Menopausal hormonal therapy in surgically menopausal women with underlying endometriosis.

OBJECTIVE: This study aimed to investigate the relationship between menopausal hormone therapy (MHT) and endometriosis recurrence in women who underwent hysterectomy with bilateral salpingo-oophorectomy to treat endometriosis. METHOD: This retrospective cohort study included 330 women who underwent definitive surgery to treat endometriosis during 1996-2012. Follow-up data until December 2018 were analyzed. Patients were grouped as MHT non-users (non-MHT, n = 43), estrogen-only therapy (ET, n = 230), estrogen-progestogen therapy (EPT, n = 39) and tibolone (n = 18). RESULTS: The mean age at surgery was 41.5 ± 5.3 years. The overall median follow-up duration was 6.0 years (interquartile range [IQR]: 3.0-10.4), and the median duration of MHT use was 66.0 months (IQR: 36.0-116.3). The overall recurrence rate was 3.0% (95% confidence interval: 1.5-5.5) and there was no significant difference in recurrence among the study groups. Disease recurrence resolved after MHT discontinuation, or change in MHT type and/or dose. CONCLUSIONS: No significant association between MHT use and endometriosis recurrence was found in this study. The endometriosis recurrence rate was non-significantly different between ET and EPT. Recurrent endometriosis can be successfully treated without invasive measures. No study patients had malignant transformation after a median follow-up of 6 years. Our findings suggest that any of the three evaluated MHT regimens can be used in surgically menopausal Thai women with underlying endometriosis.

Impact of Global Consensus Statement on compliance with hormonal therapy for surgical menopause.

OBJECTIVE: Initiation of and compliance with menopausal hormonal therapy (MHT) have been dropping due to the 2002 Women's Health Initiative (WHI) publication. We evaluated the change in practice of MHT for surgical menopause after implementing the 2013 'Global Consensus Statement on MHT' to our institutional guideline. METHODS: A retrospective study was conducted in surgically menopausal women newly registering at the Siriraj Menopause Clinic in a university hospital, Thailand, from 1995 to 2013. The patients were categorized into four groups according to periods of MHT initiation: 1995-1998 (control), 2000-2003 (WHI affected), 2005-2008 (post WHI) and 2010-2013 (Global Consensus Statement affected). Their 3-year compliance with MHT was compared using forward stepwise regression analysis. RESULTS: There were 288, 156, 107 and 104 cases in the 1995-1998, 2000-2003, 2005-2008 and 2010-2013 groups. Their mean age at surgery was 42.8 ± 4.7 years. After the first, second and third years, overall compliance was 82.4%, 70.9% and 61.2%, respectively. The 3-year compliance drastically dropped in the 2000-2003 group, and then improved to control level in the 2010-2013 group (51.9% vs. 77.9%, p = 0.035). CONCLUSION: The initiation of MHT continuously dropped during 2000-2013; however, compliance with MHT initiated during 2010-2013 improved after implementing the 2013 'Global Consensus Statement on MHT' to our institutional guideline. Each institute should have a strategy to encourage the initiation of and compliance with MHT for surgical menopause to achieve long-term health benefits.

Validation of osteoporosis risk assessment tools in middle-aged Thai women.

OBJECTIVES: To validate osteoporosis risk assessment tools in middle-aged Thai women. METHODS: A total of 1038 women who had bone mineral density (BMD) measurements using dual-energy X-ray absorptiometry were reviewed. Clinical data were used to validate the diagnostic test performance of various osteoporosis risk assessment tools, including ABONE, FRAX®, ORAI, OSIRIS, SCORE, SOFSURF, and OSTA. The following parameters were evaluated: sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy; those with 95% confidence interval (CI) of the receiver operator characteristics area under the curve (ROC-AUC) > 0.5 were considered statistically significant. RESULTS: The subjects had a mean age of 53.01 ± 6.20 years and body mass index (BMI) of 23.98 ± 3.38 kg/m2. Among the osteoporosis risk assessment tools being evaluated, the tools that had ROC-AUC >0.8 and 95% CI >0.5, and could predict osteoporosis at the femoral neck with high specificity of >75% and NPV of >90%, were FRAX® without BMD (ROC-AUC 0.83; 95% CI 0.73-0.93; specificity 99.90; NPV 98.89), SCORE (ROC-AUC 0.86; 95% CI 0.78-0.94; specificity 98.79; NPV 98.99), and OSTA (ROC-AUC 0.86; 95% CI 0.79-0.94; specificity 75.03; NPV 99.73). CONCLUSION: The prevalence of osteoporosis in the middle-aged Thai women attending Siriraj Menopause Clinic is 7.3% at the lumbar spine and/or femoral neck. FRAX® without BMD, SCORE, and OSTA have appropriate validity as tools for ruling out osteoporosis in these women.

Cimicifuga racemosa extract for relieving menopausal symptoms: a randomized controlled trial.

OBJECTIVES: To evaluate the effectiveness of black cohosh extract 40 mg/day for relieving moderate to severe menopausal symptoms and improving quality of life in Thai women. METHODS: A randomized, double-blind, placebo-controlled clinical trial was conducted in a menopause clinic of a tertiary-care university hospital during 2011-2013. Participants were peri- or postmenopausal Thai women aged at least 40 years, who have moderate to severe menopausal symptoms evaluated using the Kupperman index (KI). Outcome measures included KI, frequency of hot flushes, Menopause-Specific Quality of Life (MENQOL) score, participants' global satisfaction and safety outcomes. RESULTS: There were 54 participants assigned to treatment (black cohosh extract 40 mg/day, n = 27) or placebo group (n = 27). Both the treatment and placebo groups had comparable baseline KI scores (33.9 ± 7.9 vs. 31.3 ± 6.8), frequency of hot flushes (3.1 ± 2.0 vs. 2.8 ± 2.1), and MENQOL scores, all of which improved with time. Neither the improvements nor the global satisfaction were significantly different between the two groups; but the proportion of participants with moderate to severe symptoms seemed to be lower in the treatment group than in the placebo group (40% vs. 60%, p = 0.174). There was no serious adverse event or significant change in liver function tests. CONCLUSIONS: A black cohosh extract of 40 mg/day is not superior to a placebo for relieving moderate to severe menopausal symptoms or improving quality-of-life scores in Thai women.

Development and validation of the Menopause-specific Quality of Life Scale for menopausal Thai women.

OBJECTIVES: To develop a new instrument, the Menopause-specific Quality of Life Scale (MS-QoLS), for Thai women and to study the experience of menopausal aspects in peri- and postmenopausal Thai women. MATERIALS AND METHODS: Item generation was developed from a focus group discussion and in-depth interview, and the content validity index (CVI) was computed, using item relevance ratings by content experts. Items with CVI values higher than 0.7 were selected. The draft questionnaire was tested for language, format and content. The final questionnaire was administered and the construct validity and reliability were then assessed. RESULTS: Fifty-seven peri- and postmenopausal women participated in the focus group discussion and in-depth interview. Sixty-eight items across eight dimensions were generated based on content analysis result. The dimensions included Physical health, Psychological health, Sexual health, Daily activity, Family, Social, Treatment, and Economics. A total of 280 menopausal women were recruited from four collaborative hospitals for psychometric validation. After factor analysis, 22 items remained with six dimensions identified, that is, well-being, emotionality, anxiety/fear, family, social and sexual health. Cronbach's coefficient α of each domain was between 0.61 and 0.83. CONCLUSION: The Thai MS-QoLS was systematically developed and validated for peri- or postmenopausal women. The initial assessment of the questionnaire showed an acceptable level of validity and reliability.

Predictors for metabolic syndrome in perimenopausal and postmenopausal Thai women.

OBJECTIVE: To determine the prevalence and predictors of metabolic syndrome in perimenopausal and postmenopausal Thai women. MATERIALS AND METHODS: The cross-sectional study was carried out in the Siriraj Menopause Clinic, Faculty of Medicine Siriraj Hospital, Mahidol University, a tertiary-care university hospital, from May 2006 to August 2009. Metabolic syndrome was diagnosed using the International Diabetes Federation (IDF) criteria for an Asian population, the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria with Asian waist circumference, and the NCEP-ATP III with body mass index cut-off value. The outcome measures were the prevalence and predictors of metabolic syndrome in perimenopausal and postmenopausal Thai women. RESULTS: There were 971 women classified into perimenopausal (n = 331), naturally postmenopausal (n = 442) and surgically postmenopausal (n = 198) groups. The overall prevalences (95% confidence interval, CI) of metabolic syndrome were 16.0% (15.1-24.3%), 15.9% (13.6-18.2%), and 14.9% (14.0-19.8%) by IDF criteria, modified NCEP-ATP III criteria with Asian waist circumference, and with body mass index cut-off value, respectively. Focusing on the NCEP-ATP III criteria with Asian waist circumference, the prevalence was the highest in the surgically postmenopausal group (19.7%, 95% CI 15.1-24.3%) followed by the perimenopausal (12.4%, 95% CI 9.4-15.4%) and naturally postmenopausal (16.9%, 95% CI 14.0-19.8%) groups, but without statistical significance. The prevalence increased with age, body mass index and family history of cardiovascular disease. CONCLUSION: The overall prevalence of metabolic syndrome in perimenopausal and postmenopausal Thai women is 14.9-16.0%, depending on diagnostic criteria, and its significant predictors include age, body mass index, and family history of cardiovascular disease.

No additional benefit of shortwave diathermy over exercise program for knee osteoarthritis in peri-/post-menopausal women: an equivalence trial.

OBJECTIVE: To evaluate the benefit of shortwave diathermy (SWD) supplemented to an exercise program for knee osteoarthritis (OA) in peri-/post-menopausal women. METHODS: A double-blind randomized placebo-controlled equivalence trial was conducted in a university hospital. Participants including 113 women aged 50-85 years with primary knee OA were instructed to do regular quadriceps exercise, and randomized to control (n=60) and treatment (n=53) groups receiving sham SWD and therapeutic SWD, respectively. The treatment being evaluated was continuous SWD, 20 min/session, 3 sessions/week for 3 weeks. The outcomes including Thai Western Ontario and McMaster Universities OA (WOMAC) index, 100-m walking speed, stair ascent-and-descent time, global assessment, patient's satisfaction, and adverse events were assessed at baseline and end of treatment. RESULTS: At the end of treatment, both groups had trivial but statistical improvement in all outcomes. Intention-to-treat analysis showed no statistically significant difference between the two groups in all outcomes. Per protocol analysis demonstrated the equivalence in Thai WOMAC total score, as the 95% confidence interval of difference (-0.62, 0.92) was within confidence limits of +/-1cm. CONCLUSION: The addition of SWD to an exercise program for knee OA in peri-/post-menopausal women is not superior to the exercise program alone.

Sulfogalactosylglycerolipid is involved in human gamete interaction.

Recent results from our laboratory have revealed the role of sulfogalactosylglycerolipid (SGG) in mouse sperm-zona pellucida (ZP) binding. In this report, we demonstrated the presence of SGG in Percoll-gradient centrifuged (PGC) human sperm by high performance thin layer chromatography with orcinol and Azure A staining, specific for glycolipids and sulfolipids, respectively. SGG in human PGC sperm was quantified by its affinity to Azure A to be 12-15 mol% of sperm lipids. Indirect immunofluorescence revealed that SGG existed on both live and aldehyde fixed human sperm in the head region. Pretreatment of human PGC sperm with affinity purified antiSGG Fab markedly inhibited sperm binding to the ZP in a concentration dependent manner, without any changes in the spontaneous acrosome rate or sperm motility parameters. Fluorescently labeled SGG liposomes also bound uniformly to isolated human ZP, while fluorescently labeled galactosylglycerolipid (GG, SGG's parental lipid) or phosphatidylserine (PS, negatively charged like SGG) liposomes did not. All of these results suggested the role of human sperm SGG in ZP binding.

Anti-SLIP1-reactive proteins exist on human spermatozoa and are involved in zona pellucida binding.

Sulpholipid immobilizing protein 1 (SLIP1) is an evolutionarily conserved 68 kDa plasma membrane protein, present selectively in germ cells. We have previously shown that mouse sperm SLIP1 is involved in sperm-zona pellucida (ZP) binding. In this report, we extended our study to the human system. Immunoblotting demonstrated that anti-SLIP1-reactive proteins (mol. wt 68 and 48 kDa) could be extracted from human spermatozoa by an ATP-containing solution, a result that is consistent with observations in other species. Direct immunofluorescence, using Cy3-conjugated anti-SLIP1 IgG, revealed SLIP1 staining over the acrosomal region, with higher intensity at the posterior area. Using the human sperm-ZP binding assay, we demonstrated that pretreatment of human spermatozoa from three donors with anti-SLIP1 IgG revealed lower numbers of zona-bound spermatozoa, as compared to the corresponding control spermatozoa treated with normal rabbit serum IgG. This decrease in zona pellucida binding was not from an antibody-induced decline in sperm motility or an increase in the premature acrosome reaction. The results strongly suggest that anti-SLIP-reactive proteins on human spermatozoa play an important role in ZP binding.

Embryonic testicular regression syndrome: a case report.

A case of testicular regression syndrome was reported. The patient was an 18 year old girl presenting with primary amenorrhoea. Physical examination revealed normal female external genitalia and underdeveloped secondary sexual characteristics. Hormonal profile indicated gonadal failure. Chromosome analysis revealed 46,XY karyotype. Diagnostic laparoscopy demonstrated undeveloped internal genital organs. Remnants of epididymis, vas deferens and seminiferous tubule were uncovered during exploratory laparotomy. Ontogeny of sexual differentiation and pathogenesis of testicular regression syndrome were reviewed and discussed.

Lack of correlation between oocyte-corona-cumulus complex morphology and nuclear maturity of oocytes collected in stimulated cycles for intracytoplasmic sperm injection.

OBJECTIVE: To evaluate the usefulness of morphology grading of the oocyte-corona-cumulus complex (OCCC) as a marker of oocyte nuclear maturity, fertilizability, embryo cleavage, and likelihood of pregnancy. DESIGN: Prospective cohort study. SETTING: Academic fertility center. PATIENT(S): Eighty-three infertile couples undergoing IVF-ET/intracytoplasmic sperm injection treatment. INTERVENTION(S): All patients underwent a long stimulation protocol of GnRH agonist therapy followed by hMG administration and transvaginal oocyte recovery. MAIN OUTCOME MEASURE(S): All OCCCs, oocytes, and embryos were assessed. The relation among OCCC morphology and the nuclear maturity of denuded oocytes, the fertilization rate, and embryo development to the cleavage stage were analyzed. RESULT(S): Of 909 OCCCs collected from 92 cycles, 2.5%, 4.2%, 79.9%, and 13.4% were prophase I, metaphase I, metaphase II, and degenerating, respectively. No statistically significant differences were found in the percentage of intact metaphase II oocytes, the fertilization rate, or the cleavage rate among complexes with different morphologic grades. The morphologic grade of the OCCCs of transferred embryos in the pregnant group was not different from that in the nonpregnant group. CONCLUSION(S): Most oocytes were in metaphase II at the time of retrieval after ovarian stimulation. However, no relation was observed between the OCCC morphologic grade and oocyte nuclear maturity, the fertilization rate, or embryo cleavage. These observations suggest that OCCC morphology grading is a poor marker of oocyte quality.

Isolation of antiSLIP1-reactive boar sperm P68/62 and its binding to mammalian zona pellucida.

Single-step purification of boar sperm P68/62 that is cross-reactive with a polyclonal antibody against sulfolipidimmobilizing protein 1 (SLIP1) was achieved by chromatofocusing. This method is useful for obtaining P68/62 in quantity. The two proteins, P68 and P62, were antigenically related, since the antibody generated specifically against the 68-kDa band reacted with both the 68- and 62-kDa bands. Like rat testis SLIP1, purified boar sperm P68/62 bound to sulfogalactosylglycerolipid (SGG) and inhibited sperm-egg binding in a dose-dependent manner when added exogenously to sperm-egg coincubates. This inhibitory effect occurred at the level of the zona pellucida (ZP), and further studies showed that biotinylated boar sperm P68/62 bound to the ZP of unfertilized mouse eggs. Furthermore, biotinylated boar sperm P68/62 bound to isolated ZP of unfertilized eggs from other species, including pig, rat, cat, dog, and human, as well as to ZP of intact fertilized mouse eggs and preimplantation embryos of various developmental stages, although the degree of its binding to the ZP of intact eight-cell embryos, morulae, and blastocysts was much lower than that of fertilized eggs and two-cell embryos. These results suggest that P68/62 of capacitated sperm must act together with other sperm surface proteins/molecules that regulate zona binding specificity within homologous species and in unfertilized eggs. Together with our previous findings, we suggest that rather than being a true ZP receptor, sperm P68/62 may be involved in the initial step of sperm-ZP binding that is adhesive in nature.

Primary amenorrhoea: a retrospective study at Siriraj Hospital.

To determine the incidence of etiologic factors responsible for primary amenorrhoea in Siriraj Hospital on the basis of clinical examination and laboratory investigations. A retrospective study was performed from the records of patients who attended the Reproductive endocrine Clinic at Siriraj Hospital from 1 September 1992 to 31 August 1995. During the 3 years of the study period, there were 110 cases of primary amenorrhoea. One hundred and one cases were analyzed: nine cases were excluded because the patients lost follow-up before the final diagnosis could be concluded. The two most common etiologic factors were mullerian agenesis (39.65%) and gonadal dysgenesis (32.69%). Mean age of the patients when they first consulted the physicians was 22.45 +/- 6.06 years. Karyotyping was done on 28 of 32 cases of gonadal dysgenesis; 46,XX karyotype was found in 50 per cent and 45,XO in 14.29 per cent of analyzed cases. Clinical examination gave wrong diagnosis of absent uterus in 4 cases who were in the hypoestrogenic stage with hypoplastic uterus; ultrasonography and laparoscopy gave the wrong diagnosis in 1 case each in our report. These patients successfully menstruated after hormonal replacement therapy. The incidence of etiologic causes and cytogenetic study of primary amenorrhoea in our study is different from earlier reports. Racial and environmental differences may play a role in these differences. The facilities of diagnostic tools may also play a part. However, both clinical examination and many laboratory investigations have to be completed before final diagnosis of etiologic causes of primary amenorrhoea are elucidated. Diagnosis based on inadequate data can be misleading.