Mei-Jou Chen

Relationship Between Androgen Levels and Blood Pressure in Young Women With Polycystic Ovary Syndrome

The role of testosterone on the development of hypertension is controversial, especially in women with polycystic ovary syndrome (PCOS) who have higher prevalence of obesity and insulin resistance than women without PCOS. Little is known about the association between serum testosterone level and blood pressure in young women with PCOS. In the 151 young Taiwanese women with PCOS enrolled in this cross-sectional study, we measured the body mass index, waist circumference, blood pressure, fasting glucose, fasting insulin, lipid profile, and hormone profiles. The free androgen index, total testosterone, and sex hormone-binding globulin, but not the level of dehydroepiandrosterone sulfate, significantly correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP). In multiple linear regression models adjusted for age, body mass index, and other anthropometric, metabolic, and hormonal variables, the level of serum free androgen index or total testosterone, but not the sex hormone-binding globulin, were independently related to SBP and DBP. The age- and body mass index–adjusted least-square mean of serum-free androgen index levels were significantly different between the highest quartile and other quartiles of the SBP and DBP levels. The high bioavailable testosterone levels (free androgen index: ≥19%) in women with PCOS increased the risk of elevated blood pressure (SBP ≥130 mm Hg and/or DBP ≥85 mm Hg) with an odds ratio of 3.817 (P=0.029; 95% CI: 1.14 to 12.74) after adjustment for age, anthropometric measures, and metabolic profiles. Our results suggest that the characteristic hyperandrogenemia in young women with PCOS was associated with an elevated SBP and DBP independent of age, insulin resistance, obesity, or dyslipidemia.

The relationship between anti-Müllerian hormone, androgen and insulin resistance on the number of antral follicles in women with polycystic ovary syndrome

BACKGROUND Anti-Müllerian hormone (AMH) is a biomarker that predicts the number of antral follicles and is involved in follicle arrest for women with polycystic ovary syndrome (PCOS). We investigated the association between the characteristic hyperandrogenemia, insulin resistance (IR), AMH, and the morphology and size of ovaries for women with PCOS. METHODS A total of 99 Taiwanese women with PCOS who were willing to undergo vaginal ultrasonography were enrolled in this cross-sectional study. RESULTS The number of antral follicles and the ovarian volume showed a significant correlation with AMH, total testosterone and the free androgen index, but not with age, body mass index (BMI) or the homeostasis model assessment of insulin resistance (HOMA-IR). AMH had a significant negative association with both BMI and HOMA-IR. Multiple stepwise regression analysis demonstrated that AMH, BMI and total testosterone were independently related to the number of antral follicles. AMH and total testosterone were the main determinants for ovarian volume in a stepwise regression model. CONCLUSIONS Our results suggest that not only the AMH level, but also obesity, IR and elevated androgen levels may relate to the development of the large size of antral follicle pool and ovarian volume in women with PCOS. Obesity and IR may enhance the follicular excess through the dysregulation of AMH or through the pathway of hyperandrogenemia. These findings might partly explain why adequate body weight management and improvement in IR can improve the ovulatory function for women with PCOS.

Optimal waiting period for subsequent fertility treatment after various hysteroscopic surgeries

OBJECTIVE To investigate the endometrial wound healing duration after a hysteroscopic surgery. DESIGN Prospective study. SETTING Tertiary university hospital. PATIENT(S) One hundred sixty-three women who underwent hysteroscopic surgeries for endometrial polyp (n = 37), submucous myoma (n = 65), uterine septum (n = 16), and intrauterine adhesion (IUA; n = 45). INTERVENTION(S) Postoperative office hysteroscopy was consecutively done until complete endometrial wound healing. If there was newly formed IUA occurring at the endometrial wounds, adhesiolysis was immediately done with the tip of the office hysteroscope. MAIN OUTCOME MEASURE(S) Office hysteroscopic inspection of endometrial wound healing and the presence of newly formed IUA. RESULT(S) Thirty-two of 37 women (86%) achieved a fully healed endometrium 1 month after polypectomy, a higher rate than those after myomectomy (18%), septal incision (19%), and adhesiolysis (67%). Postoperative office hysteroscopy revealed that 88% and 76% of the women had new IUA formation after septal incision and adhesiolysis, respectively, more than those after myomectomy (40%) and polypectomy (0%). Women with postoperative new IUA formation were less likely to achieve endometrial wound healing within 1 month compared with those who had no new IUA formation (31% vs. 61%). CONCLUSION(S) The duration of endometrial wound healing is different after various hysteroscopic surgeries. Postoperative new IUA formation is an important factor influencing endometrial wound healing.

Epithelioid trophoblastic tumor of the broad ligament: a case report and review of the literature.

We report an epithelioid trophoblastic tumor, a recently delineated type of gestational trophoblastic tumor (GTT), discovered in the right broad ligament of a 41-year-old woman. The patient had gestational trophoblastic disease and was treated with methotrexate regimen 15 times 10 years earlier. The yellowish, spongy tumor with tiny hemorrhage spots was located in the right broad ligament, adherent to the right ovary. Microscopically, the tumor was circumscribed, with a pushing border, and the epithelial-differentiated tumor cells grew in cords, nests, and sheets within which were aggregates of hyaline material and necrotic debris. Most tumor cells were mononuclear with distinct cell borders, eosinophilic cytoplasm, and had nuclei with occasional indistinct nucleoli. Scattered multinucleated cells consistent with syncytiotrophoblastic cells were also present. Immunohistochemical staining revealed strong diffuse reactivity for cytokeratins (AE1/AE3, CAM 5.2, CK18), and focal reactivity, mainly in syncytiotrophoblastic cells, for beta-human chorionic gonadotropin, human placental lactogen, and inhibin-alpha. The histologic and immunohistochemical features were characteristic of epithelioid trophoblastic tumor and helped to distinguish the tumor from other trophoblastic tumors and squamous cell carcinoma. Our unusual findings in this case included a high level of serum beta-human chorionic gonadotropin, an unusual tumor location, and a higher Ki-67 proliferative index of 47.2%.

The duration of pre-ovulatory serum progesterone elevation before hCG administration affects the outcome of IVF/ICSI cycles

STUDY QUESTION During controlled ovarian stimulation (COS), does the duration of premature serum progesterone (P) elevation before administration of hCG affect the outcomes of IVF/ICSI embryo transfer (-ET) cycles? SUMMARY ANSWER The duration of the premature serum P elevation is inversely related to the clinical pregnancy rate of IVF/ICSI-ET cycles. WHAT IS KNOWN AND WHAT THIS PAPER ADDS The majority of the previous studies only considered a single serum P measurement made on the day of hCG administration and the results of attempts to relate this to IVF/ICSI-ET outcomes were controversial. However, the effect of the duration of premature serum P elevation before the hCG administration on the outcomes of IVF/ICSI-ET cycles has not been studied well. Here we demonstrate that the duration of premature serum P elevation has a more significant inverse correlation than the absolute serum P concentration on the day of hCG administration with IVF/ICSI-ET outcomes. DESIGN It is a retrospective, single-centre cohort study. A total of 1784 IVF and/or ICSI-ET cycles were included from October 2005 to June 2011. PARTICIPANTS AND SETTING A total of 1784 patients underwent their IVF and/or ICSI-ET cycles in a university hospital IVF unit. The inclusion criteria include (i) age between 20 and 42 years and (ii) eligible indications for COS before IVF/ICSI. MAIN RESULTS AND THE ROLE OF CHANCE The duration of premature serum P elevation to >1 ng/ml is significantly inversely associated with the probability of clinical pregnancy (odds ratio = 0.773, 95% confidence interval: 0.660-0.891, P < 0.001), after adjustment for possible confounders with multivariate logistic regression analysis. However, the significance of inverse correlation between the absolute serum P concentration on the day of hCG administration with clinical pregnancy rate decreased after adjustment. BIAS, CONFOUNDING AND OTHER REASONS FOR CAUTION The cutoff value we chose to define premature serum P elevation (P > 1.0 ng/ml) might not be able to be applied to different immunoassay kits and study population. The retrospective nature of this study inevitably might be influenced by some selection bias. GENERALIZABILITY TO OTHER POPULATIONS Older patients (>42 years) are excluded from our study.

Hyperandrogenemia is independently associated with elevated alanine aminotransferase activity in young women with polycystic ovary syndrome.

CONTEXT Women with polycystic ovary syndrome (PCOS) have been implicated to have higher levels of alanine aminotransferase (ALT) because of the high prevalence of obesity. OBJECTIVE Our aim was to investigate the relationship between elevated ALT and aspartate aminotransferase (AST) activity and characteristic hyperandrogenism in women with PCOS. DESIGN AND SETTING We conducted a cross-sectional case-control study in a reproductive endocrinology clinic and voluntary annual medical health check-up program of the health management center in a tertiary medical center. PATIENTS A total of 279 women with PCOS and 279 age-frequency-matched healthy women were studied. INTERVENTIONS There were no interventions. MAIN OUTCOME MEASURES All subjects underwent anthropometric measurement, clinical history recorded by questionnaires, and biochemical tests after an overnight fast. RESULTS The prevalence of elevated ALT and AST levels was significantly higher in women with PCOS than healthy control subjects. Multivariate regression analysis for women revealed that the presence of PCOS was significantly associated with elevated ALT but not AST after adjustment for age, obesity, and dyslipidemia. The level of androgenicity represented by free androgen index in women with PCOS was significantly related to elevated ALT and AST levels in multivariate regression models. Women with PCOS who had the highest quartile of free androgen index level had the highest risk of elevated ALT level after adjustment for age, obesity, insulin resistance, and dyslipidemia. CONCLUSIONS The risk of elevated ALT level is significantly higher in women with PCOS than those without, independent of obesity. The elevated ALT levels in women with PCOS were associated with the increased androgen levels, independent of obesity, insulin resistance, and dyslipidemia.

High serum dehydroepiandrosterone sulfate is associated with phenotypic acne and a reduced risk of abdominal obesity in women with polycystic ovary syndrome

BACKGROUND Women with polycystic ovary syndrome (PCOS) are known to have high prevalence of acne and elevated androgen levels. The current study aims to determine if dehydroepiandrosterone sulfate (DHEAS) level is associated with the presence of acne and reduced risk of abdominal obesity in women with PCOS, after considering the concurrent high testosterone level and insulin resistance (IR). METHODS Three hundred and eighteen untreated consecutive Taiwanese women with PCOS were enrolled. Phenotypic hyperandrogenism was recorded, and BMI, waist circumference, waist-to-hip ratio, lipid profiles, fasting glucose and insulin levels and hormone profiles were measured. RESULTS Women with acne were younger, had higher serum DHEAS levels (6.01 ± 3.45 versus 4.87 ± 2.49 μmol/l, P = 0.002) and a lower BMI (P = 0.0006), but comparable serum testosterone levels, in comparison with women without acne. The aggravating effect of elevated DHEAS on the risk of acne (odds ratio = 2.15, 95% confidence interval: 1.25-3.68, P = 0.005 for DHEAS cut-off of 6.68 μmol/l) still exited after adjustment for age and BMI. The DHEAS level was positively correlated with the testosterone level, but inversely related to waist circumference, waist-to-hip ratio, BMI, IR index, low-density lipoprotein-cholesterol and triglycerides. Women with PCOS in the highest quartile of DHEAS had the lowest risk of abdominal obesity after adjustment for age, IR, dyslipidemia, testosterone and estradiol levels. CONCLUSIONS Our results demonstrated the high serum DHEAS in women with PCOS was associated with the presence of acne and a significantly reduced risk of abdominal obesity, independent of serum testosterone concentration and IR.

Impact of submucous myoma on the severity of anemia.

OBJECTIVE To analyze the impact of the diameter (myoma-φ) and the uterine cavity protruding proportion (protruding %) of the submucous myoma on serum hemoglobin (Hb) level. DESIGN Retrospective descriptive study. SETTING Tertiary university hospital. PATIENT(S) Two hundred fifty-nine women with a single submucous myoma. INTERVENTION(S) Transvaginal ultrasound examination and office hysteroscopy. MAIN OUTCOME MEASURE(S) Myoma-φ and protruding % were determined with transvaginal ultrasound scan and office hysteroscopy. Menorrhagic period (months) and serum Hb were recorded within 2 weeks of these examinations. RESULT(S) Serum Hb negatively correlated with myoma-φ, protruding %, and menorrhagic period. The negative association between serum Hb and protruding % was even more prominent after adjusting for myoma-φ. Multivariate regression analysis revealed that myoma-φ and protruding %, after adjusting for the confounding effect of menorrhagic period, maintained a strongly negative correlation with serum Hb level. When myoma-φ was <2 cm, however, the serum Hb levels were similar regardless of the protruding %. CONCLUSION(S) For women with a single submucous myoma, myoma-φ and protruding % can determine the serum Hb level significantly . As myoma-φ and protruding % increased, the serum Hb level decreased accordingly.

The relationship between follistatin and chronic low-grade inflammation in women with polycystic ovary syndrome

The circulating follistatin and high-sensitivity C-reactive protein (hsCRP) concentrations were significantly higher in 155 Taiwanese women with polycystic ovary syndrome (PCOS) than in 37 healthy controls. Follistatin and hsCRP levels in both the PCOS and control groups were significantly correlated with each other independent of obesity and insulin resistance.

Increased matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-1 secretion but unaffected invasiveness of endometrial stromal cells in adenomyosis

OBJECTIVE To investigate cell invasiveness and the production of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TIMP-2 in endometrial stromal cells (ESCs) of adenomyosis. DESIGN Prospective study. SETTING Tertiary university hospital. PATIENT(S) Twenty-one women with adenomyosis (study group) and 25 women without adenomyosis (control group). INTERVENTION(S) Endometrial stromal cells were purified from eutopic endometrium and were cultured in vitro. MAIN OUTCOME MEASURE(S) Matrigel invasion assay and measurement of MMP-2, MMP-9, TIMP-1, and TIMP-2 concentrations. RESULT(S) Endometrial stromal cell invasiveness of adenomyosis was not different from that of the control group (0.95 vs. 1, using the latter as the bench mark) in ESCs cultured alone. After the ESCs were cultured with IL-6, anti-IL-6, or GM6001 for 24 hours, the indices of cell invasion were not different between the two groups. MMP-2 (median 7.3 vs. 3.5 ng/mL) and TIMP-1 (median 12.1 vs. 3.9 ng/mL), but not MMP-9 and TIMP-2, secreted by ESCs in women with adenomyosis were much higher than those in women without adenomyosis. CONCLUSION(S) The formation of adenomyosis does not result from altered invasiveness of ESCs. The concomitant elevation of MMP-2 and TIMP-1 may partially justify why invasiveness was not increased, but other enzymes should also be considered.