A Multi-center, Randomized, Controlled and Open Clinical Trial of Heyan Kuntai Capsule () and Hormone Therapy in Perimenopausal Women.

OBJECTIVE: To evaluate the efficacy and safety of Heyan Kuntai Capsule (, HYKT) and hormone therapy (HT) on perimenopausal syndromes (PMSs). METHODS: 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). CONCLUSIONS: 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.

Clinical characteristics of 138 Chinese female patients with idiopathic hypogonadotropic hypogonadism.

OBJECTIVE: To evaluate the clinical features of Chinese women with idiopathic hypogonadotropic hypogonadism (IHH). METHODS: We retrospectively reviewed the clinical characteristics, laboratory and imaging findings, therapeutic management and fertility outcomes of 138 women with IHH. All patients had been treated and followed up at an academic medical centre during 1990-2016. RESULTS: Among the 138 patients, 82 patients (59.4%) were diagnosed with normosmic IHH and 56 patients (40.6%) were diagnosed with Kallmann syndrome (KS). The patients with IHH experienced occasional menses (4.3%), spontaneous thelarche (45.7%) or spontaneous pubarche (50.7%). Women with thelarche had a higher percentage of pubarche (P < 0.001) and higher gonadotropin concentrations (P < 0.01). Olfactory bulb/sulci abnormalities were found during the magnetic resonance imaging (MRI) of all patients with KS. Most patients with IHH had osteopenia and low bone age. Among the 16 women who received gonadotropin-releasing hormone treatment, ovulation induction or assisted reproductive technology, the clinical pregnancy rate was 81.3% and the live birth rate was 68.8%. CONCLUSIONS: The present study revealed that the phenotypic spectrum of women with IHH is broader than typical primary amenorrhoea with no secondary sexual development, including occasional menses, spontaneous thelarche or pubarche. MRI of the olfactory system can facilitate the diagnosis of KS. Pregnancy can be achieved after receiving appropriate treatment.

Comparison of follicle-stimulating hormone, estradiol, ovarian volume, and antral follicle count, based on the Stages of Reproductive Aging Workshop system, among community-based women in China.

OBJECTIVE: This study aims to describe changes in follicle-stimulating hormone (FSH), estradiol (E2), ovarian volume (OV), and antral follicle count (AFC), and to examine their relationships at the same menopause stage, based on the Stages of Reproductive Aging Workshop (STRAW) system, among Chinese women in community settings. METHODS: Prospective longitudinal study design was used to analyze the sex hormone levels, OV, and AFC of 327 community women aged 30 to 65 years. They were followed up at 1 year. RESULTS: Significant differences in FSH, E2, and OV were observed at baseline and on follow-up (all P<0.001). Significant differences in E2 were observed between baseline and follow-up for women in premenopause (-2.743, P=0.006) and late postmenopause (-5.213, P<0.001). There were significant differences in FSH between baseline and follow-up in early menopausal transition (MT) (-2.430, P=0.015) and late MT (-3.737, P<0.001). There were significant differences in OV between baseline and follow-up in late MT (-3.805, P<0.001) and early postmenopause (-4.341, P<0.001). There were significant differences in AFC between baseline and follow-up in premenopause (-2.046, P=0.041). CONCLUSIONS: These results suggest the existence of significant associations between FSH, E2, OV, AFC, and menopause status, supporting the use of the STRAW system among community-based women in China. Further study of the MT is recommended to confirm the appropriateness of the STRAW system for Chinese women.

Pattern of moderate-to-severe symptoms of premenstrual syndrome in a selected hospital in China.

AIM: Premenstrual syndrome (PMS) is a commonly encountered complaint among women. It may affect women's quality of life and reduce their occupational productivity. This study aims to describe the symptoms of moderate-to-severe PMS and to examine the onset, stability, and severity of PMS among Chinese women. METHODS: A descriptive study included 142 women with self-reported PMS, aged 18-45 years, who were recruited by the Outpatient Department of Gynecological Endocrinology, Peking Union Medical College Hospital. Premenstrual symptoms were retrospectively assessed by using screening questionnaires modified with the DSM-IV. In total, 126 eligible subjects were asked to record their daily symptoms during two consecutive menstrual cycles by using a premenstrual syndrome diary (PMSD). RESULTS: Of 126 eligible subjects, 67 filled in the PMSD for two cycles. The median of total scores of PMSD peaked on the day before menses and dropped after the beginning of the menses. Mood swings were the most common moderate-to-severe symptom prospectively reported by the subjects. The symptoms of PMS were relatively consistent across the two cycles. CONCLUSIONS: Women with moderate-to-severe PMS were vulnerable to psychological symptoms. Further studies are needed to understand the correlations between hormonal changes and the experience of symptoms related to the menstrual cycle.

[Evaluation the efficacy and safety of estradiol and drospirenone tablets in the treatment of menopausal symptoms among postmenopausal Chinese healthy women:a randomized, multi-center, double-blind, placebo-controlled clinical study].

OBJECTIVE: To study the efficacy and safety of estradiol and drospirenone tablets (Angeliq) in treatment of menopausal symptoms among postmenopausal Chinese healthy women. METHODS: Total 244 postmenopausal Chinese healthy women who had moderate to severe hot flushes were randomly assigned into estradiol and drospirenone (observation group, n = 183) or placebo group (n = 61) by the ratio of 3:1 for 16 weeks in this randomized multi-center double-blind placebo-controlled study. During the trial, the follow-up visits were conducted at week 4, 8, 12, 16 of treatment and 2 weeks after treatment respectively. Height, weight, vital signs, hot flushes, other relevant menopausal symptoms and vaginal bleeding were observed in each follow-up visit, while the clinical global impression scale was assessed at 16 weeks as well. RESULTS: It showed that hot flushes were reduced significantly more in observation group than that in placebo group (P < 0.01), although both treatments were effective. The absolute values of mean severity index of total hot flushes decreased by -0.6 ± 0.5 in observation group and -0.4 ± 0.4 in placebo group from baseline respectively, which reached significant difference (P < 0.05). However, the absolute values of mean severity index of moderate to severe hot flushes decreased by -0.6 ± 0.8 in observation group and -0.3 ± 0.6 in placebo group from baseline respectively, which had no significant difference (P > 0.05). After 16 weeks treatment, it also showed that estradiol and drospirenone had significant better efficacy than placebo on moderate to severe sweating, vaginal dryness and clinical global impression scale (P < 0.01). During the trial, blood pressure in observation group was stable. The rate of vaginal bleeding in observation group was higher than that in the placebo group, especially during the week 4 to week 8 when 48.9% (87/178) in observation group and 10.7% (6/56) in placebo group of patients bled. Although the cumulative amenorrhea rate of observation group was lower than that of placebo group in each cycle (28 days), it increased gradually along with duration of the treatment. The commonest adverse event in observation group was breast tenderness which accounted for 12.0% (22/183). The level of serum potassium was in the normal range in observation group mostly.Meanwhile, the other adverse events rate was low. Serious adverse events reported in this trial were assessed as not study drug related or as unlikely study drug related. CONCLUSION: Estradiol and drospirenone tablets which could effectively alleviate menopausal symptoms in postmenopausal Chinese healthy women is a novel hormone replacement therapy regimen with high safety and efficacy.

Serum lipid profile changes during the menopausal transition in Chinese women: a community-based cohort study.

OBJECTIVE: The aim of this study was to examine the changes in serum lipid profile related to the stages of the menopausal transition as defined by prospective menstrual pattern. METHODS: A total of 593 healthy women aged 35 to 64 years were followed annually for up to 3 years (average, 1.6 y), and 1,549 observations were provided. Blood samples were collected from all participants. Serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, TC/HDL-C, estradiol, and follicle-stimulating hormone were assessed. Menopause status was defined by the menstrual change criteria of the Stages of Reproductive Aging Workshop. RESULTS: After adjusting for age, body mass index, physical activity, and antihypertensive medication use, TC, TG, and TC/HDL-C increased to peak in the late perimenopause (increased by 7.1 mg/dL in TC, 12.3 mg/dL in TG, and 0.19 in TC/HDL-C; all P < 0.05) compared with the premenopause status group. We did not find any statistically significant difference between the premenopause and postmenopause status groups in all lipid profile variables. Among postmenopausal women, only TG decreased by 8.2 mg/dL in the late postmenopause (P < 0.01). In contrast, there is no significant change in HDL-C among the different menopause status groups. CONCLUSIONS: Our data suggest that the menopausal transition instead of menopause per se is associated with serum lipid profile in community-based women in China. Late perimenopause status is significantly associated with accelerated increase in TC, TG, and TC/HDL-C. HDL-C seemed to have no relationship with menopause status.

[Safety of promestriene capsule used in postmenopausal atrophic vaginitis].

OBJECTIVE: To investigate the safety and efficacy of promestriene capsule used in the treatment of postmenopausal atrophic vaginitis. METHODS: Fifty-three women at age of 45 - 75 years (more than one year history of menopause) diagnosed with postmenopausal atrophic vaginitis were enrolled in self-control study. They all had typicalsymptoms of postmenopausal vaginitis. Promestriene was given by continuous therapy for 20 days, then maintenance therapy for for 8 weeks (1 pill two times per week used). The level of follicle stimulation hormone (FSH) and estradiol (E(2)) in serum was and thickness of endometrium were detected before and after treatment. The routine biochemical test was used as index to monitoring the safety. The vaginal mature index (VMI), the atrophic vaginitis evaluating score and vaginal healthy evaluating score were evaluated for therapeutic effect. In the mean time, adverse effect was recorded. RESULTS: (1) SAFETY: during promestriene treatment, no case with adverse effect was observed. Before treatment, the mean level of FSH and E(2) was (71 +/- 3) U/L and (41 +/- 18) pmol/L, the mean thickness of endometrium was (2.4 +/- 0.9) mm. After treatment, the mean level of FSH and E(2) was (67 +/- 22) U/L and (43 +/- 37) pmol/L, the mean thickness of endometrium was (2.5 +/- 1.3) mm. No significant difference was observed (P > 0.05). (2) Therapeutic effect: VMI were 42 +/- 15 before and 54 +/- 8 after treatment. The atrophic vaginitis evaluating score were 3.4 +/- 1.7 before and 1.5 +/- 1.4 after treatment. Vaginal healthy evaluating score were 7.8 +/- 2.4 before and 12.0 +/- 2.4 after treatment. They all showed significant difference (P < 0.01). (3) Adverse effect: six cases with vaginal bleeding, 3 cases with breast nodules and 1 case with cervical polyp was observed, however, it was uncertain whether those events were associated with promestriene use. CONCLUSION: The premestriene capsule was safe and effective in the treatment of postmenopausal atrophic vaginitis.

Effect of estrogen on gene expression of fatty acid synthase in periosteum.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Estrogen modulates FAS gene expression in in vitro human perisoteum as well as in in vivo rat periosteum.

[Cost-effectiveness analysis of two therapeutic methods for prolactinoma].

OBJECTIVE: To evaluate the therapeutic responses to transsphenoidal surgery and medical therapy in terms of normalization of prolactin (PRL), mortality, morbidity and the cost-effectiveness of PRL normalization in order to establish an individualized therapeutic protocol for the patients with prolactinoma. METHODS: A retrospective study was undertaken of a consecutive series of patients with prolactinoma who were followed for at least 1 year after transsphenoidal surgery or medical treatment. The clinical characteristics and the long-term outcomes (normalization of PRL, morbidity or mortality) were assessed. Utilizing the principle of medical economics and data from the two types of treatment, we worked out a Markov chain and calculated the lowest cost of two kinds of therapeutic protocols. RESULTS: (1) The success rate of normalizing serum PRL through surgical treatment in microadenoma was 85% (22/26), and that of medical treatment was 95% (19/20). There was no statistical difference between the two therapies (P > 0.05). The success rate of normalizing serum PRL through surgical treatment in macroadenoma was 45% (19/42), and that of medical treatment was 5/5. There was a statistical difference between the two therapies (P < 0.05). (2) According to the Markov model, it would cost a microprolactinoma patient 25,129.25 yuan to normalize serum PRL by surgical treatment. This is comparable to the cost of medical treatment which would be 24,943.99 yuan. Whereas for a macroprolactinoma patient surgery would cost 35,208.20 yuan and medical treatment would cost 25,344.38 yuan. CONCLUSIONS: Medical therapy is superior to surgical treatment in regard to complication rate and cost-effectiveness for macro- and extra big prolactinomas. Transsphenoidal surgery remains an option for patients with microadenomas. Markov model is an effective way to predict the treatment cost for patients with hyperprolactinoma at different ages and with different causes.

A potential mechanism of breakthrough bleeding associated with progestin: involvement in alteration of endometrial endothelial cells.

OBJECTIVE: To explore the potential mechanism of breakthrough bleeding associated with progestin with in vitro methods. METHODS: 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. RESULTS: 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. CONCLUSION: 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

Genistein inhibits proliferation of human endometrial endothelial cell in vitro.

OBJECTIVE: To explore the effect of genistein on proliferation of human endometrial endothelial cells (HEECs) and glandular epithelium. METHODS: 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. RESULTS: 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. CONCLUSION: Genistein at the concentration of 200 micromol/L can sufficiently inhibit the proliferation of HEECs and endometrial glandular epithelium simultaneously in vitro.

[Effect of age on body composition in healthy Beijing women].

OBJECTIVE: To observe the effect of age and menstrual status on body composition in healthy Beijing women. METHODS: We measured body composition with dual-energy X-ray (GE Lunar Prodigy) in 316 healthy Beijing females aged 20 to 74 years (5-7 cases per age). Parameters provided by the software were as following: total body bone mineral content, lean mass, fat mass and fat percentage (%fat). Local regions measured included arm, leg, trunk, android region and gynoid region. Body mass index (BMI), fat mass index (FMI), free fat mass index (FFMI) and A/G were calculated. Volunteers were assigned to 6 groups according age by every ten years a group. RESULTS: BMC peaked during the 4th decade, LM peaked during the 5th decade, with a decline of 18.1% and 5.2% respectively at age 74 years. Total body fat mass and %fat showed a general increase with aging throughout the studied age range. Total body fat mass increased from 16+/-5 kg at age 20-29 years to 24+/-6 kg at age 70-74 years, while %fat increased from 31.3% to 39.5%. All local region %fat increased with aging at different extents. Android region %fat showed the largest raise extent (32.2%). BMI increased gradually from 21.1 kg/m2 at age 20-29 years to 26.1 kg/m2 at age 70-74 years. FMI changed more obviously than FFMI. A/G increased from 0.85 at age 20-29 years to 1.02 at age 70-74 years. Different menstrual status in women of 40-59 years had obvious effect on A/G and BMC (P<0.05), while it had no significant effect on BMI, body weight and waist circumference (P>0.05). CONCLUSIONS: Aging and menstrual status have evident effect on body composition distribution in healthy Beijing women.

Incidence of osteonecrosis of the jaw in women with postmenopausal osteoporosis in the health outcomes and reduced incidence with zoledronic acid once yearly pivotal fracture trial.

BACKGROUND: The authors determined incidence of osteonecrosis of the jaw (ONJ) in a large, prospective three-year clinical trial of zoledronic acid in women with postmenopausal osteoporosis (PMO). METHODS: A total of 7,714 women with PMO received intravenous zoledronic acid 5 mg or a placebo. No spontaneous reports of ONJ were received. An independent, blinded adjudication committee searched the trial's adverse event database by using 60 terms. On an ongoing basis, the committee reviewed the identified events, and it defined ONJ as exposed bone in the maxillofacial area with delayed healing for more than six weeks despite appropriate care. RESULTS: One participant who received a placebo and one participant who received zoledronic acid experienced delayed healing associated with infection. Both conditions resolved after antibiotic therapy, débridement or both. CONCLUSION: The occurrence of ONJ is rare in a PMO population, and delayed healing of lesions can occur with and without bisphosphonate use over three years. CLINICAL IMPLICATIONS: The low incidence of ONJ must be assessed in the context of the clinical benefit of zoledronic acid therapy in reducing hip, vertebral and nonvertebral fractures in this at-risk population. There is no evidence to suggest that healthy patients with osteoporosis who are receiving bisphosphonates require any special treatment beyond routine dental care or to support altering standard treatment practices.

Impact of menopause on quality of life in community-based women in China.

OBJECTIVE: To assess the impact of menopause, age, and other factors on quality of life (QOL). DESIGN: Generally healthy women aged 35 to 64 years were recruited from a general community in Beijing, People's Republic of China. An instrument including the Chinese version of the Menopause-Specific Quality of Life Questionnaire was used to obtain data. RESULTS: A gradual decline of QOL was seen from pre- to peri- and postmenopausal women in the same age group. Statistically impaired QOL was associated with the peri- and postmenopausal women in vasomotor and physical domains but only with the postmenopausal women in psychosocial and sexual domains. Early postmenopausal women presented the worse QOL in vasomotor, psychosocial and physical domains. The gradually declining sexual QOL was related to the advance of menopause. Age had a negative impact on QOL in vasomotor and sexual domains. Women who assessed their own health as common (fair) or weak (poor) reported worse QOL than those who decribed themselves as healthy. Women with a higher body mass index reported more vasomotor symptoms. CONCLUSIONS: Menopause might have a negative impact on QOL independent of age in community-based women in China. There seemed to be a potential model of the relationship of menopause status to change in QOL, but this needs supporting evidence from longitudinal studies. The association of QOL with age and other factors also should be considered.

Menopause-specific quality of life satisfaction in community-dwelling menopausal women in China.

The present study aimed to evaluate the satisfaction with quality of life of menopausal women living in an urban community of Beijing, People's Republic of China, using the Chinese version of the menopause-specific quality of life questionnaire (MENQOL). Menopause-related complaints were assessed for 353 women aged 40-60 years during their menopausal transition (MT) or postmenopause (PM) using MENQOL. The Kruskal-Wallis non-parametric test and Pearson correlation were used for statistical analysis. The mean age of the subjects was 51.20 +/- 4.62 years. The most frequent symptom was 'experiencing poor memory' (84.1%) and the least frequent was 'dissatisfaction with personal life' (26.9%). Mean scores of vasomotor and sexual symptoms in PM women were higher than in MT women (2.60 +/- 1.74 and 3.39 +/- 2.35 vs. 1.96 +/- 1.46 and 2.10 +/- 1.48, respectively; p = 0.0001). The prevalence of menopause-related symptoms varied between self-assessed health status groups (chi(2) = 29.12, p = 0.0001). In conclusion, MENQOL is a good self-administered tool in the assessment of climacteric complaints, with convenient application. The most frequent climacteric symptom of Chinese women living in an urban community was 'experiencing poor memory'. PM women seemed to suffer from more symptoms, especially in vasomotor and sexual domains, than did MT women. Symptom reports might be associated with self-assessed health status.

[Profiles of irregular bleeding induced by low-dose hormone therapy and Chinese formulated herbs products].

OBJECTIVE: 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. METHODS: 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. CONCLUSION: 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.

[Effect of combined continued hormone replacement therapy on knee osteoarthritis symptom of postmenopausal women].

OBJECTIVE: To study the effect of combined continued estrogen and progestin replacement therapy on knee osteoarthritis (OA) symptoms of postmenopausal women. METHODS: 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. RESULTS: 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). CONCLUSION: Combined estrogen and progestin replacement therapy can relieve the knee OA symptoms of postmenopausal women.

[Germline mutations in the BRCA1 and BRCA2 genes from breast cancer families in China Han people].

OBJECTIVE: To detect BRCA1 and BRCA2 gene germline mutation in the Chinese breast cancer families. METHODS: Samples of peripheral blood were collected to prepare genomic DNA by conventional techniques from 15 inherited breast cancer patients from 14 breast cancer families, 76 sporadic breast cancer patients, and 100 healthy controls based on informed consent. Exons 4, 8, 11 and 18 - 20 of BRCA1, and exons 1 - 14, 17 - 24 and 27 of BRCA2, were analyzed using DNA direct sequencing. RESULTS: Six single nucleotide polymorphisms (SNPs) were found on the exon 11 of BRCA1, 2 being silent changes without change of amino acid coding, and 4 with change of amino acid coding among which 2 were polymorphic amino acid alterations and 2 were pathogenic SNPs, i.e. mutational sites. One novel BRCA1 mutation, C1196T (Pro 359 Leu), was identified in a family breast cancer patients, who was diagnosed at the age of 37. Another BRCA1 mutation, Trp 372 stop was found in a breast cancer patient who was diagnosed at the age 29. Eight SNPs were found on the exon3, 10 and 11 of BRCA2, among which 5 were silent changes and 3 were polymorphic amino acid alterations. A1093C (Asn289His) in exon 10 and A 3199G (Asn991Asp) in exon 11 being found simultaneously in the patients of 2 families but not appearing in pool DNA sample, and Asn 371 His appearing as A/C heterozygote in pool DNA sample. CONCLUSION: Two pathogenic SNPs have been found in BRCA1 and may be related to early-onset breast cancer. One of them may be a novel mutation characterized of familial breast cancer in China.

[Monitoring the breast changes of Chinese postmenopausal women under long-term hormone replacement therapy by mammary ultrasonography].

OBJECTIVE: To investigate the effects of long-term hormone replacement therapy (HRT) on the breasts of postmenopausal women using mammary ultrasonography. METHODS: 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. RESULTS: (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). CONCLUSIONS: 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.