Female sexual dysfunctions: an overview on the available therapeutic interventions.

INTRODUCTION: There are different types of female sexual dysfunctions (FSDs), and FSD in general has a high prevalence worldwide. Studies of FSD should consider it as a multifactorial disorder that has biological, psychological, environmental, and relational aspects. In this review we discuss the available therapeutic interventions for FSD. EVIDENCE ACQUISITION: For the current narrative review the PubMed database was searched to identify all publications up to 30 March 2021 that were systematic reviews and meta-analyses which examined therapeutic interventions for FSDs based on the diagnostic classifications of ICD-10 and ICD-11. EVIDENCE SYNTHESIS: Thirty systematic reviews and meta-analyses were included in this review. Hormone therapy (HT) and testosterone are effective to improve sexual desire in menopausal women. In these women HT and ospemiphene may improve pain during intercourse. Flibanserin may improve sexual desire and may reduce desire-related distress in premenopausal women. Bremelanotide is effective to improve desire, arousal, and orgasm scores. Evidence are still limited on the efficacy of psychoactive drugs, phosphodiesterase type 5 (PDE5), oxytocin, herbal drugs, and tibolone to treat FSDs. Psychological interventions such as cognitive-behavior therapy, mindfulness training, sensate focus, bibliotherapy are effective for the management of several different FSDs. CONCLUSIONS: The management of FSDs may require multidisciplinary and interdisciplinary approaches. Pharmacological and nonpharmacological interventions appears to have potential as a treatment for FSDs, but there are currently no gold standards regarding recommended treatment modalities, and the duration, frequency, and intensity of therapy sessions.

Telomere Length and Telomerase Activity in Immature Oocytes and Cumulus Cells of Women with Polycystic Ovary Syndrome.

Metaphase II oocytes (MII) from polycystic ovary syndrome (PCOS) frequently have impaired oocyte competence. Since telomere maintenance is important for folliculogenesis, oocyte maturation, and early embryonic development, we sought to verify the implications of PCOS on telomere length and telomerase activity in immature oocytes and cumulus cells. 43 PCOS and 67 control women were included, and anthropometric, biochemical, and hormonal characteristics were evaluated. The telomere length in germinal vesicle stage (GV) and in metaphase I (MI) oocytes, as well as in the cumulus cells of immature (CCI) and mature oocytes (CCM), and in leukocytes was measured by qPCR. The telomerase activity in reproductive cells was evaluated by the TRAPeze® XL Kit. The body mass index (p = 0.001), LH (p = 0.015), estradiol (p = 0.004), insulin (p = 0.002), testosterone (p < 0.0001), androstenedione (p = 0.001), free androgen index (p < 0.0001), and c-reactive protein (p = 0.003) were greater, while the FSH (p = 0.0002) was lower in the PCOS group. The telomere length in the CCI (p = 0.649) and CCM (p = 0.378) did not differ between the PCOS and the control groups. On the other hand, telomerase activity in the CCI (p = 0.003) and CCM (p = 0.022) was higher in the PCOS group. In the leukocyte's cells, the telomere length was reduced in the PCOS group (p = 0.025). In the GV and MI oocytes, no differences were observed in telomere length and telomerase activity between the groups. We showed that telomere length is not altered in reproductive cells from PCOS. However, higher telomerase activity in the CCI and CCM may be required for telomere length maintenance.

Effects of Progressive Resistance Training on Obesity Indices in Polycystic Ovary Syndrome and the Relationship With Telomere Length.

BACKGROUND: Physical activity is prescribed as a component of primary management for polycystic ovary syndrome (PCOS). This nonrandomized, therapeutic, open, single-arm study investigated the effects of progressive resistance training (PRT) on obesity indices in women with PCOS, and the relationship between obesity indices and telomere content. METHODS: A total of 45 women with PCOS and 52 with non-PCOS (controls), aged 18 to 37 years, with body mass indexes of 18 to 39.9 kg/m2, performed three 1-hour sessions of PRT per week, for 16 weeks. Before and after PRT, measures included anthropometric indices and regions of interest of fat mass distribution, quantified by dual-energy X-ray absorptiometry, metabolic and hormonal parameters, and telomere content. The general linear mixed models were used to determine the effects of PRT. RESULTS: PRT did reduce the waist-to-height ratio, waist circumference, and the index of conicity among PCOS (P < .01). However, PRT did not influence regions of interest, body mass index, and WHR. After PRT, the telomere content was associated with regions of interest and anthropometric indices in whole group independent of PCOS (P < .05). CONCLUSION: Resistance exercise improves obesity indices in PCOS, independent of changes in body weight, and the relationship between telomeres and obesity parameters in PCOS remain to be fully clarified.

Skewed X-chromosome inactivation and shorter telomeres associate with idiopathic premature ovarian insufficiency.

OBJECTIVE: To analyze whether telomere length, X-chromosome inactivation (XCI), and androgen receptor (AR) GAG polymorphism are related to idiopathic premature ovarian insufficiency (POI). DESIGN: Case-control study. SETTING: University hospital. PATIENT(S): A total of 121 women, including 46 nonsyndromic POI and 75 controls. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age, weight, height, body mass index (BMI), systolic and diastolic arterial pressure, E2, androstenedione, T, and C-reactive protein were assessed. Telomere length was estimated by quantitative real-time polymerase chain reaction, XCI was measured using the Human Androgen Receptor and X-linked retinitis pigmentosa 2 (RP2) methylation assays. AR and FMR1 polymorphism was assessed by quantitative fluorescent polymerase chain reaction and sequencing. RESULT(S): Premature ovarian insufficiency women had a higher mean age, weighed less, and exhibited lower C-reactive protein, E2, and androstenedione levels. The AR polymorphism did not differ between the groups. Four patients had premutation (55-200 CGG repeats), and none displayed a full mutation in the FMR1 gene. However, patients with POI showed shorter telomere length and higher frequency of skewed XCI. Extreme skewing (≥90%) was observed in 15% of women with POI, and shorter telomeres correlated with XCI skewing in both groups. CONCLUSION(S): Skewed XCI and shortened telomere length were associated with idiopathic POI, despite no alterations in the AR and FMR1 genes. Additionally, there is a tendency for women with short telomeres to exhibit skewed XCI.

Polycystic Ovary Syndrome Presents Higher Sympathetic Cardiac Autonomic Modulation that is not altered by Strength Training.

Polycystic ovary syndrome (PCOS) may present important comorbidities, such as cardiovascular and metabolic diseases, which are often preceded by changes in cardiac autonomic modulation. Different types of physical exercises are frequently indicated for the prevention and treatment of PCOS. However, little is known about the effects of strength training on the metabolic, hormonal, and cardiac autonomic parameters. Therefore, our aim was to investigate the effects of strength training on the autonomic modulation of heart rate variability (HRV) and its relation to endocrine-metabolic parameters in women with PCOS. Fifty-three women were divided into two groups: CONTROL (n=26) and PCOS (n=27). The strength training lasted 4 months, which was divided into mesocycles of 4 weeks each. The training load started with 70% of one repetition maximum (1RM). Blood samples were collected before and after intervention for analysis of fasting insulin and glucose, HOMA-IR, testosterone, androstenedione and testosterone/androstenedione (T/A) ratio. Spectral analysis of HRV was performed to assess cardiac autonomic modulation indexes. The PCOS group presented higher insulin and testosterone levels, T/A ratio, along with increased sympathetic cardiac autonomic modulation before intervention. The training protocol used did not cause any change of endocrine-metabolic parameters in the CONTROL group. Interestingly, in the PCOS group, reduced testosterone levels and T/A ratio. Additionally, strength training did not have an effect on the spectral parameter values of HRV obtained in both groups. Strength training was not able to alter HRV autonomic modulation in women with PCOS, however may reduce testosterone levels and T/A ratio.

Effects of n-6 and n-3 polyunsaturated acid-rich soybean phosphatidylcholine on membrane lipid profile and cryotolerance of human sperm.

OBJECTIVE: To study the effects of n-6 and n-3 polyunsaturated acid-rich soybean phosphatidylcholine (soy-PC) on sperm cryotolerance with regard to sperm membrane lipid profile, membrane surface integrity, and routine semen parameters. DESIGN: Experimental study. SETTING: University-affiliated tertiary hospital. PATIENT(S): A total of 20 normospermic fertile men. INTERVENTION(S): Semen samples examined for differences in semen parameters, sperm membrane lipid profile, and plasma membrane surface both before and after cryopreservation using basic freezing medium with N-tris(hydroxymethyl)-methyl-2-aminoethane sulfonic acid (TES) and tris-(hydroxymethyl)-aminomethane (TRIS) supplemented with purified soy-PC (TEST-PC) or egg yolk (TEST-Y), both alone or in association (TEST-Y-PC). MAIN OUTCOME MEASURE(S): Conventional semen parameters and membrane lipid profile by matrix-assisted laser/desorption ionization mass spectrometry (MALDI-MS). RESULT(S): Postthaw sperm cell motility, vitality, and morphology parameters were similar for soy-PC (TEST-PC) and egg yolk (TEST-Y) cryoprotectants. However, sperm exposed to TEST-Y-PC presented better kinetic parameters, which were similar to the original quality of the fresh semen. Human sperm MALDI-MS lipid profiles revealed that the relative abundance of glycerophospholipids of m/z 760.44 [PC (34:1)+H]+, 781.55 [SM (20:0) +Na]+, 784.55 [PC (36:3) +H]+, 806.64 [PC (38:6) +H]+, 807.64 [SM (22:1) +Na]+, and 809.64 [SM (22:0) +Na]+ increased in soy-PC samples (TEST-PC). Nonetheless, only one lipid (m/z 781.55, [SM (20:0) +Na]+) statistically significantly changed when sperm was cryopreserved in TEST-Y-PC. CONCLUSION(S): Sphingomyelin was defined as a prospective biomarker of soy-PC treatment, and it could be related to the positive cryoprotective effects of soy-PC in human sperm, opening new perspectives to design of a more efficient synthetic cryoprotectant medium containing purified egg yolk biomolecules combined with soy-PC.

Gonadotropin and Estradiol Levels after Leuprolide Stimulation Tests in Brazilian Girls with Precocious Puberty.

STUDY OBJECTIVE: To determine the best cutoff value on the leuprolide stimulation test for the diagnosis of central precocious puberty (CPP) in a Brazilian population. DESIGN, SETTING, AND PARTICIPANTS: This observational study included 60 girls with CPP, as shown on the basis of serum concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) before and 3 hours after subcutaneous administration of 500 µg leuprolide acetate and by measuring serum estradiol concentrations 24 hours later. Six months later, each subject was clinically evaluated to determine whether she had experienced progressive or nonprogressive puberty. MAIN OUTCOME MEASURES: Analyzing the best cutoff for LH after subcutaneous administration of 500 µg leuprolide acetate. RESULTS: The best cutoff was a 3-hour LH level of greater than 4.0 mIU/mL, providing the highest sensitivity (73%) and specificity (83.1%), whereas a 3-hour LH level greater than 8.4 mIU/mL had a specificity of 100%. A 24-hour E2 concentration greater than 52.9 pg/mL had a sensitivity of 68% and a specificity of 74%. There was no association between pubertal development and disease progression. Signs such as thelarche and pubarche did not determine the evolution of the disease (P = .17). Clinical condition was associated with bone age/chronological age (P = .01), basal LH (P < .01), 3-hour LH (P = .02), baseline LH/FSH indices (P < .01) and after 3 hours (P < .01), and E2 at 24 hours (P = .02). CONCLUSION: The optimal parameter indicating hypothalamic-pituitary-gonadal axis activation in our sample was a 3-hour LH level greater than 4.0 mIU/mL. A diagnosis of CPP, however, should be based on a set of criteria and not on an isolated measurement, because typical laboratory findings associated with CPP may not be present in all patients.

Use of a Gonadotropin-releasing Hormone Analog to Treat Idiopathic Central Precocious Puberty Is Not Associated with Changes in Bone Structure in Postmenarchal Adolescents.

STUDY OBJECTIVES: To evaluate bone quantity and quality in postmenarchal adolescents treated for idiopathic central precocious puberty (CPP) in childhood with a gonadotropin-releasing hormone analog (GnRHa) and to determine the serum concentrations of bone remodeling markers. DESIGN AND PARTICIPANTS: This cross-sectional study included 53 postmenarchal adolescent girls who were divided into 2 groups: 27 adolescents who were treated with GnRHa in childhood for idiopathic CPP (the CPP group) and 26 women who presented with physiological development of secondary sex traits (the control group). INTERVENTIONS: None. MAIN OUTCOME MEASURES: Weight, height, body mass index, age at menarche, time since menarche, body composition, bone mineral density (BMD), bone quality, and serum insulin, glucose, osteocalcin, and carboxyl-terminal telopeptide of type I collagen concentrations were compared in the 2 groups. BMD data were analyzed by using both dual-energy x-ray absorptiometry (DXA) and osteosonography, and body composition was measure with the use of DXA and electrical bioimpedance. RESULTS: BMD and bone quality did not differ significantly between the CPP and control groups when analyzed by using DXA or osteosonography. Serum osteocalcin concentration was significantly lower (P = .02) in the CPP than in the control group. Insulin was higher in the CPP group, and hyperinsulinemia was an independent predictor of bone quantity and quality assessed by using osteosonography. Body mass index and percent fat were determined by using DXA, and the duration of use of GnRHa treatment and the time since GnRHa discontinuation were not independent predictors of bone quantity and quality. CONCLUSION: Postmenarchal adolescents treated with GnRHa for CPP in childhood did not show a reduction in bone quantity or quality.

Effect of infertility on the sexual function of couples: state of the art.

OBJECTIVE: Assess the state of the art on the relationship between infertility and the sexual function of couples. DATA SOURCES: The PubMed, Lilacs, and Google Scholar databases were searched for articles that assessed the sexual function of infertile couples (IC). Recent patents on this subject were assessed. STUDY SELECTION: Quantitative studies published in the English language (case-control, cross-sectional, cohort, multicenter, observational studies, randomized controlled trials, meta-analyses, systematic reviews) that used structured and semi-structured questionnaires for quantitative assessment of the sexual function of infertile couples were identified using the search terms: "infertile couple" and "sexuality", "sexual dysfunction", "sexual function", "sexual disorder", "hypoactive sexual desire". DATA EXTRACTION: One researcher identified 12 studies, and extracted data on 1871 IC. Five studies used different instruments to assess different aspects of sexual function and 7 studies assessed sexual function based on sub-domains of instruments used to evaluate marital relationships. DATA SYNTHESIS: Incongruent results due to different objectives and methodologies, the lack of specific questionnaires to assess sexual function, and uncontrolled social and relationship variables that could have interfered with sexual function were evident in most studies. CONCLUSION: The lack of standardized methodology or validated tools in most studies prevents to establish the impact of infertility on the sexual function of IC.

Current research on how infertility affects the sexuality of men and women.

OBJECTIVE: To assess data published from 2000 to 2010 on the effect of infertility on the sexual function of men and women. DATA SOURCES: The PubMed, Lilacs and Embase databases were searched for scientific articles assessing the sexual response of couples during infertility treatment. STUDY SELECTION: Studies selected for this review were published in English and conducted in human beings; articles included meta-analyses and cross-sectional or cohort studies that used objective measurement tools to quantitatively assess the data. DATA EXTRACTION: Seven studies met the inclusion criteria for this review. DATA SYNTHESIS: Infertility is a major risk factor for sexual problems in both men and women. CONCLUSION: Infertile couples are at higher risk of sexual dysfunction than fertile couples. We also describe several recent patents.

Low-dose transdermal hormone therapy does not interfere with the blood pressure of hypertensive menopausal women: a pilot study.

OBJECTIVES: To determine the effects of low-dose transdermal hormone therapy (HT) on systolic (SBP) and diastolic (DBP) blood pressure (BP) evaluated by 24-h ambulatory blood pressure monitoring (ABPM) in hypertensive postmenopausal women. METHODS: The study was conducted on 24 hypertensive postmenopausal women aged, on average, 54 years and under treatment with enalapril maleate (10-20 mg/day) combined or not with hydrochlorothiazide (25 mg/day). Thirteen women used a transdermal adhesive containing estradiol and norethisterone (25 and 125 mug active substance/day, respectively) and 11 did not receive HT. ABPM, lipid profile, and climacteric symptoms were evaluated before and 3 and 6 months after treatment. RESULTS: After 3 and 6 months of follow-up, there was a statistically significant reduction of the Blatt-Kupperman menopausal index in the treated group (19.6+/-8.3 vs. 9.6+/-5.9 vs. 9.7+/-7.0; P=0.01). No significant difference in any of the ABPM variables (areas under the systolic and diastolic curves, mean SBP and DBP, SBP and DBP loads and wakefulness-sleep variation) or in the lipid profile was observed between or within groups at the three time points studied. CONCLUSION: Low-dose transdermal HT administered for 6 months was effective in improving climacteric symptoms and did not change BP values or circadian pattern in postmenopausal women with mild-to-moderate arterial hypertension taking antihypertensive medications.

Effect of peritoneal fluid from patients with minimal/mild endometriosis on progesterone release by human granulosa-lutein cells obtained from infertile patients without endometriosis: a pilot study.

OBJECTIVE: To evaluate the effect of peritoneal fluid (PF) from women without and with minimal/mild endometriosis on progesterone (P) release by cultured human granulosa-lutein cells obtained from infertile patients without endometriosis submitted to ovarian hyperstimulation for in vitro fertilization (IVF). STUDY DESIGN: A pilot study was performed. Human granulosa-lutein cells, obtained from 11 infertile patients without endometriosis (tubal or male factors of infertility) submitted to ovarian hyperstimulation for IVF, were cultured without PF (basal production) and with increasing volumes of steroid-extracted PF samples from 11 patients with endometriosis and 11 patients without endometriosis. Progesterone (P) levels in the media after 72 h culture were measured by chemoluminescence assay. The non-parametric Mann-Whitney-test was used for statistical analysis. RESULTS: PF from patients without endometriosis stimulated P release in a dose-dependent manner up to the dose of 100 microl/ml (10% concentration) when compared with basal production (without adding PF). P release was similar in cultures stimulated with PF from patients with or without endometriosis at 1% (10 microl/ml) and 5% (50 microl/ml) concentrations. At 10% concentration, there was a non-statistically significant reduction in progesterone release by granulosa cells stimulated with PF from patients with endometriosis. PF from patients with endometriosis significantly reduced P release at 30% concentration (300 microl/ml). CONCLUSIONS: PF stimulates P release by human granulosa-lutein cells in a dose-dependent manner. However, higher concentrations of PF from patients with minimal/mild endometriosis reduce P release, suggesting it contains factors that may compromise ovarian steroidogenesis.

Gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period.

STUDY OBJECTIVE: To determine the presence of impaired gonadal function in adolescent patients submitted to chemotherapy during childhood or during the pubertal period. DESIGN: A case series study of 28 patients aged 12 to 19 years with menarche at least 2 years before the study. SETTING: Tertiary care public hospital. PARTICIPANTS: Group I: 14 adolescents previously submitted to chemotherapy during the prepubertal or peripubertal period and with remission of oncologic disease for at least 2 years; Group II: 14 normal adolescents with no previous oncologic disease and with regular menstrual cycles. INTERVENTIONS AND MAIN OUTCOME MEASURES: Pubertal development, menstrual cycles and serum levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were determined during the early follicular phase. RESULTS: There were no differences between the two groups in terms of age at appearance of secondary sexual characteristics or age at menarche. Menstrual irregularity was detected in 7 of the 14 patients in Group I, all 8 of whom presented oligomenorrhea. There were no differences in LH levels between the two groups (P = 0.55), although mean FSH levels were higher in Group I than in Group II (6.71 +/- 2.99 mIU/ml vs. 3.83 +/- 2.01 mIU/ml, P = 0.01). CONCLUSION: Although girls submitted to chemotherapy during the prepubertal or peripubertal period presented normal sexual development, the incidence of oligomenorrhea was higher than expected for their age, and FSH levels, although within normal limits, were higher than those seen in normally cycling girls.

Agreement among insulin sensitivity indexes on the diagnosis of insulin resistance in polycystic ovary syndrome and ovulatory women.

OBJECTIVE: The objective was to compare agreement on the diagnosis of insulin resistance (IR) among insulin sensitivity indexes in both ovulatory women and those with polycystic ovary syndrome (PCOS). STUDY DESIGN: In an observational study, the 75-g oral glucose tolerance test was performed in 105 women with PCOS and 51 ovulatory women. The insulin sensitivity indexes used were insulin quantitative sensitivity check index (QUICKI), 1/homeostasis model assessment-insulin resistance (1/HOMA-IR), area under curve for insulin (AUC-I), and the Matsuda insulin sensitivity index (COMP). For the IR diagnosis we used cut-off values described in recent publications (insulin >12 microIU/ml, 1/HOMA-IR <0.47, QUICKI < or =0.333, AUC-I > or =7000 microIU/ml 120 min, and COMP <4.75. RESULTS: Excellent agreement was assessed among insulin, QUICKI, and 1/HOMA-IR. However, the rate of IR detected by these indexes in the PCOS group (44.8-51.4%) was lower than expected. New cut-offs were then determined based on COMP results. Using these values, 1/HOMA-IR and QUICKI showed excellent agreement (kappa=0.83) with COMP. CONCLUSION: The observed agreements among insulin, QUICKI and 1/HOMA-IR were higher than 93%. Therefore, clinicians may choose any of those obtaining similar results. For clinicians who prefer COMP, but are looking for a simpler test to detect IR in PCOS women, the use of QUICKI and 1/HOMA-IR with the new cut-offs seems reasonable.

Controlled ovarian stimulation with exclusive FSH followed by stimulation with hCG alone, FSH alone or hMG.

OBJECTIVE: To assess if low-dose hCG is similar to hMG and to rFSH in the late follicular phase. STUDY DESIGN: In a prospective randomized controlled trial, 51 patients undergoing controlled ovarian stimulation received ovarian priming with rFSH and then received hCG (200 IU/day) (hCG group, n=17), hMG (225 IU/day) (hMG group, n=17) or rFSH (200 IU/day) (FSH group, n=17) in the late stage of follicular development. Parameters of follicular response and serum estradiol, progesterone and testosterone levels were assessed. RESULTS: Pre-ovulatory ovarian follicle occurrence and length of treatment were similar among the three treatment groups. Serum progesterone level on the day of pre-ovulatory hCG was significantly higher in the hCG group than in the hMG or rFSH group. Clinical pregnancy rates were similar for all groups. The total cost of treatment was significantly lower for the hCG group than for the groups supplemented with hMG or rFSH. CONCLUSIONS: LH in the form of low-dose hCG during the late follicular phase induced the same follicular pattern as hMG and rFSH after ovulation induction. The procedure using hCG produced pregnancy rates similar to those obtained using hMG and rFSH, even though the patients showed higher serum progesterone levels on the hCG day.

Vascular endothelial growth factor in the plasma, follicular fluid and granulosa cells of women with endometriosis submitted to in vitro fertilization--a pilot study.

Vascular endothelial growth factor (VEGF), a potent angiogenic factor that is altered in endometriosis, supports the immunological mechanism involved in this disease. The aim of the present study was to assess VEGF concentration in the plasma, follicular fluid (FF) and culture medium (CM) of granulosa cells from patients with endometriosis submitted to in vitro fertilization (IVF). A case-control study was conducted on 14 patients with endometriosis and 14 women without endometriosis submitted to IVF. Peripheral blood samples were collected before and after administration of human chorionic gonadotropin (hCG), in addition to FF and CM samples. Plasma VEGF levels increased after hCG administration in women with endometriosis and in controls, but were significant only in controls. VEGF levels were lower in FF but were significantly increased in the CM of patients with endometriosis. There was no correlation between VEGF and age, response to ovarian stimulation, oocyte or embryo quality, and pregnancy result. The increase of VEGF levels after hCG in both groups demonstrated a positive effect of this hormone on VEGF. VEGF in the FF and CM presented opposite results in endometriosis, suggesting that granulosa cells may show a different behavior in vivo and in vitro.