such initiation was a bit later in group C. Endometrium, as detected by B-mode ultrasound, increased approximately 1 mm in HT groups, while it was a bit thicker in group C. Long periods in reproductive age and short time since menopause were high risk factors for irregular bleeding.</p><p><b>CONCLUSION</b>Profiles of irregular bleeding in 3 commonly used types of low-dose HT are different and some factors such as long period in reproductive age and short time since menopause may contribute to bleeding initiation.</p>

Monitoring the breast changes of Chinese postmenopausal women under long-term hormone replacement therapy by mammary ultrasonography / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the effects of long-term hormone replacement therapy (HRT) on the breasts of postmenopausal women using mammary ultrasonography.</p><p><b>METHODS</b>An open randomized clinical study was designed. The percutaneous estradiol gel was used in a cyclic regimen combined with micronized progesterone (MP) or medroxyprogesterone acetate (MPA). Sixty healthy women (natural menopause for 1 to 5 years) were recruited and divided into four groups according to the dosage of estrogen and two kinds of progestin. All were given for 25 days per month. Mammary ultrasonography was used to observe breast glandular section thickness, breast duct width, the morphology of lobular unit and the blood flow of color Doppler imaging at baseline and every year from the second to seventh year of HRT. The serum estradiol was also measured from the 15th to 25th day of the cycle. Breast pain was recorded by the subjects.</p><p><b>RESULTS</b>(1) The breast glandular section thickness after HRT was larger than that of before HRT. The breast glandular section thickness became larger gradually over time while the breast duct width became smaller over time. The breast duct width of the fifth year of HRT was significantly different from that of the sixth year (P < 0.05). (2) Twenty-two persons had new breast structure changes after HRT, and the accumulated incidence was 41.5%. New solid lesions formation occurred in five subjects (8.3%) and new cyst formation occurred in one subject (1.7%). After the second year of HRT, the serum estradiol level of the subjects with breast structure changes was higher than that of without breast structure changes and in the sixth year of HRT, and the difference was significant (P < 0.05). After the second year of HRT, the breast glandular section thickness of the subjects with breast structure changes was larger than that of without breast structure changes and in the fifth and sixth year of HRT, the difference was significant (P < 0.05). (3) After HRT, the serum estradiol level of subjects with mastalgia was higher than that of without mastalgia and in the second and sixth follow-up year, the difference was significant (P < 0.05).</p><p><b>CONCLUSIONS</b>There is an increasing trend of the percentage of glandular tissues of the breast after HRT. There is an increasing trend of the serum estradiol level and the breast glandular section thickness among the subjects with the breast structure changes; there is an increasing trend of the serum estradiol level among the subjects with mastalgia. Mammary ultrasonography can be used to monitor breast structure changes and breast lesions during HRT.</p>

Effect of combined continued hormone replacement therapy on knee osteoarthritis symptom of postmenopausal women / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the effect of combined continued estrogen and progestin replacement therapy on knee osteoarthritis (OA) symptoms of postmenopausal women.</p><p><b>METHODS</b>Sixty-four postmenopausal women with radiological knee OA and symptoms aged 45-75 were divided into treatment group and control group. They were given estradiol velerate (E2V) 1.0 mg/d and medroxyprogestetone acetate (MPA) 2 mg/d (treatment group) or placebo (control group) for 6 months. Calcium 400 mg/d were given to all cases. Then 0-100 mm visual analon scale (VAS) was used to evaluate the severity of knee pain at baseline and after 1, 3, 6 month of treatment.</p><p><b>RESULTS</b>Significant differences on pain at night and tenderness around knee were seen in the treatment group compared with the control group after 1 months of treatment (P = 0.036 and 0.035, respectively). The improvement of pain at night, during walk and morning stiffness between the two groups showed significant difference after 6 months (P = 0.026, 0.027, and 0.011, respectively).</p><p><b>CONCLUSION</b>Combined estrogen and progestin replacement therapy can relieve the knee OA symptoms of postmenopausal women.</p>