Lihui Hou

Polycystic ovary syndrome is associated with negatively variable impacts on domains of health-related quality of life: evidence from a meta-analysis

OBJECTIVE To systematically review the literature to identify the impact of polycystic ovary syndrome (PCOS) on specific health-related quality of life domains. DESIGN Meta-analysis. SETTING N/A. PATIENT(S) The outcomes of 423 patients and 285 controls from 5 articles that used the Short Form 36 (SF-36) questionnaire were used for meta-analysis. INTERVENTION(S) N/A. MAIN OUTCOME MEASURE(S) The SF-36 dimensions including physical function, physical role function, body pain, general health, vitality, social function, emotional role function, and mental health were evaluated. RESULT(S) Compared with controls, women with PCOS had lower scores in all SF-36 dimensions: physical function (mean differences [MD], -5.46; 95% confidence intervals [CI], -8.52, -2.41), physical role function (MD, -5.76; 95% CI, -8.49, -3.03), body pain (MD, -4.55; 95% CI, -7.99, -1.11), general health (MD, -11.34; 95% CI, -19.53, -3.15), vitality (MD, -15.14; 95% CI, -17.43, -12.84), social function (MD, -15.95, 95% CI, -18.57, -13.33), emotional role function (MD, -23.86; 95% CI, -27.51, -20.21), and mental health (MD, -13.83; 95% CI, -16.13, -11.53). CONCLUSION(S) The meta-analysis showed that women with PCOS score lower in each dimension of the SF-36, mostly in the emotional role function.

Maternal androgen excess reduces placental and fetal weights, increases placental steroidogenesis, and leads to long-term health effects in their female offspring

Here, we tested the hypothesis that excess maternal androgen in late pregnancy reduces placental and fetal growth, increases placental steroidogenesis, and adversely affects glucose and lipid metabolism in adult female offspring. Pregnant Wistar rats were randomly assigned to treatment with testosterone (daily injections of 5 mg of free testosterone from gestational days 16 to 19) or vehicle alone. In experiment 1, fetal and placental weights, circulating maternal testosterone, estradiol, and corticosterone levels, and placental protein expression and distribution of estrogen receptor-α and -β, androgen receptor, and 17β-hydroxysteroid dehydrogenase 2 were determined. In experiment 2, birth weights, postnatal growth rates, circulating testosterone, estradiol, and corticosterone levels, insulin sensitivity, adipocyte size, lipid profiles, and the presence of nonalcoholic fatty liver were assessed in female adult offspring. Treatment with testosterone reduced placental and fetal weights and increased placental expression of all four proteins. The offspring of testosterone-treated dams were born with intrauterine growth restriction; however, at 6 wk of age there was no difference in body weight between the offspring of testosterone- and control-treated rats. At 10-11 wk of age, the offspring of the testosterone-treated dams had less fat mass and smaller adipocyte size than those born to control rats and had no difference in insulin sensitivity. Circulating triglyceride levels were higher in the offspring of testosterone-treated dams, and they developed nonalcoholic fatty liver as adults. We demonstrate for the first time that prenatal testosterone exposure alters placental steroidogenesis and leads to dysregulation of lipid metabolism in their adult female offspring.

Insulin Resistance Directly Contributes to Androgenic Potential Within Ovarian Theca Cells

OBJECTIVE To investigate whether insulin resistance (IR) within theca cells may directly contribute to their hyperandrogenism, a heritable trait of polycystic ovary syndrome (PCOS). DESIGN In vitro cell model. SETTING University-affiliated laboratory. ANIMAL(S) Porcine ovaries. INTERVENTION(S) Ovarian theca cells from porcine follicles were isolated and cultured. Insulin resistance was induced in theca cells without (Con) or with dexamethasone (Dex); cells were further treated by troglitazone (Tro) and metformin (Met) in IR cells or by vehicle only in IR and Con cells. MAIN OUTCOME MEASURE(S) Medium glucose and T levels; reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot for insulin signal molecules and androgenic enzyme. RESULT(S) As compared with Con cells, Dex-treated cells had significantly lower [(3)H]-glucose uptake (565 +/- 58 cpm/10(6) vs. 1077 +/- 78 cpm/10(6)) but higher medium glucose levels (16.31 +/- 0.39 nmol/L vs. 10.62 +/- 1.02 nmol/L) and had approximately twofold T levels (0.82 +/- 0.20 microg/L vs. 0.38+/-0.08 microg/L). Troglitazone and Met significantly reduced the medium glucose and testosterone concentrations to levels comparable to those in Con cells. The RT-PCR and Western blot showed that the two sensitizers in different ways reversed the altered messenger RNA and protein expression of insulin receptor substrate-1, glucose transporter-4, peroxisome proliferator-activated receptor-gamma, and 17 alpha-hydroxylase in Dex-induced IR cells. CONCLUSION(S) Insulin resistance induced by Dex could directly exaggerate androgenic potential within theca cells, suggesting the possible involvement of this ovarian metabolic phenotype in PCOS hyperandrogenism.

Berberine reduces insulin resistance induced by dexamethasone in theca cells in vitro

Theca cells with dexamethasone-induced insulin resistance showed defective glucose uptake and excessive testosterone production, both of which were effectively antagonized by berberine. Therefore, insulin-resistant theca cells may contribute to the pathogenesis of hyperandrogenism in polycystic ovary syndrome.

Effect of Acupuncture and Clomiphene in Chinese Women With Polycystic Ovary Syndrome: A Randomized Clinical Trial

Importance Acupuncture is used to induce ovulation in some women with polycystic ovary syndrome, without supporting clinical evidence. Objective To assess whether active acupuncture, either alone or combined with clomiphene, increases the likelihood of live births among women with polycystic ovary syndrome. Design, Setting, and Participants A double-blind (clomiphene vs placebo), single-blind (active vs control acupuncture) factorial trial was conducted at 21 sites (27 hospitals) in mainland China between July 6, 2012, and November 18, 2014, with 10 months of pregnancy follow-up until October 7, 2015. Chinese women with polycystic ovary syndrome were randomized in a 1:1:1:1 ratio to 4 groups. Interventions Active or control acupuncture administered twice a week for 30 minutes per treatment and clomiphene or placebo administered for 5 days per cycle, for up to 4 cycles. The active acupuncture group received deep needle insertion with combined manual and low-frequency electrical stimulation; the control acupuncture group received superficial needle insertion, no manual stimulation, and mock electricity. Main Outcomes and Measures The primary outcome was live birth. Secondary outcomes included adverse events. Results Among the 1000 randomized women (mean [SD] age, 27.9 [3.3] years; mean [SD] body mass index, 24.2 [4.3]), 250 were randomized to each group; a total of 926 women (92.6%) completed the trial. Live births occurred in 69 of 235 women (29.4%) in the active acupuncture plus clomiphene group, 66 of 236 (28.0%) in the control acupuncture plus clomiphene group, 31 of 223 (13.9%) in the active acupuncture plus placebo group, and 39 of 232 (16.8%) in the control acupuncture plus placebo group. There was no significant interaction between active acupuncture and clomiphene (P = .39), so main effects were evaluated. The live birth rate was significantly higher in the women treated with clomiphene than with placebo (135 of 471 [28.7%] vs 70 of 455 [15.4%], respectively; difference, 13.3%; 95% CI, 8.0% to 18.5%) and not significantly different between women treated with active vs control acupuncture (100 of 458 [21.8%] vs 105 of 468 [22.4%], respectively; difference, −0.6%; 95% CI, −5.9% to 4.7%). Diarrhea and bruising were more common in patients receiving active acupuncture than control acupuncture (diarrhea: 25 of 500 [5.0%] vs 8 of 500 [1.6%], respectively; difference, 3.4%; 95% CI, 1.2% to 5.6%; bruising: 37 of 500 [7.4%] vs 9 of 500 [1.8%], respectively; difference, 5.6%; 95% CI, 3.0% to 8.2%). Conclusions and Relevance Among Chinese women with polycystic ovary syndrome, the use of acupuncture with or without clomiphene, compared with control acupuncture and placebo, did not increase live births. This finding does not support acupuncture as an infertility treatment in such women. Trial Registration clinicaltrials.gov Identifier: NCT01573858

Acupuncture and Clomiphene Citrate for Live Birth in Polycystic Ovary Syndrome: Study Design of a Randomized Controlled Trial

Acupuncture is an alternative therapy to induce ovulation in women with polycystic ovary syndrome (PCOS), but there is no study reporting the live birth rate following ovulation induction by acupuncture or its potential as an adjuvant treatment to clomiphene citrate (CC). We assess the efficacy of acupuncture with or without CC in achieving live births among 1000 PCOS women in Mainland China. This paper reports the methodology of an ongoing multicenter randomized controlled trial. The randomization scheme is coordinated through the central mechanism and stratified by the participating sites. Participants will be randomized into one of the four treatment arms: (A) true acupuncture and CC, (B) control acupuncture and CC, (C) true acupuncture and placebo CC, and (D) control acupuncture and placebo CC. To ensure the quality and integrity of the trial we have developed a unique multinational team of investigators and Data and Safety Monitoring Board. Up to the end of April 2013, 326 subjects were recruited. In conclusion, the success of this trial will allow us to evaluate the additional benefit of acupuncture beyond the first line medicine for fertility treatment in PCOS women in an unbiased manner.

Different phenotypes of polycystic ovary syndrome by Rotterdam criteria are differently steroidogenic but similarly insulin resistant

In traditional Chinese medicine, polycystic ovary syndrome (PCOS) is considered an anovulation disorder related to ovarian insulin resistance. The three phenotypes of PCOS, according to the Rotterdam criteria, are differently steroidogenic but similarly insulin resistant, suggesting a similar involvement of insulin resistance/hyperinsulinemia in different compartments of the PCOS ovary, namely, overactive theca and/or granulosa cells.

Cryptotanshinone reverses reproductive and metabolic disturbances in prenatally androgenized rats via regulation of ovarian signaling mechanisms and androgen synthesis

This trial explores 1) prenatally androgenized (PNA) rats as a model of polycystic ovary syndrome (PCOS) and 2) reproductive and metabolic effects of cryptotanshinone in PNA ovaries. On days 16-18 of pregnancy, 10 rats were injected with testosterone propionate (PNA mothers) and 10 with sesame oil (control mothers). At age 3 mo, 12 female offspring from each group were randomly assigned to receive saline and 12 cryptotanshinone treatment during 2 wk. Before treatment, compared with the 24 controls, the 24 PNA rats had 1) disrupted estrous cycles, 2) higher 17-hydroxyprogesterone (P = 0.030), androstenedione (P = 0.016), testosterone and insulin (P values = 0.000), and glucose (P = 0.047) levels, and 3) higher areas under the curve (AUC) for glucose (AUC-Glu, P = 0.025) and homeostatic model assessment for insulin resistance (HOMA-IR, P = 0.008). After treatment, compared with vehicle-treated PNA rats, cryptotanshinone-treated PNA rats had 1) improved estrous cycles (P = 0.045), 2) reduced 17-hydroxyprogesterone (P = 0.041), androstenedione (P = 0.038), testosterone (P = 0.003), glucose (P = 0.036), and insulin (P = 0.041) levels, and 3) lower AUC-Glu (P = 0.045) and HOMA-IR (P = 0.024). Western blot showed that cryptotanshinone reversed the altered protein expressions of insulin receptor substrate-1 and -2, phosphatidylinositol 3-kinase p85α, glucose transporter-4, ERK-1, and 17α-hydroxylase within PNA ovaries. We conclude that PNA model rats exhibit reproductive and metabolic phenotypes of human PCOS and that regulation of key molecules in insulin signaling and androgen synthesis within PNA ovaries may explain cryptotanshinones therapeutic effects.

The impairment of reproduction in db/db mice is not mediated by intraovarian defective leptin signaling

OBJECTIVE To demonstrate whether leptin modulates reproduction by a direct effect within the ovary. DESIGN Animal model. SETTING National Key Laboratory of Infertility. ANIMAL(S) Adult female db/db mice. INTERVENTION(S) Adult littermate wild-type (WT) and diabetic (db) leptin receptor (LR) mutant female mice were matched for the allograft of the ovary to construct new genotypic models, respectively. WT mouse received only one ovary from a WT or a db/db mouse (WT Ov-WT, WT Ov-db), and db/db mouse received one ovary from a WT or a db/db mouse (db Ov-WT, db Ov-db). WT and db/db mice received one ovary from a WT mouse and another ovary from a db/db mouse (WT Ov-WT/db, db Ov-WT/db) or received two ovaries all from a WT mouse (db Ov-WT/WT). MAIN OUTCOME MEASURE(S) Hormones, lipids, and reverse transcription polymerase chain reaction. RESULT(S) Both WT Ov-WT and WT Ov-db mice presented normal cycles, comparable serum E(2) and FSH levels, and ovarian expressions of the Star, Cyp17, and Cyp19 mRNA, even with different ovary genotypes. In WT Ov-WT/db with hMG stimulation, db ovaries with LR mutation expressed higher Star, Cyp17, Cyp19, Jak2, Stat3, and Pias3 mRNA than in the basal state, whereas WT ovaries with intact LR expressed higher Star, Cyp17, and Cyp19 but divergently lower Jak2, Stat3, and Pias3 levels. CONCLUSION(S) We confirmed that impairment of reproduction in intact db/db mice is not mediated by intraovary intact/defective leptin signaling even in face of a divergent modulation by gonadotropins.

Induction of insulin resistance by phosphatidylinositol-3-kinase inhibitor in porcine granulosa cells

Insulin resistance on porcine granulosa cells was induced by wortmannin, the phosphatidylinositol-3-kinase inhibitor, and insulin signaling key molecules were investigated including glut(4) and mitogen-activated protein kinase. Granulosa insulin resistance decreased glut(4) expression but increased mitogen-activated protein kinase, indicating the cross talk between the metabolic and mitogenic pathways of insulin signaling in the ovary.