Body Image and Other Mood Vulnerabilities in Adolescents with Polycystic Ovary Syndrome and Metabolic Alterations.

INTRODUCTION: Psychological vulnerability is a relevant component of polycystic ovarian syndrome (PCOS), but it is still under-explored, especially during adolescence. The aim of this study was to describe a selection of psychometric characteristics in a clinical sample of Italian adolescents with PCOS. Moreover, we reported the associations of body image, eating attitudes, and mood with metabolic features. METHODS: Our sample included 128 adolescent girls (age range: 14-19 years) with PCOS. Validated psychometric questionnaires were administered: State Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Body Attitude Test (BAT), Bulimia Investigation Test (BITE), Eating Attitudes Test (EAT), and Perceived Stress Scale (PSS). RESULTS: Anxiety was the most prevalent mood disorder (63.1% trait anxiety and 57% state anxiety). Our cohort also showed a high prevalence of depression (39.1%), body image dissatisfaction (49.2%), disordered eating (11.7%), and bulimic risk (41.4%). PCOS adolescents with obesity and insulin resistance (IR) had statistically significant higher body image distress compared to those with normal weight and without IR (p < 0.001). The Sobel test for mediation showed that body image dissatisfaction mediates the relationship between state anxiety and bulimic risk (Z = 3.42, p < 0.001) and between depression and bulimic risk (Z = 4.59, p < 0.001). CONCLUSIONS: A considerable number of patients with PCOS experience psychological disorders during adolescence. IR and obesity play a role in the distress associated with body image, further contributing to psychological vulnerability, especially in the bulimic domain. A comprehensive biopsychosocial approach in adolescents with PCOS represents the basis for effectively managing and preventing complications arising from both psychological and biological disorders in adulthood.

Insights into the vulvar component of the genitourinary syndrome of menopause (GSM).

Genitourinary syndrome of menopause is a comprehensive term that groups genital, urinary and sexual signs and symptoms mainly due sex hormone deficiency and aging, with a crucial impact on quality of life of midlife women. While this broad definition captures the common underlying physiopathology and the frequent overlap of symptomatology, improving knowledge about different components of genitourinary syndrome of menopause may be relevant for individualized treatment, with possible implications for efficacy, compliance and satisfaction. This narrative review focuses on the vulvar component of genitourinary syndrome of menopause, highlighting anatomical and functional peculiarities of the vulva that are responsible for some of the self-reported symptoms, as well as specific signs at physical examination. Increasing evidence points towards a pivotal role of vulvar vestibular health in the occurrence of sexual pain, one of the most common and distressing symptoms of genitourinary syndrome of menopause, which should be evaluated with validated scales taking a biopsychosocial perspective. This is an essential step in the recognition of different phenotypes of genitourinary syndrome of menopause and in the assessment of the most effective diagnostic and therapeutic algorithm. Menopausal vulvar health deserves more research into tailored non-hormonal and hormonal treatment options.

Efficacy and safety of a device that combines multipolar radiofrequency with pulsed electromagnetic field for the treatment of vulvovaginal atrophy: a randomized, sham-controlled trial.

BACKGROUND: Vulvovaginal atrophy (VVA) negatively affects the sexual well-being and quality of life of postmenopausal women, yet it is underreported and undertreated. AIM: The study sought to investigate the efficacy and safety of a nonablative, noncoagulative multipolar radiofrequency (RF) and pulsed electromagnetic field-based device (PEMF) in treatment of symptoms related to VVA. METHODS: Seventy-six women ≥19 years of age with symptoms associated with VVA were enrolled into this prospective, randomized, sham-controlled, multicenter clinical study. Subjects were randomized to receive 3 RF + PEMF treatments (active group) or sham treatments (sham group) delivered to vaginal tissue at monthly intervals. The Vaginal Health Index (VHI), along with the Female Sexual Function Index (FSFI), subject sexual satisfaction and vaginal laxity (VL) score, treatment-associated pain, and adverse events were assessed at 4 follow-up (FU) visits between 1 and 12 months after treatment. OUTCOMES: Changes from baseline VHI, pH, FSFI, VL, and sexual satisfaction scores between the active and sham groups were compared before and after treatment. RESULTS: Mean VHI scores in the active group were significantly better compared with the sham group after treatment at all but the last FU visit (P < .001). A greater decrease in pH (active over sham) was seen at 1 and 4 months after treatment (P < .05). FSFI improvement was shown in the active group; however, it was not significantly better than sham improvement at all FU visits. Subject sexual satisfaction in the active group showed better improvement over sham at all FU visits (P < .05), while VL evaluations saw greater improvement in the active group at 4, 6, and 12 months posttreatment (P < .05). Treatment satisfaction was greater in the active group and pain was minimal in both groups. No serious adverse effects were reported. CLINICAL IMPLICATIONS: As a noninvasive alternative to traditional surgical and topical procedures, 3 sessions of noninvasive combination RF/PEMF safely demonstrated improvement in symptoms related to VVA. STRENGTHS AND LIMITATIONS: This study was strengthened by the randomized, sham-controlled design; large sample size; and extended FU period. The study assessments were decreased at later FU visits due to the global COVID pandemic, and this was a key limitation to the study. CONCLUSION: Nonablative, noncoagulative multipolar RF/PEMF therapy was safe, improved symptoms associated with VVA, and improved female sexual function while yielding high subject satisfaction.

Perimenstrual Asthma and Premenstrual Disorders in Adolescents with Asthma.

BACKGROUND: Asthma is a common chronic disease in pediatric patients, and perimenstrual asthma (PMA), refers to the worsening of asthma symptoms during the perimenstrual period, mainly reported in adult women. However, there is limited information regarding the exacerbation of symptoms in the presence of premenstrual disorders (PMDs) in adolescents. The aim of this pilot observational study was to investigate the frequency and potential association of PMA and PMDs in a clinical sample of adolescents with asthma. PATIENTS AND METHODS: The study included 50 adolescents (aged 12-18 years, mean 16.08 ± 2.35) with asthma and at least 2 years of gynecological age. The participants completed the Asthma Control Test (ACT) to assess asthma control (considered pathological if ACT score < 20) and the modified Premenstrual Symptoms Screening Tool for Adolescents (PSST-A) to evaluate PMDs. RESULTS: A total of 75.5% of adolescents reported PMA. The prevalence of premenstrual symptoms did not significantly differ between the PMA and no-PMA group. Among the study sample, 38.7% experienced symptoms indicative of moderate/severe premenstrual syndrome, and 8.1% exhibited symptoms of premenstrual dysphoric disorder. Compared with the no-PMA group, patients with PMA showed a significant impairment in daily and home activities (P = .03 and P = .02, respectively) and exhibited a difference in the frequency of asthma symptoms (P < .001) and medication use (P ≤ .01). CONCLUSION: Perimenstrual worsening of asthma symptoms may be common in adolescents with a severe form of asthma. Prospective data collection through menstrual diaries is necessary to further explore the association between PMA and PMDs. Identifying early risk factors for PMA could facilitate the development of preventive strategies and early interventions for adolescents with asthma.

Sexual health and contraception in the menopause journey.

Women may experience changes in sexuality across menopause, because at this step in life hormone deficiency interacts with several determinants in a bio-psycho-social perspective. Healthcare providers should inform women about menopause impact on sexuality and be proactive during consultation in disclosing sexual concerns that would require a targeted assessment. Sexual symptoms become more frequent as women age, but they do not always translate into sexual dysfunction diagnosis, for which distress is required. It is important to recognize conditions that may increase the risk of dysfunctional response to menopause challenges in order to promote sexual longevity through counselling and specific management. In this review, we report key elements for a comprehensive assessment of sexual health around menopause, with a focus on genitourinary syndrome of menopause (GSM) and hypoactive sexual desire disorder (HSDD), representing well identified clinical conditions affecting sexuality at midlife and beyond. We also address the issue of contraception across the menopausal transition, highlighting risks and benefits, and possible implications on sexual function.

The Role of Irisin throughout Women's Life Span.

Since its discovery, much attention has been drawn to irisin's potential role in metabolic and reproductive diseases. This narrative review summarizes and updates the possible role played by this fascinating molecule in different physiological (puberty and menopause) and pathological (polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhea (FHA), endometriosis, and gestational diabetes) conditions that can affect women throughout their entire lives. Irisin appears to be an important factor for the hypothalamic-pituitary-gonadal axis activation, and appears to play a role in the timing of puberty onset. Serum irisin levels have been proposed as a biomarker for predicting the future development of gestational diabetes (GDM). Its role in PCOS is still controversial, although an "irisin resistance" mechanism has been hypothesized. In addition to its impact on metabolism, irisin also appears to influence bone health. Irisin levels are inversely correlated with the prevalence of fractures in postmenopausal women. Similar mechanisms have also been postulated in young women with FHA. In clinical settings, further controlled, prospective and randomized clinical trials are needed to investigate the casual relationship between irisin levels and the conditions described and, in turn, to establish the role of irisin as a prognostic/diagnostic biomarker or a therapeutic target.

Impact of climate and environmental change on the menopause.

The huge impact of climate change on humankind is multidimensional, and includes direct and indirect challenges to the physical, psychological and socio-cultural wellbeing. Women may be more vulnerable to climate-sensitive diseases, but little attention has been paid to specific needs and challenges associated with the menopause transition. The increase in average and extreme temperatures may modulate the manifestation of vasomotor symptoms; in particular, environmental temperature and seasonality may affect hot flushes and night sweats. However, more research is needed to define the impact of climate-related factors among the determinants influencing the individual experience of menopause. In addition, increased exposure to environmental pollution and toxins may also have a role in the modulation of ovarian aging mechanisms, possibly influencing timing of menopause. Finally, both air pollution and menopause transition are associated with unfavorable modifications of cardio-metabolic, bone and cognitive health, and account should be taken of these in the evaluation of the individual woman's health vulnerabilities. Overall, the evidence reported in this narrative review supports the need for specific strategies aimed at reducing the burden of climate and environmental change on menopausal women. Healthcare providers should promote behavioral measures that reduce anthropogenic climate change and at the same time have a beneficial role on several domains of physical and psychological wellbeing. From this perspective, menopause represents a golden moment to implement virtuous behaviors that will benefit at the same time women's longevity and the planet.

Genitourinary Syndrome of Menopause in Breast Cancer Survivors: Current Perspectives on the Role of Laser Therapy.

Genitourinary syndrome of menopause (GSM) is a frequent consequence of iatrogenic menopause or anti-estrogenic adjuvant therapies in breast cancer survivors (BCSs). GSM may profoundly affect sexual health and quality of life, and a multidimensional unique model of care is needed to address the burden of this chronic heterogeneous condition. Severe symptoms may be insufficiently managed with non-hormonal traditional treatments, such as moisturizers and lubricants, recommended as the first-line approach by current guidelines, because concerns exist around the use of vaginal estrogens, particularly in women on aromatase inhibitors (AIs). Vaginal laser therapy has emerged as a promising alternative in women with GSM who are not suitable or do not respond to hormonal management, or are not willing to use pharmacological strategies. We aim to systematically review current evidence about vaginal laser efficacy and safety in BCSs and to highlight gaps in the literature. We analyzed results from 20 studies, including over 700 BCSs treated with either CO2 or erbium laser, with quite heterogeneous primary outcomes and duration of follow up (4 weeks-24 months). Although evidence for laser efficacy in BCSs comes mostly from single-arm prospective studies, with only one randomized double-blind sham-controlled trial for CO2 laser and one randomized comparative trial of erbium laser and hyaluronic acid, available data are reassuring in the short term and indicate effectiveness of both CO2 and erbium lasers on the most common GSM symptoms. However, further studies are mandatory to establish long-term efficacy and safety in menopausal women, including BCSs.

No-daily hormonal contraception today: general overview and application in specific clinical settings.

No-daily hormonal contraception includes short-acting reversible contraceptives (SARC), which contain estrogen and progestin (vaginal ring and transdermal patch), and long-acting reversible contraceptives (LARC), which contain only progestin (levonorgestrel-releasing intrauterine device and etonogestrel subdermal implant). No-daily hormonal contraceptives are reversible, avoid oral daily intake and have high contraceptive efficacy. They offer advantages over the traditional oral route, increasing user compliance, and reducing forgetfulness. Furthermore, they have several non-contraceptive benefits. This review aims to highlight the strengths of choices other than the traditional 'pill', with the goal of implementing contraceptive counseling, which should be personalized and tailored to each woman. Different subsets of patients may use no-daily contraception at different stages of their lives, with the option of either LARC or SARC. Specific contexts for its use are adolescence, perimenopause, obese women, eating disorders or intestinal malabsorption, breastfeeding, and post voluntary termination of pregnancy. Non-daily contraceptives can be an attractive alternative to the daily contraceptive pill, with benefits that are relevant to each woman desiring contraception, especially in unique and specific settings where customization of the contraceptive method is essential.

Is now the time to reconsider risks, benefits, and limitations of estrogen preparations as a treatment for menstrually related migraine?

INTRODUCTION: Estrogen fluctuations modulate pain threshold and play a pivotal role in the central and peripheral pathogenesis of menstrually related migraine (MRM). Estrogen-withdrawal during the perimenstrual phase of a spontaneous menstrual cycle or the hormone-free interval (HFI) of hormonal treatments seems to be the culprit. AREA COVERED: The authors report the most relevant data on risks, benefits, and limitations of exogenous estrogens as a treatment for MRM considering gynecological comorbidities associated with chronic pelvic pain that may be effectively managed by the use of combined hormonal contraception (CHC). Given that migraine and CHC are both currently known as independent risk factors for stroke, levels of evidence contraindicate CHC in women with migraine with aura, whereas quality of evidence is low in women with migraine without aura, including MRM. Continuous/extended/flexible CHC regimens, shorter HFI, or estrogens supplementation during the HFI/perimenstrual spontaneous phase may be beneficial in women with MRM. EXPERT OPINION: Safety is a main issue, and it is mandatory to investigate the impact of CHC containing natural estrogens, instead of ethinylestradiol, on clinical pattern of MRM and cardiovascular associated risk. Reproductive characteristics may be relevant and should be considered in a multidisciplinary approach to increase the power of endocrine management in MRM.

Women's attitudes about combined hormonal contraception (CHC) - induced menstrual bleeding changes - influence of personality traits in an Italian clinical sample.

OBJECTIVES: We investigated the attitudes to change the frequency of menstrual bleeding by using combined hormonal contraception (CHC). Personality characteristics were also explored. METHODS: We conducted a cross-sectional study in two university hospitals in northern Italy. Current, past and never CHC users (n = 545; age 18-44 years) completed a self-administered semi-structured questionnaire and the Ten-Item Personality Inventory (TIPI). RESULTS: Forty-five percent of responders (n = 301) would prefer to change their bleeding frequency by using CHC. A flexible regimen was the preferred choice (n = 80; 33%) followed by extended regimens to bleed every 3 months (n = 54; 22%) or to never bleed (n = 43; 18%). The main positive reasons were to avoid dysmenorrhea (43%) and have more freedom in sexual (36%) and active (35%) life, whereas the main reason for a negative attitude was 'menstrual rhythm is natural' (59%). Age had a significant influence on women's willingness to change menstrual frequency by using CHC [>39 years (57%), 30-39 years (31%) and <30 years (46%)] (χ2: 9.1; p = 0.01). Never users significantly reported a more negative attitude (71%) in comparison with past (51%) and current users (49%) (χ2: 18.7; p = 0.001). Personality traits played a role, with higher scores of openness (p = 0.005) and extraversion (p = 0.001) in women with a positive attitude. CONCLUSIONS: Almost half of our study sample reported a preference for changing their menstrual pattern by using CHC. Flexibility was the preferred choice across age and use of CHC. Personality characteristics (openness and extroversion) might influence attitudes toward CHC-induced menstrual bleeding changes.

Pharmacotherapy for female sexual dysfunctions (FSDs): what is on the market and where is this field heading?

INTRODUCTION: Female sexual dysfunctions (FSDs) are common in women of any age and have a huge impact on quality of life and relationships. They have a multifaceted etiology limiting the development of pharmacotherapies with a high rate of effectiveness. Safety issues are also a concern. AREAS COVERED: The authors report the most recent advances in pharmacotherapy for premenopausal and postmenopausal women with a main focus on hypoactive sexual desire disorders (HSDD) and associated sexual symptoms. Good levels of evidence have emerged for psychoactive agents, such as flibanserin and bremelanotide, as well as hormonal compounds (transdermal testosterone). The authors also report briefly on intravaginal DHEA (prasterone), local estrogen therapy (LET), and ospemifene to manage effectively vulvovaginal atrophy/genitourinary syndrome of menopause (VVA/GSM). In addition, they discuss promising therapeutic options highlighting the main reasons that hamper the availability of new labeled products. Finally, they include the importance of the multimodal approach to address FSDs. EXPERT OPINION: Approved pharmacotherapies for FSD are limited. Validated multidimensional instruments and adequate objective measures of physical and mental responses to sexual external and internal incentives are mandatory to identify women suitable to chronic or on-demand treatments and to assess their pattern of response in research and practice.

Relationship between personality traits and sexual function in symptomatic postmenopausal women.

INTRODUCTION: Female sexual function relies on a complex interplay of physical, psychosocial, and neurobiological factors. Over the last decades, increasing attention has been paid to the influence of personality traits on general health and many aspects of quality of life, including sexuality. OBJECTIVE: To assess whether dimensions of the personality are related to the domains of sexual function (desire, arousal, lubrication, orgasm, satisfaction, and pain) in symptomatic postmenopausal women. Mood was also investigated to explore its association with female sexual dysfunction (FSD). METHODS: Validated questionnaires to assess sexual function [the Female Sexual Functioning Index (FSFI)], mood [the State-Anxiety Inventory (STAI), and Zung Self Rating Depression Scale (SDS)], and personality traits [the Tridimensional Personality Questionnaire (TPQ)] were filled in by 130 early postmenopausal women experiencing hot flushes (≥30/week). RESULTS: 61.5 % (n = 80) of the women had an FSFI total score lower than 26.55, the standard cut-off for FSD. A clinical state of anxiety was present in 53.8 % (n = 70), whereas only 12.3 % (n = 16) showed clinically relevant depressive symptoms. According to the FSFI cut-off score, women with sexual disorders had statistically significantly higher levels of anxiety, depression (p < 0.001 for both), and harm avoidance (HA) (p = 0.004) than women without such disorders. Significantly higher levels of anxiety were found in women in the lower quartile (LQ) of the distribution of the total FSFI score than in women in both the interquartile range (IQR) and in the upper quartile (UQ) (p < 0.05). Moreover, women in the UQ had a lower grade of depression and HA than others (p < 0.05). The Sobel test showed that the personality trait HA significantly mediated the relationship between anxiety and FSFI total score (Z = -2.19, p < 0.05) and between depression and FSFI total score (Z = -2.35, p < 0.05). CONCLUSIONS: The present data suggest the personality trait HA is relevant to sexual function and mediates the impact of mood on FSD in symptomatic menopausal women. In clinical practice, the use of validated psychometric tools for mood screening is useful to establish appropriate diagnosis and treatment of sexual disorders in menopausal women. Moreover, the assessment of personality traits could provide additional information that directs clinicians towards an increasingly tailored and multidimensional treatment of FSD.

Recent advances in understanding/management of premenstrual dysphoric disorder/premenstrual syndrome.

Premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) are common disorders of the luteal phase of the menstrual cycle and are characterized by moderate to severe physical, affective, or behavioral symptoms that impair daily activities and quality of life. PMS and PMDD have recently raised great interest in the research community for their considerable global prevalence. The etiology of PMS/PMDD is complex. Ovarian reproductive steroids (estradiol and progesterone) are considered pathogenetic effectors, but the key feature seems to be an altered sensitivity of the GABAergic central inhibitory system to allopregnanolone, a neurosteroid derived from progesterone produced after ovulation. Also, a reduced availability of serotonin seems to be involved. New insights point to a role for genetic and epigenetic modifications of hormonal and neurotransmitter pathways, and inflammation is the potential link between peripheral and neurological integrated responses to stressors. Thus, new therapeutic approaches to PMS/PMDD include inhibition of progesterone receptors in the brain (i.e., with ulipristal acetate), reduced conversion of progesterone to its metabolite allopregnanolone with dutasteride, and possible modulation of the action of allopregnanolone on the brain GABAergic system with sepranolone. Further research is needed to better understand the interaction between peripheral inflammatory molecules (cytokines, interleukins, C-reactive protein, and reactive oxygen species) and the brain neurotransmitter systems in women with PMS/PMDD. If confirmed, neuroinflammation could lead both to develop targeted anti-inflammatory therapies and to define prevention strategies for the associated chronic inflammatory risk in PMS/PMDD. Finally, the observed association between premenstrual disorders and psychological diseases may guide prompt and adequate interventions to achieve a better quality of life.

Role of Estrogens in Menstrual Migraine.

Migraine is a major neurological disorder affecting one in nine adults worldwide with a significant impact on health care and socioeconomic systems. Migraine is more prevalent in women than in men, with 17% of all women meeting the diagnostic criteria for migraine. In women, the frequency of migraine attacks shows variations over the menstrual cycle and pregnancy, and the use of combined hormonal contraception (CHC) or hormone replacement therapy (HRT) can unveil or modify migraine disease. In the general population, 18-25% of female migraineurs display a menstrual association of their headache. Here we present an overview on the evidence supporting the role of reproductive hormones, in particular estrogens, in the pathophysiology of migraine. We also analyze the efficacy and safety of prescribing exogenous estrogens as a potential treatment for menstrual-related migraine. Finally, we point to controversial issues and future research areas in the field of reproductive hormones and migraine.

Medical Treatment of Female Sexual Dysfunction.

Female sexual dysfunction (FSD) comprises multiple overlapping sexual disorders with a multifaceted cause within the frame of the biopsychosocial model. Health care providers can screen for FSD according to their level of expertise and deliver at least basic counseling before eventually referring to sexual medicine specialists for specific care. The therapeutic algorithm comprises a multidisciplinary approach, including pharmacologic and nonpharmacologic management. Flibanserin and bremelanotide are psychoactive agents indicated for the treatment of generalized acquired hypoactive sexual desire disorder (HSDD) in premenopausal women, whereas transdermal testosterone is effective on HSDD in postmenopausal women. Menopause hormone therapy (systemic and local) is the mainstay for individualized management of women at midlife.

Menopause and female sexual dysfunctions.

Biological and psycho-relational factors contribute equally to the development of sexual symptoms and associated distress, a key element to diagnose female sexual dysfunctions (FSDs) in menopausal women. Consultation at midlife represents an optimal time to discuss sexual life, and healthcare providers have to be proactive in rising the conversation, as patients may not report their sexual concerns spontaneously. An accurate sexual history is essential to characterize the primary symptom, determine the impact on patient's quality of life and identify risk and precipitating factors. Among FSDs, hypoactive sexual desire disorder is very frequent at midlife together with genitourinary syndrome of menopause, a chronic condition negatively affecting the full sexual response. A multidimensional approach targeted to the patient's characteristics, goals and expectations is mandatory and should start from educative counselling and correction of modifiable risk factors. When specific treatments are required, they should include non-pharmacological and pharmacological options, often prescribed in combination to address concomitantly the biological and psychosocial components of FSDs.

Perimenstrual Asthma in Adolescents: A Shared Condition in Pediatric and Gynecological Endocrinology.

Asthma is a frequent medical condition in adolescence. The worsening of the most common symptoms perimenstrually is defined as perimenstrual asthma (PMA). The cause of PMA remains unclear, but a role for hormonal milieu is plausible. Data on PMA in adolescents are limited, and its management is not fully established. We aimed to discuss the PMA phenomenon in young females from pathophysiology to preventive strategies, focusing on the relationship with the hormonal pattern. The fluctuation of estrogens at ovulation and before menstruation and the progesterone secretion during the luteal phase and its subsequent withdrawal seem to be the culprits, because the deterioration of asthma is cyclical during the luteal phase and/or during the first days of the menstrual cycle. Conventional asthma therapies are not always effective for PMA. Preventive strategies may include innovative hormonal contraception. Even a possible beneficial effect of other hormonal treatments, including estrogens, progestogens, and androgens, as well as leukotriene receptor antagonists and explorative approach using microbial-directed therapy, is considered. The underlying mechanisms, through which sex-hormone fluctuations influence asthma symptoms, represent a challenge in the clinical management of such a distressing condition. Further studies focused on young females are mandatory to promote adolescent health.