Premature Ovarian Insufficiency Group Research Articles

The association between primary ovarian insufficiency and osteoporosis in the Canadian Longitudinal Study on Aging.

The objective of this study is to describe the association of premature ovarian insufficiency (POI) and early menopause on bone mineral density (BMD) and osteoporosis in a large cohort of women living in Canada. Cross-sectional baseline data from a deeply characterized cohort (female participants) of the Canadian Longitudinal Study on Aging was used. Additional bio-psycho-social characteristics that may influence bone health and the development of osteoporosis were explored. The mean age of women at the time of baseline assessment was 65 years (N = 12,339). When comparing women with POI to those with early and normal age of menopause, there was no difference in hip BMD between groups, but women in the POI group were more likely to have a higher rate of self-reported osteoporosis (21.9% vs 16.7%) and have used osteoporosis drugs (11.39% vs 7.63%). After adjustment, POI was found to increase the odds of osteoporosis, as diagnosed using BMD. Current cigarette smoking was found to influence this association. Protective factors included obesity and current hormone therapy use, but not the duration of hormone therapy use. Women in the POI group were more likely to be obese, have decreased physical activity, and were more likely to be current smokers. These results confirm findings from smaller cohorts illustrating that POI is associated with osteoporosis. Increasing understanding of the sequelae associated with an earlier loss of ovarian function will aid in targeting earlier screening and intervention strategies for women in Canada and abroad.

The relationship between vitamin E level and premature ovarian insufficiency.

The aim of this study is to investigate the role of vitamin E in the etiology of premature ovarian insufficiency (POI). This study included a total of 96 matched cases and controls, including the case group composed of 40 women with POI, and the control group composed of 56 women with normal menstrual cycles. Serum levels of vitamin E (also known as α-tocopherol), total cholesterol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and anti-Müllerian hormone (AMH) were determined. The relationship of α-tocopherol with FSH, LH and AMH levels in women were evaluated using regression models. We found a negative association of α-tocopherol levels with FSH and LH levels, and a positive correlation between a-tocopherol and AMH levels in the whole study population. In this study, α-tocopherol levels were significantly lower in women with POI than those in women with normal menstrual cycles. Vitamin E levels showed significantly statistical difference between the POI and control group (P < 0.001). Therefore, vitamin E is correlated to POI.

Impact of Hormonal Replacement Therapy on Bone Mineral Density in Premature Ovarian Insufficiency Patients.

: IntroductionPremature ovarian insufficiency (POI) is a type of hypergonadotropic hypogonadism caused by impaired ovarian function before the age of 40. Due to the hypoestrogenism, women with POI experience a variety of health complications, including an increased risk of bone mineral density loss and developing osteopenia and osteoporosis, which poses an important problem for public health. Purpose: The aim of this study was to evaluate and compare the values of bone mineral density (BMD), T-score and Z-score within the lumbar spine (L1-L4) using the dual energy X-ray absorptiometry method. The dual-energy X-ray absorptiometry (DXA) scans described in this original prospective article were performed at the time of POI diagnosis and after treatment with sequential hormone replacement therapy (HRT). Materials and methods: This study included 132 patients with a mean age of 31.86 ± 7.75 years who had been diagnosed with idiopathic POI. The control group consisted of 17 healthy women with regular menstrual cycles, with a mean age of 23.21 ± 5.86 years. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid-stimulating hormone (TSH), free thyroxine (fT4), insulin, and fasting serum glucose were measured. Lumbar spine (L1-L4) BMD was assessed by means of dual-energy X-ray absorptiometry. DXA scans were performed at the time of diagnosis and following treatment with sequential hormone replacement therapy (HRT) comprised of daily oral 2 mg 17-β-estradiol and 10 mg dydrogesterone. The mean time of observation was 3 ± 2 years. Results: Patients in the POI group presented with characteristic hypergonadotropic hypogonadism. They had a significantly decreased mean lumbar spine BMD when compared to healthy controls (1.088 ± 0.14 g/cm2) vs. 1.150 ± 0.30 g/cm2) (p = 0.04) as well as a decreased T-score (0.75 ± 1.167 vs. −0.144 ± 0.82) (p = 003). There was a significant increase in BMD (1.088 ± 0.14 vs. 1.109 ± 0.14; p < 0.001), T-score (−0.75 ± 1.17 vs. −0.59 ± 1.22; p < 0.001), and Z-score (−0.75 ± 1.12 vs. −0.49 ± 1.11; p < 0.001) after the implementation of HRT when compared to pre-treatment results. Conclusions: In conclusion, this study has demonstrated that patients with POI often have decreased bone mineral density and that the implementation of HRT has a significant and positive influence on bone mass. The implementation of full-dose HRT and monitoring of bone status is particularly important in these patients.

AMH assessment five or more years after an initially low AMH level

PurposeAnti-Müllerian hormone (AMH) is a biomarker reflecting ovarian reserve. A low AMH level before 39 years may be associated with a risk of menopause between 40 and 45 years. The risk of onset of premature ovarian insufficiency (POI) is, however, poorly documented. The objective of the study was to determine the prevalence of POI 5–10 years after an AMH assay below 8 pmol/L. MethodsWe included women aged younger than 36 years who underwent a complete workup for infertility between January 2008 and December 2013 at the University Hospital and had an AMH level less than 8 pmol/L. In 2018, 47 of these women were assessed clinically, and 21 of them agreed to undergo an ovarian reserve test. ResultsThe prevalence of POI after at least 5 years was 8/47, or 17 % [8 %–31 %]. The median time to diagnosis was 5.1 years [2.9–7.3]. There was a significant difference at T0 in the regularity of cycles between the two groups (p = 0.024) and in their baseline serum AMH level: 6.0 pmol/L in the non-POI group vs 4.2 pmol/L in the POI group (p = 0.002). ConclusionSerum AMH < 8 pmol/L before the age of 36 years appears to be a risk factor for POI. These women require regular follow-up, especially if their cycles are irregular.

Body composition in women with premature ovarian insufficiency using hormone therapy and the relation to cardiovascular risk markers: A case-control study.

To compare body composition between women with premature ovarian insufficiency (POI) using hormone therapy and controls with normal ovarian function, and to correlate body composition with cardiovascular risk markers in the POI group. A case-control study of 70 women with POI matched by age and body mass index with 70 controls. All were submitted to whole-body dual-energy X-ray absorptiometry (DXA) to analyse body composition. In the POI group, total cholesterol, HDL-cholesterol, LDL-cholesterol, VLDL-cholesterol, triglycerides, glucose, insulin, transaminases and C-reactive protein levels were measured, as well as the thickness of the carotid artery intima-media complex. Total mass, fat mass, lean mass (total, percentage and index) and the android/gynoid (A/G) ratio were similar in both groups; however, bone mineral content was lower (P<.001) in the POI group. Lean and fat mass indexes were 14.19±1.63 and 11.04±3.58, respectively, and the percentage of gynoid to android fat was higher (51.17±6.71% versus 47.74±9.19%; A/G ratio=0.93±0.15) in the POI group. In addition, the increase in total mass correlated positively with glucose and ALT levels and negatively with HDL-cholesterol. Increased A/G ratio was the measurement most frequently associated with cardiovascular risk markers. The body composition of women with POI using hormone therapy is similar to that of women with normal ovarian functionwith regard to lean and fat mass content and fat distribution. In women with POI, the higher the A/G ratio, the worse the cardiovascular risk markers.

Optimized platelet rich plasma releasate (O-rPRP) repairs galactosemia-induced ovarian follicular loss in rats by activating mTOR signaling and inhibiting apoptosis

Platelet rich plasma contains a collection of growth factors, and an optimal formulation, named O-rPRP, contains the highest possible concentration of growth factors. PurposeChallenging the healing power of O-rPRP in a high-galactose diet-induced premature ovarian insufficiency (POI) experimental rat model. MethodsRats were divided into four groups of ten rats each and treated for four week as follows; 1) the control group, fed with normal diet and received intraperitoneal (i.p.) injection of PBS once/week; 2) the POI group, fed with galactose diet (50%) and received PBS (i.p.) once/week; 3) the POI/O-rPRP group, fed a 50% galactose diet and received O-rPRP (i.p.) once/week; 4) the O-rPRP group (negative control), fed with a normal diet and received O-rPRP (i.p.) once/week. The levels of galactose, follicle stimulating hormone, 17 β-estradiol, anti-mullerian hormone and inhibin B were measured in serum samples. Western blotting and quantitative real-time PCR assays were employed to investigate the levels of miR-223, β1 integrin, p70S6k and MCL-1 in ovarian tissues. ResultsAfter O-rPRP treatment, β1 integrin expression was enhanced, and miR-223 expression was decreased. Unlike the untreated galactose group, in the group treated with O-rPRP, p70S6k and MCL-1 expression levels were increased, indicating that the mTOR growth signaling pathway was active and that apoptosis was inactive. After the introduction of O-rPRP, the number of follicles and the follicular maturation improved, which was consistent with the improvement of inhibin B levels and subsequent inhibition of FSH. ConclusionO-rPRP inhibited galactose-induced excessive atresia and provided an overall protective effect on the ovarian follicles.

Endothelial cell-specific-molecule-1 (endocan) levels in women with premature ovarian insufficiency: a prospective comparative study

There is an increased risk of cardiovascular disease in women with premature ovarian insufficiency (POI). A relationship between cardiovascular disease and endocan levels has been shown. Endocan is a marker that is prominent in many diseases caused by endothelial dysfunction and can be measured in the blood. POI is also associated with endothelial dysfunction. The causes of POI include chromosomal and genetic defects, autoimmune processes, chemotherapy, radiation, infections and surgery, but many are unidentified (idiopathic). This study aimed to evaluate serum endocan levels in women with idiopathic POI. The blood for analysis was obtained at the early follicular phase of the menstrual cycle and endocan levels were measured using a commercially available enzyme-linked immunosorbent assay kit. There were 38 patients with idiopathic POI in the study group and 39 healthy subjects in the control group. The median ages of the women were not significantly different between the groups 34 [7] years vs. 34 [7] years, respectively (p = .862). The median endocan level was not different in the POI and control group 769 [727] vs. 1077 [403] pg/mL, respectively (p = .603). Endocan is not associated with the cardiovascular diseases risk linked with endothelial dysfunction in idiopathic POI. Clinical trial number: NCT03932877 (Clinicaltrials.gov) IMPACT STATEMENT What is already known on this subject? There is an increased risk of cardiovascular disease in premature ovarian insufficiency (POI) due to the decreased level of oestrogen, which is linked with endothelial dysfunction. What do the results of this study add? This study showed that endocan is not associated with the cardiovascular disease risk linked with endothelial dysfunction in idiopathic POI. What are the implications of these findings for clinical practice and/or further research? A marker to be used to predict the risk of cardiovascular disease in patients with POI could facilitate in improving the quality of life of these patients. Moreover, advantageous and easy-to-measure markers are needed in larger sample studies to better understand the cardiovascular diseases risk in POI.

The significance of FMR1 CGG repeats in Chinese women with premature ovarian insufficiency and diminished ovarian reserve

BackgroundPrevious studies have shown that there is an association between FMR1 CGG repeats and ovarian dysfunction. The aim of this study is to assess the association between the number of CGG repeats in FMR1 in Chinese patients with premature ovarian insufficiency (POI) and diminished ovarian reserve (DOR).MethodsThis is a cross-sectional, case-control study, which enrolled 124 patients with POI, 57 patients with DOR and 111 normal menopausal controls. The demographic details along with other clinical data were recorded. The FMR1 CGG repeats were analyzed by polymerase chain reaction and microfluidic capillary electrophoresis.ResultsWe could detect two premutation carriers in the POI group (1.6%) and one in the control group (0.9%). No premutation carriers were identified in the DOR group. The frequency of FMR1 premutations was not different between POI or DOR and controls. The most common CGG repeat was 29 and 30, and the repeat length for allele 2 had a secondary peak around 36–39 repeats. The CGG repeats were divided into groups of five consecutive values, and the distribution of allele 1 in the POI group was different from that in the control group (P < 0.001). No statistically significant differences were found for allele 1 between DOR group vs. controls, and for allele 2 between three groups (P > 0.05).ConclusionsThe study shows that the frequency of FMR1 premutations is relatively low (1.6%) in Chinese women with POI. The distribution of allele 1 CGG repeat in patients with POI showed difference from that in healthy women.

Intra-ovarian injection of platelet-rich plasma into ovarian tissue promoted rejuvenation in the rat model of premature ovarian insufficiency and restored ovulation rate via angiogenesis modulation

Premature Ovarian Insufficiency (POI) is viewed as a type of infertility in which the menopausal status occurs before the physiological age. Several therapeutic strategies have been introduced in clinic for POI treatment, although the outputs are not fully convincing. Platelet-rich plasma (PRP) is a unique blood product widely applied in regenerative medicine, which is based on the releasing of the growth factors present in platelets α-granules. In the current investigation, we examined the effectiveness of PRP as a therapeutic alternative for POI animals. POI in Wistar albino rats was induced by daily intraperitoneal (IP) administration of gonadotoxic chemical agent, 4-vinylcyclohexene dioxide (VCD) (160 mg/ kg) for 15 consecutive days. After POI induction, the PRP solution was directly injected intra-ovarian in two concentrations via a surgical intervention. Every two weeks post-injection, pathological changes were monitored in the ovaries using Hematoxylin-Eosin staining method, until eight weeks. Follicle Stimulating Hormone (FSH) content in serum was measured, together with the expression of the angiogenic-related transcripts ANGPT2 and KDR by real-time qPCR. Furthermore the fertility status of the treated rats was evaluated by mating trials. Histopathological examination revealed successful POI induction via the depletion of morphologically normal follicles in rats following VCD treatment compared to the control rats. The injection of PRP at two concentrations reduced the number and extent of the follicular atresia and inflammatory responses (p < 0.05). The expression of both ANGPT2 and KDR transcripts were significantly increased in POI rats due to enhanced inflammation, while these values were modulated after PRP administration (p < 0.05) compared to POI rats. FSH showed a decreased trend in concentration eight weeks after PRP treatment, but not statistically significant (p > 0.05). Nevertheless, a clear improvement in litter counts was found in POI rats receiving PRP compared to the non-treated POI group, being able to consider PRP as a facile, quick, accessible, safe and relatively cheap alternative therapeutic strategy to revert POI-related pathologies.

Exosomal miRNA-320a Is Released from hAMSCs and Regulates SIRT4 to Prevent Reactive Oxygen Species Generation in POI

Human amniotic mesenchymal stem cells (hAMSCs) were previously shown to effectively rescue ovarian function in a premature ovarian insufficiency (POI) mouse model. The therapeutic mechanism of hAMSC-derived exosomes (hAMSC-Exos) is not fully understood. In this study, the therapeutic mechanism involved in exosomal microRNA-320a (miR-320a) and Sirtuin 4 (SIRT4) was investigated in POI mouse ovaries oocytes and human granulosa cells (hGCs) by fluorescence-activated cell sorting (FACS), hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence experiments. hAMSC-Exos improved proliferation, inhibited apoptosis, and decreased the expression of SIRT4 and relative genes in POI hGCs and ovaries. hAMSC-Exos elevated ovarian function and prohibited SIRT4 expression in oogenesis. The therapeutic effects were attenuated when miR-320a was knocked down. hAMSC-Exos decreased the ROS levels in POI hGCs and oocytes and improved ovarian weight and litter size, except for the Exosanti-miR-320a/POI group. Finally, hAMSC-Exos reduced the SIRT4 and ROS levels in POI ovaries and hGCs. The downstream protein expression (ANT2, AMP-dependent kinase [AMPK], and L-OPA1) was downregulated in the hGCs-SIRT4KD group but disappeared in the Exosanti-miR-320a/POI group. Our study is the first to illustrate the therapeutic potential of hAMSC-Exos in POI. Exosomal miR-320 plays a key role in the hAMSC-Exos-mediated effects on ovarian function via SIRT4 signaling.

Pelvic floor disorders in women with premature ovarian insufficiency: a cross-sectional study.

This study aimed to investigate the prevalence of self-reported main pelvic floor disorders (PFD) (urinary incontinence [UI], pelvic organ prolapse [POP], and fecal incontinence [FI]) and its associated factors in women with premature ovarian insufficiency (POI) and a control group. This was a cross-sectional study wherein two groups were interviewed from August, 2017 to November, 2018-women with POI (n = 150) and a control group matched for age and body weight (n = 150). Sociodemographic variables and two questionnaires validated in Brazilian Portuguese language for PFD (Kings Health Questionnaire [KHQ] and Pelvic Floor Distress Inventory-20 [PFDI-20]) were used. Laycock's power, endurance, repetitions, fast contractions, every contraction timed (PERFECT) scale for pelvic floor muscle assessment was used in both groups. The prevalence of self-reported UI was 27.33% and 37.33% for POI and control groups (P > 0.05), respectively. There was no perceived difference regarding the prevalence of POP (9.33% POI group vs 8% control group; P = 0.682) and FI (8% POI vs 4% control group; P = 0.145). The P (power) (P = 0.46), E (endurance) (P = 0.91), R (repetitions) (P = 0.88), and F (fast contractions) (P = 0.19) values were statistically similar in both the groups. Multivariate analysis (n = 141) showed that higher weight (odds ratio [OR] 1.047 [1.018-1.076]; P < 0.001) and gravidity rates (OR 1.627 [1.169-2.266]; P < 0.01) were risk factors for UI and higher weight (OR 1.046 [1.010-1.084]; P = 0.01), and presence of comorbidities (OR 8.75 [1.07-71.44]; P < 0.01) were risk factors for POP in the POI group; there was no variable that was associated with FI. Women with POI did not have significant differences when compared with the control group regarding the prevalence of PFD and pelvic floor muscle assessment. Having higher weight and gravidity rates were associated with self-reported UI, while the presence of comorbidities and higher weight were risk factors for POP in the POI group. : Video Summary:http://links.lww.com/MENO/A555.

Extracellular Vesicles Derived from Mesenchymal Stem Cells Recover Fertility of Premature Ovarian Insufficiency Mice and the Effects on their Offspring

It has been reported that extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HUCMSCs) can promote the proliferative and secretive functions of granulosa cells. In vivo study further demonstrated that EVs derived from HUCMSCs can not only promote the angiogenesis of ovarian tissue but also restore the function of an ovary of chemically induced premature ovarian insufficiency (POI) mice. However, no study investigates the effects of HUCMSCs derived EVs on fertility recovery of POI mice and evaluating their offspring. This study investigates the effects of HUCMSCs derived EVs on fertility recovery and the cognitive function of their offspring. A POI model was established by intraperitoneal injection of cyclophosphamide (CTX) and busulfan (BUS), and randomly divided into EVs-transplantation group (a single injection of 150 µg EVs proteins which suspended in 0.1 ml phosphate buffer saline [PBS] via tail vein), POI group (a single injection of 0.1 ml PBS via tail vein), and normal control group (a single injection of 0.1 ml PBS via tail vein without intraperitoneal injection of CTX and BUS). After EVs treatment, not only the ovarian function of POI mice recovered but also the fertility increased with less time to get pregnant, evaluating by in vitro fertilization and mating test. Cognitive behaviors of the offspring were similar among the three groups through the Y-maze test and novel object recognition task. An anti-apoptotic effect was identified through immunohistochemistry, real-time polymerase chain reaction and western blot. These findings indicate that HUCMSCs derived EVs can improve the fertility of POI mice without adverse effects on the cognitive behavior of their offspring, highlighting the potential value of EVs to be a cell-free therapy for patients suffering from POI.

LncRNA PVT1 Overexpression Improves Premature Ovarian Insufficiency by Inhibiting Granulosa Cell Apoptosis

Background: Long noncoding RNA PVT1 (plasmacytoma variant translocation 1) is aberrantly expressed in a variety of cancers. However, whether PVT1 is aberrantly expressed in granulosa cells from premature ovarian insufficiency (POI) patients and the role of PVT1 in POI is largely unknown. Methods: The interaction between PVT1 and Foxo3a was confirmed by RNA pull-down and RNA immunoprecipitation (RIP) assays. Methylation level in PVT1 promoter region was detected by methylation-specific PCR. The subcellular location of PVT1 was detected by FISH assay. Granulosa cell apoptosis was detected using flow cytometry. The effect of PVT1 on the transcriptional activity of Foxo3a was detected by luciferase reporter assay. Results: PVT1 was down-regulated in ovarian tissues of POI group than control group, which was regulated by high methylation level. PVT1 was mainly localized in cytoplasm of granulosa cells. In addition, we determined PVT1 interacted with Foxo3a, down-regulation of PVT1 inhibited Foxo3a phosphorylation, resulting in the suppression of Foxo3a degradation and the increase of Foxo3a transcriptional activity. Moreover, down-regulation of PVT1 promoted granulosa cell apoptosis through Foxo3a. Finally, in vivo experiment showed that overexpression of PVT1 restored ovarian function in POI mice. Conclusion: Down-regulation of PVT1 inhibits Foxo3a phosphorylation that suppresses its degradation and activates the transcriptional activity of Foxo3a, thereby promoting granulosa cell apoptosis in POI. Funding Statement: This study was supported by International (Regional) Cooperation and Exchange (ICE) Projects of the National Natural Science Foundation of China (NSFC) (Grant No. 81820108016), Clinical Medical Research Fund of Chinese Medical Association-Reproductive Medicine Research and Development Projects for Youth Grant: Application study of human fetal primordial germ cells to oocyte differentiation and development in vitro (Grant No. 17020210690), and Henan Provincial Science and Technology Project: Study on the mechanism of meiosis initiation induced by human primordial germ cells to oocytes in vitro (Grant No. 182102310139). Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Clinical Research Ethics Committee of the first affiliated hospital of Zhengzhou University (Ethical review number: 2019-KY-158). Written informed consents were obtained from all the patients involved. The animal experiment was approved by the Ethics Committee of the first affiliated hospital of Zhengzhou University.

Novel FSHR mutations in Han Chinese women with sporadic premature ovarian insufficiency

Premature ovarian insufficiency (POI) is characterized by amenorrhea and elevated levels of follicle-stimulating hormone (FSH, usually > 25 IU/L) before 40 years of age. To identify the relationship between FSHR mutations and sporadic POI patients of Han Chinese descent, we performed Sanger sequencing of FSHR gene in 192 sporadic POI patients and 192 matched controls of Han Chinese descent. Two heterozygous missense variants, c.793A > G (p.M265V) and c.1789C > A (p.L597I), were identified exclusively in POI patients. Functional studies showed that both mutants were expressed on the cell surface, while p.L597I showed decreased membrane localization compared with wild-type FSHR. Moreover, FSH-induced cAMP production and ERK1/2 phosphorylation were reduced in the cells transfected with p.L597I mutant, but not in the cells transfected with p.M265V mutant. In addition, two single-nucleotide polymorphisms (SNPs), rs1394205 (c.-29G > A) and rs140106399 (c.*111 T > C), were identified in both POI group and control group with significantly different genotypic and allelic distributions. These results indicated that dysfunctional FSHR due to mutation or SNPs might explain a fraction of sporadic POI cases in Han Chinese population.

Cardiovascular risk and the possibility of its correction in women with premature ovarian insufficiency

Since recently, the association of premature ovarian insufficiency (POI) with an increased risk of mortality and morbidity caused by cardiovascular diseases (CVD) has been extensively discussed in the context of early detection and prevention of CVD in these patients.Aim: to evaluate the relative cardiovascular risk (CV risk) before and after hormone replacement therapy (HRT) in women with POI.Materials and methods. The study included 170 women aged from 18 to 40; among them, 85 women with POI and 85 women with regular periods. We evaluated the usual CV risk factors: smoking habits, arterial blood pressure, total cholesterol (TC), low-density lipoproteins (LDL), high-density lipoproteins; in addition, we determined apolipoprotein B (Apo B), high-sensitivity C-reactive protein (hs-CRP), uric acid, and endotelin-1, as well as the functional markers: the right and left carotid intima-media thickness (CIMT) and the brachial artery flow-mediated dilatation (FMD). The CV risk was calculated using the relative risk SCORE scale before and after HRT lasted for 12 months.Results. In the POI group, there were 3.8 times more women with a moderate CV risk (per the SCORE scale), whereas in the POI-free group, women with a low CV risk dominated. In addition, the levels of CV risk markers were 4-fold higher in patients with POI (high levels of Apo B, hs-CRP and uric acid, increased CIMT bilaterally, decreased FMD in the brachial artery). Cyclic HRT during 12 months contributed to the lipid profile normalization, decrease in TC, LDL and FMD in the brachial artery as well as to the decrease of relative CV risk in general.Conclusion. The estrogen deficiency in patients with POI is an independent factor in the increased relative risk of CVD. The HRT has anti-atherogenic, antiinflammatory, and angioprotective effects, regulates the production of endothelium-dependent factors of vasoconstriction and vasodilation, leading to a reduction in the relative risk of CVD in general.

Prevalence of Stress Urinary Incontinence in Women with Premature Ovarian Insufficiency.

Background: To determine the prevalence of stress urinary incontinence (SUI) and associated factors in women with premature ovarian insufficiency (POI). Materials and Methods: The study included 149 patients with POI and 303 control women without POI. Age, body mass index (BMI), gestational history, time since onset of POI, and status of hormone therapy (HT) for POI were recorded. Results: There was no statistical difference in the mean age, BMI, and parity between the two groups. The prevalence of SUI in the POI group tended to be higher than that in the control group (20.9%, 30/149 vs. 16.2%, 49/303), although not significantly (p = 0.297). About 41.6% (62/149) of patients with POI received HT. Patients with POI and SUI were older (p = 0.018) and had higher BMI (p = 0.007) than women with POI without SUI (p = 0.007). Compared to nulliparas, primiparas were more likely to have SUI (p = 0.046). However, SUI developed irrespective of time since onset of oligomenorrhea/amenorrhea or HT use. Furthermore, regression analysis showed that the prevalence of SUI was higher in women 30-39 years of age (odds ratio [OR] = 3.27, p = 0.002) and older than 40 years (OR = 7.78, p = 0.001). Primiparas (OR = 2.89, p = 0.001) and vaginal delivery (OR = 2.58, p = 0.023) were associated with SUI. Conclusions: The prevalence of SUI was fairly high among patients with POI, and age, parity, and vaginal delivery were the main risk factors. However, duration of POI and HT use had no effect on SUI. Increasing awareness of the importance of urinary system health in this population will improve the quality of life for these women.

Metabolic Profile of Patients with Premature Ovarian Insufficiency.

Premature ovarian insufficiency (POI) is hypogonadism associated with amenorrhea, increased levels of gonadotropins, and hypoestrogenism. Deficiency of estrogens may contribute to higher risk of cardiovascular diseases and death. POI patients present several risk factors for the development of cardiovascular diseases (CVD): endothelial dysfunction, abnormal lipid profile, insulin resistance, and insulin action disturbances. Therefore, patients present a higher risk of developing metabolic syndrome. Materials and methods: Follicle stimulating hormone (FSH), luteinizing hormone (LH), 17β-estradiol (E2), prolactin (PRL), testosterone (T), dehydroepiandrosterone sulfate (DHEA-S), thyroid stimulating hormone (TSH), thyroxine (fT4), fasting serum glucose and insulin concentrations, homeostatic model for insulin resistance (HOMA-IR), and lipid profiles were assessed in 56 women (mean age: 30.7 ± 6.9) suffering from POI diagnosed according to European Society of Human Reproduction and Embryology (ESHRE) criteria and 68 healthy age-and-weight matched women (mean age: 27.3 ± 4.5). Results: After regression analysis with BMI and age correction, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) serum concentrations were found to be significantly higher in the POI group, when compared to healthy subjects, whilst triglycerides, glucose, insulin serum concentrations, HOMA-IR, as well as systolic (SBP) and diastolic blood pressure (DBP) did not differ significantly between both groups. A significant positive correlation was identified between TC and LDL-C levels, regardless of BMI and age, whilst SBP correlated only with serum glucose concentration. Additionally, FSH correlated positively with fasting serum glucose concentration after BMI and age correction. Conclusions: Certain metabolic parameters appeared to correlate with POI and these correlations persisted after correction for BMI and age. More research is required to determine the influence of absent ovulatory function on metabolic profiles in POI women. This information may additionally help in early identification of CVD risk factors in those patients.

The role of ADAMTS4 and ADAMTS9 in cardiovascular disease in premature ovarian insufficiency and idiopathic hypogonadotropic hypogonadism

We aimed to determine the relation of a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4), and a disintegrin and metalloproteinase with thrombospondin motifs-9 (ADAMTS9) with cardiovascular disease (CVD) risk, in ovarian dysfunction patients with premature ovarian insufficiency (POI), and idiopathic hypogonadotropic hypogonadism (IHH). 43 IHH and 44 POI patients were enrolled to this case-control study. Serum hormonal parameters, lipid profiles, ADAMTS4 and ADAMTS9 levels were measured. Lipid accumulation product (LAP) index, visceral adiposity index (VAI), and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The patients with at least two out of the four following criteria were accepted to have increased CVD risk; waist-to-hip ratio (WHR) ≥ 0.8, waist circumference (WC) ≥ 79cm, triglycerides (TG) ≥ 150mg/dL, high-density lipoprotein cholesterol (HDL-C) < 50mg/dL. Serum ADAMTS4 and ADAMTS9 levels were measured by enzyme-linked immunosorbent assay (ELISA). ADAMTS4 and ADAMTS9 levels were significantly higher in the IHH group than the POI group (p = 0.002, and p = 0.013, respectively). IHH group had significantly higher levels of insulin, HOMA-IR index, and LAP index (p = 0.006, p = 0.005, and p = 0.013, respectively). The mean age of patients in the IHH group (23.60 ± 5.64years) was significantly lower than the POI group (31.05 ± 6.03years), (p < 0.001). Odds ratios (OR) were 1.236 (95% CI 1.055-1.447) and 1.002 (95% CI 1.000-1.004) for LAP index and ADAMTS4, respectively, in the IHH group. These two parameters found to have high predictivity for CVD risk in the IHH group (p = 0.009 and p = 0.028, respectively). The lower levels of ADAMTS4 in the POI group, when compared with the IHH patients pointed out that even limited hormone secretion and ovulation in the POI group, may have protective effect on cardiovascular system. The higher levels of ADAMTS4 and LAP index in the IHH group demonstrated the increased risk of these patients for CVD.

Influence of Sexual Function on the Social Relations and Quality of Life of Women with Premature Ovarian Insufficiency.

To evaluate the impact of sexual function (SF) in the quality of life (QoL) of women with premature ovarian insufficiency (POI). Case-control study in which 80 women with POI were evaluated using estrogen plus progestogen therapy, compared with 80 women matched by age (±2 years) and presenting preserved gonadal function. Sexual function was evaluated using the Female Sexual Function Index (FSFI), and the QoL was evaluated using the World Health Organization's (WHO) QoL assessment instrument (WHOQoL-BREF). The mean age of the women with POI and of the control group was 38.4 ± 7.3 years and 38.1 ± 7.3 years respectively. The QoL, was worse among the POI group, and there were significant differences in the physical (63.4 ± 17.4 and 72.7 ± 15.2 respectively, p = 0.0004) and psychological (63.2 ± 14.6 and 69.3 ± 13.9 respectively, p = 0.0075) domains among this group when compared with the control group. Women with POI presented significantly lower arousal, lubrication, orgasm and satisfaction, more dyspareunia and a worse FSFI scores when compared with the control group. All aspects of SF correlate directly with the worsening of the QoL regarding social relationships. Women with POI showed worse QoL and SF than the control group. The psychological aspects (desire, excitement, orgasm and sexual satisfaction) of SF had greater influence on the parameters of the QoL, while the physical aspects (pain and lubrication) had a low impact on the QoL. The poor SF in women with POI is directly correlated with a worsening across multiple domains of the QoL; however, the negative impact is particularly important in the social domain. These results suggest that the improvement in sexuality can improve the social interactions of women with POI.

How polymorphic markers contribute to genetic diseases in different populations? The study of inhibin A for premature ovarian insufficiency.

ABSTRACTObjective To verify the incidence of the G679A mutation in exon 2 of the gene inhibin alpha (INHA), in women with secondary amenorrhea and diagnosis of premature ovarian insufficiency, and in controls.Methods A 5mL sample of peripheral blood was collected from all study participants in an EDTA tube and was used for DNA extraction. For the patient group, 5mL of blood were also collected in a tube containing heparin for karyotype, and 5mL were collected in a dry tube for follicle stimulant hormone dosage. All patient and control samples were initially submitted to analysis of the G679A variant in exon 2 of the INHA gene by PCR-RFLP technique. Samples from patients with premature ovarian insufficiency after PCR-RFLP were submitted to Sanger sequencing of the encoding exons 2 and 3. Sequencing was performed on ABI 3500 GeneticAnalyzer equipment and the results were evaluated by SeqA and Variant Reporter software.Results Samples of 70 women with premature ovarian insufficiency and 97 fertile controls were evaluated. The G769A variant was found in only one patient in the Premature Ovarian Insufficiency Group and in no control, and it appears to be rare in Brazilian patients with premature ovarian insufficiency. This polymorphism was previously associated to premature ovarian insufficiency in several populations worldwide.Conclusion There is genetic heterogeneity regarding the INHA gene in different populations, and among the causes of premature ovarian insufficiency.