Global consensus statement on menopausal hormone therapy.

The following Consensus Statement is endorsed by The American Society for Reproductive Medicine, The Asia Pacific Menopause Federation, The Endocrine Society, The European Menopause and Andropause Society, The International Menopause Society, The International Osteoporosis Foundation and The North American Menopause Society.

The Efficacy of Herbal Supplement Danggui Buxue Tang for Relieving Menopausal Symptoms.

OBJECTIVES: This study aimed to further explore the efficacy and safety of Danggui Buxue Tang (DBT), a simple herbal formula, for improving the quality of life of women suffering from menopausal symptoms. METHODS: A third clinical trial to determine the clinical efficacy of high-dose DBT for a period of 12 weeks was carried out. The standard Menopause-Specific Quality of Life (MENQOL) assessment chart was used for the evaluation. Safety was defined as an absence of direct estrogenic effects, serum inflammatory cytokines. Notably, interleukin IL-6, IL-8 and tumor necrosis factor TNF-α, known to be directly related to estrogenic reactions in menopause studies, were monitored. RESULTS: The third clinical trial indicated an overall improvement in the four domains of MENQOL, offering further proof of the efficacy of DBT demonstrated in the two previous trials. The serial checks of the three cytokines related to estrogen activities did not show either upward or downward trends. The haphazard behavior reactions of the three cytokines offered indirect indications that DBT improved the MENQOL independently from estrogen activities. CONCLUSIONS: The three clinical trials using DBT to relieve menopausal syndrome have offered solid evidence for its efficacy. The uncertainty regarding whether the "phytoestrogen" contained in DBT had bioactivities similar to estrogen was alleviated through the confirmation that no strict estrogenic bioactivities were observed. The issue of safety was further clarified via laboratory platform studies on DBT, which not only showed the lack of similarity with estrogen actions but also confirmed the value of combining the two herbs in the classic formula.

Menopause management: a cardiovascular risk-based approach.

Hormone replacement therapy (HRT) remains the gold standard for the management of menopausal symptoms; however, HRT use has declined due to concerns over possible adverse side-effects. Approaches to menopause management are continually being revised and these extend beyond the control of recognized menopausal symptoms to encompass wider aspects of menopausal women's health. Hypertension and associated cardiovascular risk are particularly important unmet needs in postmenopausal women, especially in the Asia-Pacific region which has a rapidly aging population and bears around half of the global burden of cardiovascular disease, two-thirds of which has been attributed to elevated blood pressure. As first point of contact for women with menopausal symptoms, gynecologists play a gatekeeper role in assessing women's health, providing appropriate lifestyle counseling, and, where appropriate, implementing treatment or referral to relevant specialists. This paper, with contributions by gynecologists and cardiologists from Asia Pacific and beyond, summarizes available evidence and provides a treatment algorithm that employs a flexible blood pressure classification strategy to assist physicians in their decision-making for the individualized management of menopausal symptoms in women with low, moderate and high cardiovascular risk, and also for women with diabetes. Individualized HRT according to cardiovascular risk may yield improvements in cardiovascular health, as well as managing menopausal symptoms.

Cardiovascular risks and metabolic syndrome in Hong Kong Chinese women with polycystic ovary syndrome.

BACKGROUND: Women with polycystic ovary syndrome (PCOS) frequently exhibit central obesity, glucose intolerance, atherogenic dyslipidaemia and hypertension which are characteristic features of the metabolic syndrome (MetS). METHODS: A total of 295 premenopausal Chinese women with PCOS diagnosed by the Rotterdam criteria (mean age: 30.2 +/- 6.4 years) and 98 control subjects without PCOS were evaluated for prevalence of MetS and cardiovascular risk factors, including dyslipidaemia and dysglycaemia. RESULTS: Using the 2005 modified Adult Treatment Panel III criteria, MetS (presence of three or more risk factors) was found in 24.9% of PCOS women compared to 3.1% of controls. The prevalence of MetS in PCOS women increased from 16.7% at under 30 years of age to 53.3% at over 40 years. MetS was also more prevalent in overweight and obese (41.3%) than normal-weight PCOS women (0.9%). However, multivariate regression analysis showed that women with PCOS had a 5-fold increase in risk of MetS (odds ratio 4.90; 95% confidence interval: 1.35-17.84) compared with women without PCOS even after controlling for age and BMI, suggesting PCOS alone is an independent risk factor for MetS. CONCLUSIONS: There is high prevalence of MetS in Hong Kong Chinese women with PCOS despite their relatively young age. Recognition of these cardiometabolic risk factors requires a high level of awareness in conjunction with early and regular screening.

A randomized, double-blind, placebo-controlled study of the effect of a Chinese herbal medicine preparation (Dang Gui Buxue Tang) on menopausal symptoms in Hong Kong Chinese women.

OBJECTIVE: Many complementary or alternative medicines are being used for the treatment of menopausal symptoms but most have not been properly tested for efficacy or for safety. This study examined the effect of a Chinese herbal preparation (Dang Gui Buxue Tang) on menopausal symptoms in Hong Kong Chinese women. METHODS: A 6-month randomized, double-blind, placebo-controlled study of the effect of Dang Gui Buxue Tang (a 1 : 5 combination of Dang Gui (Angelicae sinensis) and Huang Qi (Astragalus membranaceus)) on acute menopausal symptoms. A total of 103 symptomatic women were enrolled. Three failed to meet inclusion criteria, leaving 50 subjects for inclusion in each group. RESULTS: Overall, mild hot flushes were reported more frequently than either moderate or severe flushes. In analysis by severity of flushes, there was a significant reduction in the number of mild hot flushes per month in the treatment group but not in the placebo group (from 18.9 +/- 23.5 at baseline to 8.6 +/- 17.1 at 6 months in the treatment group (p < 0.01) and from 26.0 +/- 43.5 to 12.4 +/- 17.6 in the placebo group (p = 0.062)). For moderate flushes, there was a significant reduction in the placebo group compared with the treatment group (from 18.9 +/- 28.7 at baseline to 11.1 +/- 29.9 at 6 months in the placebo group (p < 0.05) and from 10.5 +/- 22.3 to 6.0 +/- 16.0 in the treatment group (p = 0.107)). There was no significant change in either treatment or placebo groups in the reporting of severe hot flushes. Episodes of night sweats decreased significantly in the placebo but not in the treatment group (from 6.8 +/- 10.0 at baseline to 1.9 +/- 5.7 at 6 months in the placebo group (p < 0.05) and from 5.4 +/- 8.9 to 3.2 +/- 8.5 in the treatment group (p = 0.471)). In the vasomotor domain of the Menopause Specific Quality of Life, there was a significant reduction in scoring in the placebo group (from 2.8 +/- 1.6 to 1.7 +/- 1.3, p < 0.01) but not in the treatment group (from 2.8 +/- 2.1 to 2.3 +/- 1.6, p = 0.247). CONCLUSIONS: This study found overall no significant difference between Dang Gui Buxue Tang and placebo in the treatment of vasomotor symptoms in Hong Kong Chinese women. The frequency of mild, moderate and severe hot flushes decreased in both treatment and placebo groups, but Dang Gui Buxue Tang was statistically superior to placebo only in the treatment of mild hot flushes. There were no serious adverse events attributable to treatment during the study period.

Menopausal symptoms in mid-life women in southern China.

OBJECTIVES: To explore the prevalence of menopausal symptoms in Chinese women aged 40-65 years living in Guangdong province in southern China, and to investigate their care-seeking behavior. DESIGN: A cross-sectional population-based study performed in Guangdong province, PR China. METHODS: A total of 9939 women were selected by multistage cluster sampling. From November 2003 to July 2004, women were interviewed in person with a prepared questionnaire about symptoms experienced in the 2 months preceding the survey. The main outcome measurements were self-reported menopausal symptoms and related factors. RESULTS: The mean age of natural menopause was 48.9 years. The prevalence and severity of menopausal symptoms were low. The three most prevalent symptoms were insomnia, joint and muscle pain, and dizziness (in 37.2%, 35.7%, and 31.5% of the sample, respectively). Hot flushes were experienced by 17.5% of women. The factors associated with the frequency of menopausal symptoms included profession, education, type of menopause and the presence of physical or emotional problems. Ever and current hormone replacement therapy usage was reported in 0.8% and 1.3% of women, respectively. Of the total study population, 28.9% had sought health care because of menopausal symptoms. CONCLUSIONS: The prevalence of menopausal symptoms in southern Chinese women is low, and this is accompanied by low usage of hormone replacement therapy.

Polycystic ovarian syndrome in Hong Kong Chinese women: patient characteristics and diagnostic criteria.

OBJECTIVES: To identify the characteristics of Hong Kong Chinese women with polycystic ovarian syndrome and to compare different diagnostic criteria. DESIGN: Retrospective study. SETTING: Gynae-endocrinology Clinics in the Prince of Wales Hospital, Hong Kong. PATIENTS: Ninety Hong Kong Chinese women with polycystic ovarian syndrome who were diagnosed according to the hospital's criteria. MAIN OUTCOME MEASURES: Prevalence of typical features of polycystic ovarian syndrome, including anovulation and hyperandrogenism (with other endocrine causes excluded), polycystic ovarian features on ultrasonography, luteinising hormone predominance, obesity, and insulin resistance. RESULTS: Almost all (98.9%) patients with polycystic ovarian syndrome presented with anovulation, only 48.9% of them had clinical or biochemical evidence of hyperandrogenism. Typical ultrasound appearances of polycystic ovaries were observed in 86.7% of patients. Luteinising hormone predominance and insulin resistance were demonstrated in 67.8% and 40.7% of the cohort, respectively. Eight-six (95.6%) patients should have also been diagnosed with polycystic ovarian syndrome based on the 2003 Rotterdam new criteria. About 60% of patients who screened positive for insulin resistance had normal fasting serum glucose levels. The same proportion who had full screening for insulin resistance by oral glucose tolerance tests and fasting serum glucose to insulin ratios had discordant results of these two tests. CONCLUSIONS: The 2003 Rotterdam new diagnostic criteria for polycystic ovarian syndrome are generally applicable to the Hong Kong Chinese population. Early detection of insulin resistance in patients with polycystic ovarian syndrome can be ensured by performing an oral glucose tolerance test combined with measurement of fasting serum glucose to insulin ratio.

Calcium supplementation and bone mineral density in postmenopausal women using estrogen replacement therapy.

Both estrogen and calcium have been shown to be of benefit in reducing the incidence of osteoporosis in postmenopausal women. It has been suggested that estrogen promotes the intestinal absorption of calcium, and this effect may especially benefit postmenopausal women with a low dietary intake of calcium. The purpose of this study was to examine the effect of calcium supplementation on the bone mineral density (BMD) of postmenopausal women using estrogen replacement therapy. BMD measurements were made over 12 months in two groups of postmenopausal women, one having treatment with estrogen alone, and the second having estrogen and 1000 mg of supplemental calcium each day. There was no significant reduction in BMD between the two groups over the 12-month study period. Those in the group having supplemental calcium had a significant increase in BMD at the femoral neck (p = 0.023), but not in other areas of the femur nor in the lumbar spine. The results of this study suggest that the addition of supplemental calcium may improve the bone mass of postmenopausal women using estrogen who have a low dietary calcium intake. This benefit appears to be more pronounced in corticocancellous than in trabecular bone, and may therefore have a greater effect on the femoral neck than the lumbar spine.

The effect of continuous combined hormone replacement therapy on arterial reactivity in postmenopausal women with established angina pectoris.

Most epidemiological studies have suggested that the administration of estrogen reduces cardiovascular risk in healthy postmenopausal women. More recently, however, in the large Heart Estrogen/progestin Replacement Study (HERS), it was unexpectedly found that in women with established cardiovascular disease, there was overall no difference in cardiovascular events between those treated with combined oestrogen/progestin hormone replacement therapy and those on placebo. The aim of this study was to examine the effect of combined hormone replacement therapy on arterial reactivity in women with existing angina pectoris. Seventy-four postmenopausal women with angina pectoris were recruited into a 16 week double-blind, placebo-controlled study of treatment with 2 mg of estradiol combined with 1 mg of norethisterone acetate daily. The median endothelium-dependent change in arterial relaxation increased from 5.00 to 7.69% in the treatment group and decreased from 5.57 to 3.64% in the controls. The median endothelium-independent change in arterial relaxation increased from 6.49 to 7.27% in the treatment group and decreased from 4.39 to 2.07% in the controls. The changes in arterial relaxation between the treatment and control groups were not statistically significant. The administration of estrogen/progestin did not significantly improve either endothelium-dependent or -independent arterial relaxation in postmenopausal women with established cardiovascular disease. We have previously shown that estrogen/progestin treatment improves endothelium dependent relaxation in healthy women. The results of our study provide one possible explanation for the clinical findings of the HERS study. In women with established cardiovascular disease, arterial relaxation does not increase significantly in response to treatment with combined hormone replacement therapy.

An examination of the effect of combined cyclical hormone replacement therapy on lipoprotein(a) and other lipoproteins.

Lipoprotein(a) (Lp(a)) is an independent marker of cardiovascular disease which is relatively unresponsive to treatment with most of the commonly prescribed lipid lowering drugs. Concentrations of Lp(a) increase after the menopause, and the primary aim of this study was to determine whether combined hormone replacement therapy was effective in lowering levels of Lp(a) in postmenopausal women. An open longitudinal study was conducted among 42 women who had undergone a spontaneous menopause and were attending the outpatient clinic of the Prince of Wales Hospital, Hong Kong. All subjects were treated with 2 mg oral estradiol daily and 5 mg medroxyprogesterone acetate for 12 days each calendar month. Fasting blood samples for lipoprotein measurement were taken before the commencement of treatment and at 6 and 12 months. Lp(a) levels showed a skewed distribution with a median value before treatment of 9.45 mg/dl (range 1.47-95.62 mg/dl). After 6 months, there was a reduction to 7.70 mg/dl (1.12-72.59 mg/dl) (P < 0.01), and after 12 months the median concentration was 7.14 mg/dl (0.63-69.23 mg/dl) (P < 0.001 0-12 months). There were also significant reductions in the concentrations of apo B from 116.13 to 111.62 mg/dl and LDL-C from 3.02 to 2.74 mmol/l (P < 0.05), plus a lowering of TC of borderline significance. Apo A-I increased from 162.56 to 173.35 mg/dl (P < 0.01), but there were no significant changes in HDL-C or the HDL-C subfractions. TC, LDL-C, apo B and TG concentrations were higher and HDL-C and HDL2-C concentrations were lower when blood was sampled during combined treatment with estrogen and progesterone than when estrogen was being taken alone. Levels of Lp(a) were also lower during the estrogen only phase of treatment, but none of these differences were statistically significant. This study demonstrates that combined cyclical hormone replacement therapy is effective in reducing concentrations of Lp(a). The trend towards a more atherogenic lipid profile during the combined phase of treatment suggests that attention should be given to the timing of blood sampling in future studies of this nature.

The effect of percutaneous oestradiol on atheroma formation in ovariectomized cholesterol-fed rabbits.

OBJECTIVE: The aim of this study was to examine the effect of percutaneous oestradiol on the lipid profile and on atheroma formation using an animal model. METHODS: The study was of 12 weeks duration. Fifty sexually mature female New Zealand White rabbits were divided into five groups of equal size. Two groups acted as controls and received normal rabbit chow. Rabbits in one of these groups were ovariectomized. The remaining three groups were ovariectomized but received 1% cholesterol enriched rabbit chow. One of these cholesterol-fed groups received 0.3 mg/kg percutaneous oestradiol daily whilst another received 0.1 mg/kg oral oestradiol daily. Measurements of concentrations of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were made at the beginning and end of the study. Aortic atheroma formation was measured using computerized image analysis of uptake of Sudan III staining. RESULTS: After 12 weeks there were significant increases in the mean concentrations of TC in the three cholesterol-fed groups compared with controls (P < 0.001). Changes in HDL-C and TG concentrations were less consistent. The mean area of aortic atheroma formation was significantly less in both the percutaneous oestradiol group (4.9%) and the oral oestradiol group (8.6%) compared with the non-oestrogen-treated cholesterol-fed group (19.5%) (P < 0.001, < 0.01 respectively). CONCLUSION: These results suggest that percutaneous oestradiol has a direct protective effect on atheroma formation independent of serum concentrations of total cholesterol.

Misoprostol's effect on uterine arterial blood flow and fetal heart rate in early pregnancy.

OBJECTIVE: To determine whether a single oral dose of misoprostol is associated with change in Doppler resistance indices (RIs) of the uterine artery in early pregnancy. METHODS: Forty pregnant women seeking legal termination of pregnancy at 7-15 completed gestational weeks were each given a single oral dose of 200 microg misoprostol. Resistance indices (A/B ratio) and pulsatility index (PI) of the uterine arteries (UA) and fetal heart rate (FHR) were assessed by Doppler ultrasound before and 1 hour after administration of misoprostol. RESULTS: Doppler RIs (UA-A/B and UA-PI) of the right and left uterine arteries increased significantly 1 hour after misoprostol administration. The right UA-A/B increased from 7.16 +/- 1.09 (mean +/- SEM) to 10.26 +/- 0.67 (P < .001), and the left UA-A/B increased from 7.40 +/- 0.72 to 9.21 +/- 0.82 (P = .04). The right UA-PI increased from 2.38 +/- 0.11 to 2.90 +/- 0.12 (P < .001), and the left UA-PI increased from 2.38 +/- 0.17 to 2.70 +/- 0.18 (P = .03). No significant changes in FHR were noted 1 hour after misoprostol administration. None of the fetuses died during that time. CONCLUSION: Doppler RIs of the uterine arteries increased significantly after single oral doses of misoprostol during the first trimester, implying a reduction in arterial blood flow. Those changes were not associated with fetal death, possibly explaining congenital abnormalities associated with misoprostol in early pregnancy.

The relationship between follicle diameter, fertilization rate, and microscopic embryo quality.

The diameter of preovulatory ovarian follicles was measured at the time of transvaginal US-guided oocyte retrieval, and the oocytes were subsequently examined to assess fertilization rates and the quality of developing embryos. With follicles divided into three groups of increasing diameter, there were no significant differences in the fertilization rates of oocytes recovered from follicles of different size. Embryo quality improved with increasing follicle size, although the differences were not highly significant. Our results demonstrate that an acceptable laboratory outcome can be achieved with oocytes retrieved from smaller sized follicles.

The effect of unilateral versus bilateral tubal cannulation and the number of oocytes transferred on the outcome of gamete intrafallopian transfer.

A comparison of results of GIFT procedures using unilateral and bilateral tubal cannulation was made. There was no difference in outcome between these two methods, with the unilateral approach having some advantages over the bilateral procedure. Pregnancy rates decreased as the number of oocytes transferred was reduced.

Unilateral gamete intrafallopian transfer: the preferred method?

Pregnancy occurred in 8 of 14 patients with the unilateral transfer of three or four oocytes at GIFT procedures. These results suggest that unilateral GIFT may be at least as successful as the bilateral approach. It would appear that unilateral GIFT rather than in vitro fertilization should be used for patients with one normal fallopian tube, and if the pregnancy rates with unilateral GIFT are substantiated, then this would be preferable to the bilateral approach, as operating time is shorter and there is less risk of trauma to the fallopian tubes at the time of gamete transfer.

Changes in atherogenic lipids and lipoproteins during natural and hyperstimulated cycles in healthy women.

OBJECTIVE: To compare changes in the concentrations of Lp(a) lipoprotein and other atherogenic lipids and lipoproteins in natural and hyperstimulated ovarian cycles. DESIGN: Open, prospective study. SETTING: Academic department in a teaching hospital. PATIENT(S): Normal ovulatory women served as controls and the treatment group consisted of women undergoing ovarian hyperstimulation. INTERVENTION(S): The treatment group received hMG on a fixed regimen. MAIN OUTCOME MEASURE(S): Measurements of serum lipids and lipoproteins were made in both natural and hyperstimulated cycles. RESULT(S): There was a significant increase in the median concentration of Lp(a) lipoprotein from 10.1 to 10.7 mg/dL in the luteal compared with the proliferative phase of unstimulated cycles. In hyperstimulated cycles, there was a significant increase in the median concentration of Lp(a) lipoprotein from 9.7 mg/dL in the proliferative phase to 11.3 mg/dL in the luteal phase. Reductions in concentrations of total cholesterol and low-density lipoprotein cholesterol were found in the luteal phase of hyperstimulated cycles. CONCLUSION: Concentrations of Lp(a) lipoprotein increase during the luteal phase of both natural and hyperstimulated ovarian cycles.

Spontaneous abortion: a randomized, controlled trial comparing surgical evacuation with conservative management using misoprostol.

OBJECTIVE: To compare the efficacy of surgical evacuation of the uterus with medical evacuation using misoprostol in cases of spontaneous abortion. DESIGN: A prospective, randomized, controlled trial. SETTING: A university teaching hospital. PATIENT(S): Six hundred thirty-five women who aborted spontaneously and who consented to pretreatment randomization. INTERVENTION(S): Routine surgical evacuation or medical evacuation of the uterus using misoprostol. MAIN OUTCOME MEASURE(S): Immediate, short-term (2-3 weeks), and medium-term (6 months) medical complications. RESULT(S): There was a significantly lower incidence of immediate and short-term complications in the group treated with misoprostol compared with the surgically treated group. There were also fewer major complications in the 6 months after treatment in the medically treated group. Approximately 50% of the medically treated group subsequently required surgical evacuation, and these subjects required significantly more analgesia. CONCLUSION(S): Treatment with misoprostol can reduce the demand for surgical evacuation in cases of spontaneous abortion, and its use is associated with fewer medical complications.

Prospective, randomized, controlled study of the effect of hormone replacement therapy on peripheral blood flow velocity in postmenopausal women.

OBJECTIVE: To investigate the effect of different types and methods of delivery of hormone replacement therapy (HRT) on peripheral vascular flow velocity in postmenopausal women. DESIGN: A prospective, randomized, operator-blinded, controlled study. SETTING: A hormone replacement clinic in a university teaching hospital. PATIENT(S): Sixty-eight women who had undergone surgical menopause. INTERVENTION(S): No treatment, oral estrogen, continuous combined estrogen and progestogen, or percutaneous estrogen. MAIN OUTCOME MEASURE(S): The pulsatility indices of the brachial, dorsalis pedis, popliteal, and radial arteries were measured under standardized conditions before the commencement of HRT and after 2 and 6 months of treatment. Serum E2 levels were measured at each visit. RESULT(S): There was an inverse correlation between the serum E2 levels and the pulsatility indices. There was a significant reduction in the pulsatility index in at least one of the four arteries after 2 months of HRT in all the treatment groups but not in the control group. The effect of HRT on the pulsatility index persisted until the completion of the study in all the treatment groups. CONCLUSION(S): These results confirm that the administration of HRT is associated with a reduction of the pulsatility index, and hence an increase in blood flow in the peripheral arteries; this change in the pulsatility index is related directly to serum E2 levels. The percutaneous route of administration of estrogen was at least as effective as oral treatment in improving peripheral vascular flow velocity. The beneficial effect of estrogen was not affected by the addition of a progestogen.

Psychiatric morbidity following miscarriage: a prevalence study of Chinese women in Hong Kong.

OBJECTIVE: Previous studies reported that 48-51% of women in Western countries developed depressive disorder following a miscarriage. There is, however, little data among non-Western populations. The aim of this study was to measure the prevalence of psychiatric morbidity following miscarriage among Chinese women in Hong Kong. METHODS: Subjects were interviewed immediately after a miscarriage to collect medical, psychiatric, and sociodemographic data. Six weeks following the miscarriage, 150 subjects were assessed with the Structured Clinical Interview for DSM-III-R (SCID) to establish psychiatric diagnoses. RESULTS: 18 subjects (12%) met the DSM-III-R criteria for major depression and 2 subjects (1.3%) were diagnosed anxiety disorder NOS six weeks after the miscarriage. CONCLUSIONS: Chinese women in Hong Kong have a lower rate of psychiatric morbidity after a miscarriage.

Dietary calcium intake in postmenopausal Chinese women.

Dietary calcium intake has been shown to vary both between and within populations. The aim of this study was to compare two methods of assessment of dietary calcium in the local population of postmenopausal Chinese women. The intake was measured using 24h dietary recall as well as a food frequency questionnaire. There was a high correlation in the measurement of calcium intake between these methods. The mean daily intake in postmenopausal women not taking calcium supplementation was 397.6 mg assessed using 24 h recall, and 390.9 mg according to the food frequency questionnaire. There was no evidence of a difference in the reproducibility of the results given by the two methods. The dietary intake of calcium in postmenopausal Chinese women is below the recommended daily allowance for adult females in East Asia, and coupled with other factors may predispose to the development of osteoporotic fractures.