Low density lipoprotein receptor-related protein 5 gene polymorphisms and osteoporosis in Thai menopausal women.

BACKGROUND: Osteoporosis, characterized by low bone mineral density (BMD) and high bone fracture risk, is prevalent in Thai menopausal women. Genetic factors are known to play a key role in BMD. Low density lipoprotein receptor-related protein 5 (LRP5), a co-receptor in the Wnt/beta-catenin pathway, is involved in many aspects of bone biology. As coding single nucleotide polymorphisms (cSNPs) of LRP5, including A1330V (rs3736228), and Asian-related Q89R (rs41494349) and N740N (rs2306862), are associated with lowered BMD, this study aimed to determine the relationship between these LRP5 polymorphisms and BMD in 277 Thai menopausal women. RESULTS: Only rs3736228 deviated from the Hardy-Weinberg equilibrium of allele frequency (p = 0.022). The median, range and p value for the BMD related to each SNP parameter were compared (Mann-Whitney U test). Significant differences were observed between wild-type and risk alleles for both rs3736228 (total radial, p = 0.011; and radial 33, p = 0.001) and rs2306862 (radial 33: p = 0.015) SNPs, with no significant difference for rs41494349 SNP. Linkage disequilibrium was strong for both rs3736228 and rs2306862 SNPs. Haplotype analysis identified high CC frequency in both normal and osteopenia/osteoporosis groups, with a significant odds ratio for carrying the TT haplotype; however, this was non-significant after adjusting for age. Multivariate binary logistic regression analysis performed for rs3736228 showed that individuals with a body mass index <25 kg/m(2) had an increased risk of osteoporosis for each decade, but the polymorphism had no effect. CONCLUSIONS: This study did not identify LRP5 polymorphisms as a risk factor for osteoporosis in Thai menopausal women. Further studies with larger sample sizes are needed to further clarify the role of LRP5 as a genetic determinant of osteoporosis.

ID4 gene polymorphism and osteoporosis in Thai menopausal women.

BACKGROUND: The inhibitor of DNA binding 4 (ID4) protein regulates osteogenic and adipogenic cell fate and lack of lD4 gene expression decreased osteoblast differentiation. Variant in the ID4 gene polymorphism has not been reported with osteoporosis. OBJECTIVE: To identify whether ID4 can be a marker gene for osteoporosis in Thai menopausal women. MATERIAL AND METHOD: The 3 'UTR of lD4 (rs3798339) single nucleotide polymorphism was examined bypolymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP), together with lumbar spine bone mineral density (BAMD) in 160 Thai menopausal women. RESULTS: Lumbar spine 3 (L3) had a significantly lower BMD score in women with the TT genotype, compared with the CT+CC genotypes (p = 0.037). This disappeared after the adjustment of various factors. CONCLUSION: The polymorphism at 3'UTR of lD4 gene can alter ID4 mRNA stability, and may be linked to the function of proteins. However, this needs confirmation in larger populations. The present study is useful as an initial investigation into ID4 gene polymorphism in osteoporosis.

Association of MTHFR C677T polymorphism with bone mineral density of osteoporosis in postmenopausal Thai women.

BACKGROUND: Osteoporosis and osteopenia is rising with the increase in numbers of postmenopausal women. Methylenetetrahydrofolate reductase (MTHFR), a homocysteine catabolizing enzyme, is involved in the regulation of bone mineral density (BMD). The association between MTHFR C677T polymorphism with osteoporosis in postmenopausal Thai women is hitherto unclear. OBJECTIVE: To investigate the association between MTHFR C677T and BMD in postmenopausal Thai women. MATERIAL AND METHOD: The study subjects consisted of 346 postmenopausal Thai women volunteers. Standard dual-energy X-ray absorptiometry (DXA) was used for measurement of BMD T-score. Restriction fragment length polymorphism (RFLP) analysis was used for measurement of MTHFR C677T polymorphism. RESULTS: In the evaluation of 346 postmenopausal Thai women heterozygous (CT) genotype had a risk of osteopenia than normal control (odds ratio (OR) = 5.66, p < 0.001). BMD T-scores at each bone position revealed that heterozygous (CT) genotype had increased risk of osteopenic bones than normal controls at lumbar spines 1, 2, and 4 (OR = 2.48, p < 0.001, OR = 1.98, p = 0.008 and OR = 1.83, p = 0.016 respectively), ward's triangle (OR = 2.08, p = 0.008), and head of radius (OR = 2.95, p = 0.008). CONCLUSION: These results indicate the possibility of using MTHFR C677T polymorphism to identify postmenopausal Thai women at high risk of osteopenia.

Hypomethylation of Alu elements in post-menopausal women with osteoporosis.

A decrease in genomic methylation commonly occurs in aging cells; however, whether this epigenetic modification leads to age-related phenotypes has not been evaluated. Alu elements are the major interspersed repetitive DNA elements in humans that lose DNA methylation in aging individuals. Alu demethylation in blood cells starts at approximately 40 years of age, and the degree of Alu hypomethylation increases with age. Bone mass is lost with aging, particularly in menopausal women with lower body mass. Consequently, osteoporosis is commonly found in thin postmenopausal women. Here, we correlated the Alu methylation level of blood cells with bone density in 323 postmenopausal women. Alu hypomethylation was associated with advanced age and lower bone mass density, (P<0.05). The association between the Alu methylation level and bone mass was independent of age, body mass, and body fat, with an odds ratio [1]  = 0.4316 (0.2087-0.8927). Individuals of the same age with osteopenia, osteoporosis, and a high body mass index have lower Alu methylation levels (P = 0.0005, 0.003, and ≤0.0001, respectively). Finally, when comparing individuals with the same age and body mass, Alu hypomethylation was observed in individuals with lower bone mass (P<0.0001). In conclusion, there are positive correlations between Alu hypomethylation in blood cells and several age-related phenotypes in bone and body fat. Therefore, reduced global methylation may play a role in the systemic senescence process. Further evaluation of Alu hypomethylation may clarify the epigenetic regulation of osteoporosis in post-menopausal women.

Association of Thr420Lys polymorphism in DBP gene with fat-soluble vitamins and low radial bone mineral density in postmenopausal Thai women.

AIMS: To investigate the genetic markers for osteoporosis bone mineral density by the genotyping of rs7041, rs4588 and rs1352845 in the DBP gene with either bone mineral density or serum 25-hydroxycholecalciferol, retinol and α-tocopherol, among 365 postmenopausal Thai women. MATERIALS & METHODS: The DBP genotypes were analyzed by a PCR restriction fragment-length polymorphism method. Serum 25-hydroxycholecalciferol was assessed using a commercial chemiluminescent immunoassay. Serum retinol and α-tocopherol were measured by reverse-phase high-performance liquid chromatography. RESULTS: After adjustment for age >50 years, elder Thai subjects with low BMI (≤25 kg/m(2)) and carrying the rs4588 CC genotype had a higher risk of radial bone mineral density osteoporosis (odds ratio: 6.29; p = 0.048). The rs1352845 genotype also had a statistical association with total hip bone mineral density; however, it disappeared after adjustment for age and BMI. No association was found in fat-soluble vitamins with bone mineral density. CONCLUSION: DBP genotypes may influence the osteoporosis bone mineral density in postmenopausal Thai women.

Decreased retinol transport proteins in Thai post-menopausal women with osteoporosis.

High vitamin A ingestion or high serum retinol have been postulated to increase the risk of fractures and osteoporosis by reduced bone mineral density (BMD). Retinol is carried and transported to the tissues bound to retinol binding protein 4 (RBP4) and transthyretin (TTR). The relationships between retinol, retinol transport protein, retinol binding protein 4 (RBP4) and transthyretin (TTR) and BMD and osteoporosis are unclear. To examine the association between retinol and RBP4 and TTR and osteoporosis, 73 osteoporotic and 71 normal Thai postmenopausal women were studied. RBP4 and retinol levels did not differ between the groups. Serum TTR was significantly higher in control than osteoporotic subjects (89.47 and 144.53 microg/ml, respectively, p = 0.003, Mann-Whitney U test). TTR was positively correlated with BMD at several sites, such as the total radius bone (r = 0.172, p = 0.008, Spearman rank test). Osteoporosis risk was analyzed with binary logistic regression. Lean elderly Thais with lower TTR levels had a higher risk of osteoporosis. RBP4 and retinol levels had no relationship with disease status among Thai post-menopausal women. These results suggest calcium, minerals, vitamins and the retinol transport protein, transthyretin may be involved in the pathogenesis of osteoporosis.

Hysteroscopic rollerball endometrial ablation as an alternative treatment for adenomyosis with menorrhagia and/or dysmenorrhea.

AIM: The aim of this study was to assess the long-term effectiveness and safety of hysteroscopic rollerball endometrial ablation as a surgical management of adenomyosis with menorrhagia and/or dysmenorrhea. We compared the results of patients who underwent pretreatment with gonadotropin-releasing hormone (GnRH) agonist with the results of those who did not. METHODS: A retrospective study included 190 adenomyotic patients who suffered from menorrhagia and/or dysmenorrhea and underwent hysteroscopic rollerball endometrial ablation. Main outcome measures were rates of successful operation, complications, improvement of abnormal uterine bleeding and pelvic pain after the surgery. RESULTS: The majority of the patients (142, 74.7%) underwent hysteroscopic rollerball endometrial ablation during the early proliferative phase of the menstrual cycle. The rest were operated on after GnRH agonist pretreatment for 6-8 weeks. Ablations were successfully performed on all patients in a day surgery setting. The average operation time was 36.3 ± 7.1 min. The mean glycine deficit was 583.4 ± 247.3 mL. The ablation in the no-pretreatment group took a significantly longer time and had more glycine absorption compared to the GnRH agonist pretreatment group (P < 0.0001). Mean postoperative follow-up duration was five years (range 1-10 years). A total of 187 patients (98.4%) who had undergone hysteroscopic endometrial ablation reported decreased bleeding: amenorrhea in 58 (30.5%), hypomenorrhea in 78 (41.1%), and eumenorrhea in 51 (26.8%) patients. Three patients (1.6%) underwent hysterectomy due to symptoms recurrence. A total of 165 (86.8%) patients with dysmenorrhea reported either reduced or no dysmenorrhea. There was no significant difference in the efficacy of hysteroscopic rollerball endometrial ablation between patients who underwent pretreatment with GnRH agonists and those who did not. No major complications related to the procedure were reported. CONCLUSIONS: Hysteroscopic rollerball endometrial ablation as a surgical management of menorrhagia and dysmenorrhea that develops in patients with adenomyosis is an effective and safe procedure. It can reduce the need for the unnecessary major surgery of hysterectomy.

Research publication by the Royal Thai College of Obstetricians and Gynecologists residency training program, 1994-2003.

OBJECTIVE: To evaluate the impact of the manuscript requirement policy on research publications from the Royal Thai College of Obstetricians and Gynecologists (RTCOG) residency training program. MATERIAL AND METHOD: Names and research titles of RTCOG residents from 1994 to 2003 were used to search for publications in the Medline system and Thai Index Medicus. RESULTS: There were 759 residents with 188 (24.8%) articles published. The publications per year varied from 4.8% to 17.0%. Residents were the first authors of 75 articles (39.9%). One hundred and thirteen articles (60.11%) were published in local medical journals. The majority of articles published in international journals (65.3%) were published in the Journal of the Medical Association of Thailand. After initiation of the publication promotion policy in 1999, the number of publications in which residents were not the first authors increased from 39.8% to 60.2%. CONCLUSION: The manuscript requirement policy can maintain the research publication rate.

A randomized comparison of vaginal misoprostol and dinoprostone for cervical priming in nulliparous women before operative hysteroscopy.

OBJECTIVE: To compare the efficacy and side effects of vaginal misoprostol with dinoprostone for cervical priming before operative hysteroscopy and to assess the cervicouterine complications related to cervical dilatation and hysteroscopic surgery. DESIGN: A prospective randomized study. SETTING: Tertiary university hospital. PATIENT(S): Three hundred ten nulliparous women with definite intrauterine lesions. INTERVENTION(S): Hysteroscopic surgery of intrauterine lesions. MAIN OUTCOME MEASURE(S): Cervical response, outcome, complications of hysteroscopic surgery, and side effects of both drugs. RESULT(S): Among the 310 patients recruited, 152 were randomized to the vaginal misoprostol group and 158 to the dinoprostone group. Mean cervical dilatation, cervical dilatation rate, and mean time for cervical dilatation to Hegar 9 were significantly different between the misoprostol group (7.4 +/- 0.8 mm, 70.4%, and 39.5 +/- 18.8 seconds, respectively) and the dinoprostone group (7.0 +/- 0.9 mm, 80.4%, and 43.6 +/- 17.1 seconds, respectively). Cervical tearing during hysteroscopic surgery occurred in 3 patients (2.0%) in the misoprostol group and in 12 patients (7.6%) in the dinoprostone group. There were more side effects in the misoprostol group. The significant difference of side effects between the two groups were abdominal pain, vaginal bleeding, and feeling feverish, which occurred in 36.2%, 29.6%, and 7.2% in the misoprostol group compared to 21.5%, 16.5%, and 1.3%, respectively, in the dinoprostone group. CONCLUSION(S): Vaginal misoprostol is more effective than dinoprostone for cervical priming in nulliparous women before hysteroscopic surgery. Although more side effects occurred in the misoprostol-treated patients, they were mild. We suggest using vagina misoprostol for cervical priming instead of dinoprostone.

Hysteroscopic polypectomy in 240 premenopausal and postmenopausal women.

OBJECTIVE: To ascertain the therapeutic efficacy and safety of hysteroscopic polypectomy in 240 premenopausal and postmenopausal patients. DESIGN: Retrospective study. SETTING: Tertiary university hospital. PATIENT(S): Two hundred forty patients with intrauterine endometrial polyps, who mostly suffered from abnormal uterine bleeding and infertility. INTERVENTION(S): Hysteroscopic polypectomy using various instruments including microscissors, grasping forceps, or electrosurgery either with a monopolar probe or a resectoscope. MAIN OUTCOME MEASURE(S): Operating time, amount of glycine absorption, complications, resumption of normal menstruation, cumulative pregnancy rate, and recurrent rate of polyps after hysteroscopic surgery. RESULT(S): Resectoscopic polypectomy needed more operating time, had more glycine absorption and complications, but less recurrence than other hysteroscopic techniques. The resectoscope had a 0% recurrence rate and that grasping forceps had a 15% recurrence rate. A total of 21 (8.7%) complications occurred, but no major complications were noted. After long-term follow-up of 9 years and 2 months, those with abnormal uterine bleeding resumed normal menstruation in 93.1% and those with infertility had a cumulative pregnancy rate of 42.3%. There was no statistical difference in reproductive outcome between patients having polyps < or = 2.5 cm and >2.5 cm. CONCLUSION(S): We found hysteroscopic polypectomy to be effective, safe, minimally invasive procedure with low rate and mild complications. Restoration of reproductive ability did not depend on the size of the removed lesion. Resectoscopic surgery is more preferable to prevent recurrence of polyps.

Role of hysteroscopy in modern gynaecology.

In only a few years, operative hysteroscopy has become very popular among gynecologists, whereas more than a century passed before diagnostic hysteroscopy attained wide acceptance. At present, with the development of miniaturized cameras, this endoscopic operative technique can be used in the management of all non-cancerous intrauterine lesions, with the entire procedure being performed under video monitoring. In this chapter we will review the present indications of diagnostic hysteroscopy and also report our results of hysteroscopic submucous myomectomy, polypectomy, adhesiolysis, septoplasty, and endometrial ablation.

A prospective comparative study between hysterosalpingography and hysteroscopy in the detection of intrauterine pathology in patients with infertility.

AIM: To investigate the accuracy of hysterosalpingography (HSG) in comparison to hysteroscopy in the detection of intrauterine pathology in patients with infertility, where hysteroscopy is the gold standard. METHODS: A prospective, comparative study included 336 patients undergoing both HSG and diagnostic hysteroscopy. Main outcome measures were sensitivity, specificity, positive and negative predictive value, and accuracy rate of HSG. RESULTS: Intrauterine abnormalities were shown on HSG in 286 patients and confirmed in 200 at hysteroscopy. Contrarily intrauterine lesions were detected by hysteroscopy in 4 out of 50 patients in whom HSG were normal. The most common intrauterine finding of 336 patients on hysteroscopy were intrauterine adhesions (IUA) (74), followed by endometrial polyps (56), and submucous myoma, 26 patients. Statistical analysis revealed that HSG in the detection of intrauterine pathology had a sensitivity of 98.0%, specificity of 34.9%, positive predictive value of 69.9%, negative predictive value of 92.0%, and accuracy rate of 73.2% with false-positive and false-negative rates of 30.1% and 8.0%, respectively. The common incorrect diagnoses of HSG were misdiagnosing a condition of cervical stenosis as severe IUA in 24 patients, endometrial polyps as submucous myoma in 22 out of 50 patients, and submucous myoma as endometrial polyps in 12 out of 72 patients. CONCLUSIONS: Hysterosalpingography is still a useful screening test for the evaluation of the uterine cavity. If a hysterogram demonstrates intrauterine abnormalities, hysteroscopy should be considered to make a definite diagnosis and treatment. Both procedures should be complementary to each other.