Rosana Maria Reis

REVIEWS: The Effects of Hypoestrogenism on the Vaginal Wall: Interference with the Normal Sexual Response

INTRODUCTIONnThe sexual response depends on the adequate function of all systems related to the genital and extra-genital organs. Physiological conditions such as menopause can interfere with sexual expression because of central and peripheral changes. Genital effects of estrogen include vaginal trophism, lubrication, and local pleasure sensation in the sexual arousal phase. Hypoestrogenism causes changes in the four layers of the vaginal wall that may result in dyspareunia and a loss in the quality of the genital arousal response.nnnAIMnThe purpose of this review is to highlight the changes in the vaginal wall caused by hypoestrogenism, its possible relationship with dyspareunia, and its repercussions for genital arousal. Treatments for hypoestrogenism are also discussed.nnnMETHODSnWe evaluated the data available in PubMed (1982-2008) and surveyed the reference list for relevant studies. Two reviewers analyzed the data independently. A study was considered to be of high quality if it had all three of the following characteristics: (i) prospective design; (ii) valid data; and (iii) adequate sample size. Reviews and experimental animal studies were also considered.nnnMAIN OUTCOME MEASURESnNormal genital morphology, hypoestrogenism and hormone replacement therapy were the focus of the studies reviewed in this paper.nnnRESULTSnAtrophy of the vaginal wall may be associated with dyspareunia and genital sexual arousal disorder, but psychological and sociocultural aspects must also be considered. Regardless, however, local estrogen therapy is useful in improving vaginal wall trophism and, thus, in improving the sexual response.nnnCONCLUSIONSnThere are many possible alterations in the structure of the vaginal wall that are related to estrogen deficiency that may require medical intervention beyond the usual strategies used to attain adequate sexual function. Physicians should attempt to treat these alterations, and more research is needed to elucidate the physiopathology of dyspareunia and genital sexual arousal physiology.

High prevalence of polycystic ovary syndrome in women born small for gestational age

BACKGROUNDnThere is evidence that intrauterine growth restriction, resulting in newborn girls that are small for gestational age (SGA), may be related to the onset of polycystic ovary syndrome (PCOS). Thus, we studied whether women born SGA have a higher prevalence of PCOS than women born appropriate for gestational age (AGA).nnnMETHODSnThis was a prospective birth cohort study of 384 women born at term between June 1, 1978, and May 31, 1979, in Ribeirão Preto, Brazil. After exclusion, 165 women effectively participated in this study, of whom 43 were SGA and 122 were AGA. The prevalence of PCOS was analysed. At a mean age of 29 years, the women agreed to follow the study protocol, which included: anamnesis, physical examination, serum tests [follicle stimulating hormone, luteinizing hormone, total and free testosterone, dehydroepiandrostenedione sulphate, 17-OH-progesterone, fasting insulin, sex steroid-binding globulin (SHBG) and fasting glucose] and pelvic ultrasound. Data regarding gestational age, birthweight, age at menarche and maternal data were obtained from the files of the cohort. The adjusted relative risk (RR) values of the SGA, insulin resistance, body mass index, maternal smoking and parity variables were analysed using Poisson regression with robust adjustment of variance for the prediction of PCOS.nnnRESULTSnThe prevalence of PCOS was higher in the SGA group than in the AGA group [adjusted RR = 2.44, 95% CI (1.39-4.28)]. Hyperandrogenism was more prevalent in the SGA women than in the AGA women (P = 0.011). Circulating SHBG was lower in the SGA women than in the AGA women (P = 0.041), but fasting insulinemia was similar in both groups.nnnCONCLUSIONSnThe prevalence of PCOS in SGA women was twice as high as in AGA women in our study population.

Altered sexual and reproductive functions in epileptic men taking carbamazepine.

INTRODUCTIONnEpileptic men may experience hormonal changes that may alter semen quality and sexual function. Alterations in male sexual and reproductive parameters may also be due to treatment with antiepileptic drugs to control seizures.nnnAIMSnTo evaluate serum hormone concentrations, semen quality, the frequency of sexual intercourse (FSI), and erectile function in men with epileptic seizures controlled by carbamazepine (CBZ).nnnMAIN OUTCOME MEASURESnThe five-question form of the International Index of Erectile Function (IIEF-5), and semi-structured questionnaire.nnnMETHODSnOne hundred and eighteen men, aged 18-45 years, were included in this controlled, cross-sectional study: 63 men taking CBZ (epileptic group) were compared to 55 healthy men (control group). Blood sample was collected to determine hormones concentrations. Erectile function and the frequency of sexual relations were assessed by using questionnaires. Sperm morphology was analyzed by examining the quality of the head, intermediate part and tail of the spermatozoa.nnnRESULTSnUsing the IIEF-5, we observed a significant association between erectile dysfunction (ED) and groups (P < 0.01), where epileptic men had 17.33 (95% CI 3.59, 83.52) odds to have erectile dysfunction. Adjusted odds ratio to group considering luteinizing hormone, prolactin, Serum total testosterone, androstenedione, and dehydroepiandrosterone, androstenedione levels and free androgen index, we observed only group effect where epileptic men had 10.47 (95% CI 2.75, 39.83) odds to have FSI < 3 times a week. Sperm vitality was altered in 27% of the epileptic subjects compared with 5.4% of the control group (P < 0.002). Sperm motility differed significantly between groups, with A + B motility ≤50% observed in 98.4% of the epileptic group and in 85.4% of the control group (P < 0.01). Sperm morphology <14% was observed in 93.7% of the epileptic men, compared with 34.6% of the controls (P < 0.001). CBZ users, showed less sexual intercourse then controls (P ≤ 0.001).nnnCONCLUSIONSnEpileptic men taking CBZ present with changes in hormonal levels, altered semen quality, ED, and a reduction in coital frequency.

Sexuality during the climacteric period.

BACKGROUNDnCultural, social, physiological and psychological factors may alter the course of sexual function in climacteric women.nnnOBJECTIVEnThe objective of the present literature review is to survey the prevalence of sexual dysfunctions in the climacteric and to establish the association between the organic and psychic changes that occur during this phase and sexual dysfunction. We also discuss potential treatments.nnnMETHODSnWe evaluated the data available in PubMed (1982-2008). For each original article, two reviewers analyzed the data independently and considered a study to be of high quality if it had all three of the following characteristics: prospective design, valid data and adequate sample size. Both reviewers extracted data from each of the 99 studies selected: 34 cross-sectional studies, 25 cohort studies, 9 trials, 31 reviews related to sexuality in pre- and post-menopausal women.nnnRESULTSnSexual dysfunction among climacteric women is widespread and is associated with bio-psychosocial factors. However, there is not enough evidence to correlate sexual dysfunction with a decrease in estrogen levels and biological aging. A strong association exists between climacteric genital symptoms and coital pain. There is, however, sufficient evidence demonstrating the benefits of local estrogen therapy for patients with genital symptoms.nnnCONCLUSIONnA significant decline in sexual function occurs in climacteric women, although it is still unclear whether this is associated with the known decrease in estrogen levels or with aging, or both. Relational factors may interfere with sexual function during this phase. The climacteric genital symptoms improve with estrogen replacement therapy, and positively influence sexual function. Further studies are needed to establish the actual impact of the decrease in estrogen levels and of aging on the sex life of climacteric women.

Doppler Study of the Uterine Arteries and Ovarian Stroma in Patients with Polycystic Ovary Syndrome

Doppler analysis of the uterine arteries and ovarian stroma was performed by transvaginal ultrasound in 24 patients with polycystic ovary syndrome (PCOS) and 22 ovulatory women. Vascularization of the ovarian stroma was more abundant in patients with PCOS than in control women, but no significant difference in the mean pulsatility index (PI) was observed between groups (1.14 ± 0.28 for the PCOS group and 1.05 ± 0.19 for the control group). The mean PI of the uterine arteries was significantly higher in the PCOS group (PI = 3.7 ± 0.8) than in the control group (PI = 2.9 ± 0.4). In the patients with PCOS, no correlation was observed between PI and luteinizing hormone, testosterone or androstenedione levels. Obesity had no effect on uterine artery PI, with no significant differences in this index when the 3 groups were subdivided into obese and non-obese groups.

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.

Changes in Sexual Function among Women with Polycystic Ovary Syndrome: A Pilot Study

INTRODUCTIONnPolycystic ovary syndrome (PCOS) appears to be related to sexual dysfunction, especially if associated with obesity. However, it is not clear whether obesity per se is an independent factor for sexual dysfunction. We hypothesized that obese polycystic ovary syndrome (OPCOS) patients have poorer sexual function than controls and nonobese polycystic ovary syndrome (NOPCOS) women.nnnAIMnTo assess the sexual function of women (either obese or nonobese) with PCOS compared to women with regular cycles.nnnMAIN OUTCOME MEASURESnThe main outcome measures were the Female Sexual Function Index (FSFI) and Free Androgen Index (FAI) values.nnnMETHODSnWe used a cross-sectional study design to evaluate 83 women, including 19 nonobese women without PCOS, 24 nonobese women with PCOS, 16 obese women without PCOS, and 24 obese women with PCOS. The FSFI questionnaire was used to gather data from all women, and free testosterone levels were determined and employed to calculate FAI values.nnnRESULTSnHigher androgen concentrations were evident in the PCOS groups compared to controls (NOC [nonobese control] 2.3 ± 0.7; OC [obese control] 2.1 ± 0.5; NOPCOS 3.1 ± 0.8; OPCOS 3.5 ± 1.2; P < 0.0001). This was also true for FAI, with the exception of obese controls and nonobese women with PCOS, in whom the levels were similar (NOC 4.9 ± 1.6; OC 6.5 ± 3.1; NOPCOS 7.5 ± 3.9; OPCOS 12.8 ± 5.2; P < 0.05). Evaluation of the total FSFI scores revealed that obese women without PCOS had below-normal sexual function scores, whereas both obese and nonobese women with PCOS had borderline scores compared to controls, who had normal FSFI findings. No association was observed between body mass index, the presence of PCOS, testosterone level, and FSFI score.nnnCONCLUSIONSnThe obese women in our sample were at a higher risk for sexual dysfunction and lower FSFI scores, and women with PCOS had borderline FSFI values, regardless of their obesity status. Based on this result, larger studies using the methods described in this pilot study are warranted to elucidate if obesity can impair sexual function in PCOS women.

Current Research on How Infertility Affects the Sexuality of Men and Women

OBJECTIVEnTo assess data published from 2000 to 2010 on the effect of infertility on the sexual function of men and women.nnnDATA SOURCESnThe PubMed, Lilacs and Embase databases were searched for scientific articles assessing the sexual response of couples during infertility treatment.nnnSTUDY SELECTIONnStudies 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.nnnDATA EXTRACTIONnSeven studies met the inclusion criteria for this review.nnnDATA SYNTHESISnInfertility is a major risk factor for sexual problems in both men and women.nnnCONCLUSIONnInfertile couples are at higher risk of sexual dysfunction than fertile couples. We also describe several recent patents.

Effects of metformin on serum insulin and anti-Mullerian hormone levels and on hyperandrogenism in patients with polycystic ovary syndrome.

Objective: To evaluate the relationship between serum anti-mullerian hormone levels (AMH) and insulin resistance (IR) before and after meformin treatment and to compare AMH levels of polycystic ovary syndrome (PCOS) women in the early follicular phase. Methods: Twenty PCOS women with IR, taking metformin 1500u2009mg/day for 8 weeks, and 16 non-PCOS controls were enrolled in this longitudinal study. Serum levels of AMH, insulin, glucose, testosterone, and quantitative insulin check index (QUICKI), were assessed before and after treatment in PCOS group. Results: AMH levels were higher in untreated PCOS (p < 0.0001), as were luteinizing hormone (LH) (p = 0.0004), testosterone (p = 0.0017) as well as 17-hydroxyprogesterone (p = 0.03). PCOS women show positive correlation between AMH and testosterone (R = 0.83; p < 0.0001) only prior to treatment. Metformin treatment, lead to a significant decrease in serum insulin (p = 0.0132) and testosterone (p = 0.0017) levels. However, no alteration in AMH levels was observed after treatment. Conclusion: Despite the improvement of metabolic parameters and the reduction of androgen levels, AMH levels did not change after metformin treatment. Maybe, the dose, and possibly the time of use, of metformin are factors associated with the reduction of AMH levels.

Endocrine Disrupters: Potential Risk Factors Affecting Sexual Function in Both Men and Women

Environmental pollution caused by chemicals such as fungicides, pesticides, and insecticides that can disrupt the endocrine system is a major health concern. Such endocrine disrupters mimic hormonal action; individual chemicals may have either an antiandrogenic or estrogen-like effect. These functions are potentially hazardous in terms of effects on the reproductive axis [1], leading to a reduction in serum thyroid hormone level and also reductions in the serum levels of gonadotropin, free testosterone, and estradiol. The estrogen and androgen deficiency is associated with reduced expression of sex steroid receptors and with attenuated genital blood flow and reduced vaginal lubrication, thus potentially causing abnormal sexual response [2–4]. In view of the alterations to the endocrine system caused by environmental pollutants, it is likely that such endocrine disrupters also affect the sexual responses of both men and women. However, this issue is poorly documented; only five studies assessing male sexual function after exposure to pollutants have appeared (Table 1). Four of these works [5–8] reported that sexual desire was reduced following exposure to phenothrin, lindane, dioxin, and pentachlorophenol, while the other report [9] found that erectile dysfunction was evident in men exposed to dioxin-like compounds. All the five studies assessed sexual function as a secondary outcome. Thus, the mechanism(s) by which such substances disrupt the male sexual response remains unknown. No study has examined the impact of environmental pollutants on sexual function in women. Notwithstanding the fact that research in this area is limited, accumulating evidence of an increased incidence of abnormal sexual development in humans and animals supports the notion that the sexual responses of both men and women may also be affected by pollutants. Therefore, further studies are urgently needed to explore the effects of endocrine disrupters on human sexual responses. Lucia Alves da Silva Lara Sexual Medicine Service, Department of Gynaecology and Obstetrics, Faculty of Medicine of Ribeirao Preto, Sao Paulo University, Ribeirao Preto, Brazil