Serum kisspeptin levels along reproductive period in women: is it a marker for aging?

OBJECTIVE: To demonstrate the change in serum kisspeptin levels during the reproductive period in healthy women and to investigate the relationship with other reproductive hormones. METHODS: One hundred thirty-one healthy women with normal menstrual history were included and serum kisspeptin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), estradiol (E2), and anti-Müllerian hormone (AMH) levels were determined on cycle day 3. The data were analyzed in 5-year age groups. RESULTS: Serum kisspeptin levels of all women were found to be significantly and negatively correlated with age (r= -0.458). The kisspeptin levels were the highest in the group of women aged between 20 and 24 years compared to other age groups above 25 years (p < .01, p < .001, p < .0005, p < .0005). There was not any significant correlation between serum kisspeptin levels and AMH, FSH, LH, TSH, E2, and body-mass index (BMI), respectively. The Scatter and Violin plots showed that most of the women over 35 years of age had serum kisspeptin levels under the level of 500 pg/ml. The kisspeptin levels of women over 35 years of age clustered closely as opposed to the kisspeptin levels of those below the age of 35, which were scattered. The median serum kisspeptin levels were found to be high in women below the age of 35 (p < .0005). CONCLUSION: In healthy women, serum kisspeptin level is the highest in the group of women aged between 20 and 24 years and declines with age. It tends to be below the level of 500 pg/ml in women over the age of 35.

Non-ablative Erbium (YAG) and Neodymium (YAG) Laser Treatment for Anal Incontinence and Vaginal Atrophy: A Case Study.

In this case study, a 68-year-old woman with anal incontinence (AI) and vaginal atrophy (VVA), who did not respond to traditional treatments such as pelvic floor exercises or hormone therapy, underwent three sessions of laser treatment using RenovaLase (SP Dynamis; Fotona d.o.o., Ljubljana, Slovenia), which employs non-ablative Erbium:YAG and Neodymium:YAG lasers. Significant improvements were observed in the VVA symptoms, with AI being resolved. The Vaginal Health Index Score increased from 7 points at the initial assessment to 18 points at 12 months after treatment. Similarly, the Cleveland Clinic Florida Fecal Incontinence Score and St. Mark's Incontinence Score, initially at 4 points each, improved to 0 points, indicating resolution of incontinence symptoms. MRI results demonstrated vascular enhancement and growth in the anal sphincter, with the thickness of the internal anal sphincter slightly increasing from initial measurements to a maximum of 0.36 cm, and improvements in resting and squeeze pressures from 42 mmHg to 110 mmHg, respectively. These findings underscore the effectiveness of RenovaLase® laser treatment for VVA and AI symptoms, offering a novel option for pelvic floor health management in postmenopausal women, especially those resistant to the use of artificial devices for anal improvement. In the environment of hormonal decline after menopause, the atrophy of pelvic vessels leads to reduced blood flow. This situation, where a noticeable lack of blood flow occurs during pretreatment of the pelvic vessels, is addressed by laser treatment. This phenomenon has been named "re-canalization." This case suggests the potential of this therapy as an alternative for patients resistant to conventional methods involving the insertion of devices into the anus to improve fecal incontinence. Further research is needed to explore its potential benefits.

Neodymium Laser Treatment for Overactive Bladder and Vulvodynia in Mayer-Rokitansky-Küster-Hauser Syndrome Patient: A Case Report.

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a condition that affects a small proportion of female individuals at birth, resulting in the absence or underdevelopment of reproductive organs. However, this case report introduces overactive bladder (OAB) and vulvodynia, conditions that have not been previously reported in MRKH patients. The 36-year-old patient began developing breast tissue around the age of 12 but never experienced menstruation. Simultaneously, she started experiencing discomfort in the genital region and frequent urination. These symptoms gradually worsened, making it difficult for her to continue her education, and initially, she was misdiagnosed with a developmental disorder. Typically, the general understanding of MRKH syndrome has focused on reproductive anomalies, but this case underscores its diversity. Diagnostic assessments, including ultrasound, MRI, and various tests, revealed that the patient's severe genital discomfort and urinary symptoms were improved through a specialized Neodymium YAG laser therapy named "PIANO mode," resulting in significant symptom relief and improved quality of life. This report emphasizes the importance of comprehensive and individualized approaches to managing MRKH syndrome. It aims to raise awareness that MRKH syndrome, while often associated with reproductive abnormalities, can also involve related symptoms like OAB and vulvodynia, which can significantly impact daily life.

The impact of menopause and serum DHEA-S level on the severity of Covid-19.

OBJECTIVES: We aimed to demonstrate the difference between premenopausal and postmenopausal women in respect of the clinical course and outcomes of Covid-19. We investigated the epidemiological and hormonal factors which influence the severity of the disease. STUDY DESIGN: This observational cross-sectional study included the female patients admitted to a Covid-19 outpatient clinic between July 2020 and June 2021 and diagnosed with a positive polymerase chain reaction test. Blood samples were obtained to determine the serum levels of follicle stimulating hormone, luteinizing hormone, estradiol, total testosterone and dehydroepiandrosterone sulfate. MAIN OUTCOME MEASURE: Our primary outcome was the poor clinical course of the disease in postmenopausal women. Our secondary outcome was the contribution of hormonal status to the clinical course of the disease. RESULTS: Our cohort consisted of 253 female patients (85 with mild, 125 with moderate and 43 with severe disease; 101 at the premenopausal and 152 at the postmenopausal stage). There was a statistically significant difference between the patients in different severity groups regarding clinical data and serum levels of luteinizing hormone, follicle stimulating hormone, estradiol and dehydroepiandrosterone sulfate. Being one year younger decreased the odds of having severe Covid-19 0.338-fold relative to the group with mild disease. A decrease in the serum dehydroepiandrosterone sulfate level was associated with a 2.604-fold increase in the odds of having severe Covid-19 relative to the group with mild disease. Being postmenopausal increased the odds of having severe disease compared with mild disease by 2.687-fold. CONCLUSIONS: The prognosis of Covid-19 is more favorable in premenopausal women compared with postmenopausal women. Age, postmenopausal status and serum levels of dehydroepiandrosterone sulfate are important predictors of the severity of Covid-19 for women.

A novel objective evaluation method, shear wave elastography, in the treatment of atrophic vaginitis by nonablative intravaginal Er:YAG laser, a randomized-sham controlled pilot study.

OBJECTIVE: The aim of the study was to investigate the effectiveness of intravaginal Er:YAG laser for treating atrophic vaginitis in postmenopausal women utilizing shear wave elastography. METHODS: In this prospective randomized sham-controlled double-blind pilot study, 20 participants were included (laser group [n = 12] / sham-control group [n = 8]). A nonablative (Smooth mode) Er:YAG laser with a wavelength of 2,940 nm was used. Objective evaluation of laser treatment efficacy was conducted using a special ultrasonic technique: shear wave elastography. Ultrasonic velocity measurements were taken from the anterior and posterior vaginal walls. Mean elasticity (E mean ) was expressed in kilopascals (kPa). Additional outcome parameters were vaginal pH, Vaginal Health Index (VHI), Female Sexual Function Index (FSFI), and visual analog scale (VAS) scores for dyspareunia. RESULTS: Baseline clinical characteristics, vaginal pH, VHI, VAS and FSFI scores, and E mean values were comparable between the laser and sham-control groups. Statistically significant differences were observed in the final E mean values of the anterior vaginal wall (13.1 ± 6.3 vs 20.0 ± 3.3 kPA, P = 0.01) and posterior vaginal wall (12.7 ± 10.3 vs 19.4 ± 6.9 kPA, P = 0.04) between the laser and sham-control group. Despite comparable baseline E mean values, significant differences in vaginal wall stiffness posttreatment indicated a notable increase in tissue elasticity following laser treatment. Statistically significant differences were also observed in final vaginal pH values, VHI, VAS scores, and FSFI score improvement in favor of laser treatment. CONCLUSIONS: Shear wave elastography may be considered as a reliable and objective technique for evaluating the efficacy of Er:YAG laser treatment in women with atrophic vaginitis. However, additional studies with larger sample sizes are necessary to establish conclusive evidence.

EMAS position statement: Thyroid disease and menopause.

INTRODUCTION: Thyroid diseases are common in women in their late reproductive years; therefore, thyroid disease and menopause may co-exist. Both conditions may present with a wide range of symptoms, leading to diagnostic challenges and delayed diagnosis. Aim To construct the first European Menopause and Andropause Society (EMAS) statement on thyroid diseases and menopause. MATERIALS AND METHODS: Literature review and consensus of expert opinion (EMAS executive board members/experts on menopause and thyroid disease). SUMMARY RECOMMENDATIONS: This position paper highlights the diagnostic and therapeutic dilemmas in managing women with thyroid disease during the menopausal transition, aiming to increase healthcare professionals' awareness of thyroid disorders and menopause-related symptoms. Clinical decisions regarding the treatment of both conditions should be made with caution and attention to the specific characteristics of this age group while adopting a personalized patient approach. The latter must include the family history, involvement of the woman in the decision-making, and respect for her preferences, to achieve overall well-being.

EMAS position statement: Testosterone replacement therapy in older men.

INTRODUCTION: Late-onset hypogonadism is the clinical entity characterised by low testosterone concentrations associated with clinical symptoms in the absence of organic disease in ageing men. It has been associated with metabolic syndrome, reduced bone mineral density, and increased cardiovascular morbidity and mortality risk. Although testosterone replacement therapy (TRT) reverses most of these conditions in young hypogonadal men, the risk/benefit ratio of TRT in older men is debatable. AIM: To update the 2015 EMAS statement on TRT in older men with new research on late-onset hypogonadism and TRT. MATERIALS AND METHODS: Literature review and consensus of expert opinion. SUMMARY RECOMMENDATIONS: TRT should be offered only to symptomatic older men with confirmed low testosterone concentrations after explaining the uncertainties regarding the long-term safety of this treatment. TRT may be offered to men with severe hypogonadism and erectile dysfunction to improve sexual desire, erectile, and orgasmic function. It should also be considered in hypogonadal men with severe insulin resistance or pre-diabetes mellitus. TRT may also be considered, in combination with proven treatment strategies, for osteoporosis, or for selected patients with persistent mild depressive symptoms and/or low self-perceived quality of life, combined with standard medical care for each condition. TRT is contraindicated in hypogonadal men actively seeking fertility treatment. Due to a lack of data, TRT should not be routinely used in older men to improve exercise capacity/physical function, improve cognitive function, or prevent cognitive decline. TRT must be avoided in older, frail men with known breast cancer or untreated prostate cancer and all men who have had myocardial infarction or stroke within the last four months, and those with severe or decompensated heart failure. The quality of evidence regarding patients with previous prostate cancer or cardiovascular disease is too low to draw definitive conclusions. Any limits on duration of use are arbitrary, and treatment should continue for as long as the man feels the benefits outweigh the risks for him, and decisions must be made on an individual basis. Withdrawal should be considered when hypogonadism is reversed after the resolution of underlying disorder. Short-acting transdermal preparations should be preferred for TRT initiation in older men, but injectable forms may be considered subsequently. Older men on TRT should be monitored at 3, 6, and 12 months after initiation and at least yearly thereafter, or earlier and more frequently if indicated. Evaluation should include assessment of the clinical response, and measurement of total testosterone, haematocrit, and prostate-specific antigen (PSA) concentrations. Bone density and/or quality should also be assessed. Obese and overweight patients should be encouraged to undergo lifestyle modifications, including exercise and weight loss, to increase endogenous testosterone.

Predictive factors for the efficacy of Er:YAG laser treatment of urinary incontinence.

OBJECTIVES: To determine the efficacy and predictive factors for the success of Er:YAG laser treatment in patients with urinary incontinence (UI). METHODS: Eighty-two patients with UI were treated by Er:YAG laser in this cohort study. The patients were evaluated by ICIQ-SF and KHQ-UI before and after the procedure. Improvement was categorized as: none (0-25%), mild (26-50%), moderate (51-75%), or high (76-100%). The duration of the treatment effect was evaluated at follow-up in relation to maximum improvement time (MIT) and total improvement time (TIT). RESULTS: Forty-two patients were determined to have SUI and 40 patients MUI. The mean ISIQ-SF and KHQ-UI scores significantly improved after the procedure (p<0.0001). The SUI patients responded to the laser treatment significantly better (p<0.008). Younger women had significantly better results (p<0.008), while premenopausal women (p<0.032) and women in the early postmenopausal years (p<0.032) also saw a positive response to the Er:YAG laser treatment. Women with a lower BMI had greater improvement (p<0.011). The total laser energy expenditure during the sessions may also be a predictive parameter for the success of Er:YAG laser treatment of UI (p = 0.059). MIT and TIT were significantly longer among the patients in the high-improvement group. CONCLUSION: Er:YAG laser treatment of the symptoms of UI, especially SUI, is more efficacious and of longer duration for younger, premenopausal or early postmenopausal women with normal BMI.

Er:YAG laser treatment of urinary incontinence after failed TOT/TVT procedures.

OBJECTIVE: To determine if the Er:YAG laser can improve the symptoms of SUI patients after previously failed TOT/TVT procedures. STUDY DESIGN: This retrospective study includes the data of patients who were recruited from two different out-patient clinics of Obstetrics and Gynecology Department. 25 women with persistent SUI after failed TOT/TVT operations and 25 women who previously did not receive either any type of surgical treatment procedure or non-invasive treatment modalities for SUI. Er:YAG laser with 2940 nm was used in the treatment procedure for SUI setting. The patients were evaluated on the basis of ICIQ-SF before and after the procedure. The severity of SUI symptoms was graded. According to the differences in the ICIQ-SF between before and after the procedure, the percentage of improvement was graded as good responders (≥50 %) or poor responders (<50 %).The duration of the treatment effect was evaluated in follow-ups with relation to maximum improvement time (MIT) and total improvement time (TIT). RESULTS: The SUI patients who previously had failed TOT/TVT operations, had significantly higher initial ICIQ-SF score (p = 0.013). Non-ablative Er:YAG laser treatment significantly and similarly improved the severity of SUI symptoms in both groups (p = 0.000 for failed TOT/TVT group and p = 0.001 for non-TOT/TVT group, respectively). The women who were good responders, were younger (p = 0.012) and had less number of years in menopause (p = 0.011). The effect of Er:YAG laser treatment lasted longer among the SUI women in the good responders group (p = 0.000 for MIT and p = 0.000 for TIT, respectively). CONCLUSIONS: Non-ablative Er:YAG smooth mode laser is an alternative choice of treatment for the SUI patients who previously had failed TOT/TVT procedures. Its effect lasts longer especially in younger and early postmenopausal women.

Effect of different hormonal therapies on thyroid function in surgical menopause: short-term results.

OBJECTIVE: To determine the effects of different hormone replacement therapy (HRT) regimens on thyroid function in surgical menopause. STUDY DESIGN: In a randomized, controlled study, 59 euthyroid women with surgical menopause were randomized to an estrogen-only (n=20), tibolone (n=20) or calcium-only (n=19) group. On the 5th postoperative day and 4th and 12th weeks, serum E2, TSH, free T3 and free T4 levels were determined. RESULTS: Although the initial and week 4 serum E2, TSH, free T3 and free T4 levels were comparable, the week 12 serum E2 and TSH levels were different between the subjects on estrogen therapy and those receiving tibolone or calcium only (p=0.008 and 0.000, respectively). Serum E2 levels were higher and TSH levels lower in subjects receiving estrogen. Moreover, serum TSH levels correlated negatively with serum E2 levels in the 12th week of estrogen use (r=-0.354, p=0.006). TSH increased in the tibolone group as compared to the estrogen group but was still lower than in the calcium-only group; however, the differences were not statistically significant. CONCLUSION: Irrespective of different regimens, HRT does not have an important short-term effect on thyroid function in women with surgical menopause.

Adjusted leptin level (ALL) is a predictor for hyperemesis gravidarum.

OBJECTIVE: To compare the maternal serum leptin level according to the gestational week and to assess the relationship between the adjusted serum leptin level and thyroid hormones. In order to obtain this objective a new parameter is developed: adjusted leptin level (ALL: maternal serum leptin level/gestational week). STUDY DESIGN: A prospective study was carried out at the early prenatal care unit, SSK Ankara Women's Health and Teaching Hospital. Fifty-four women with hyperemesis gravidarum (HG) and 42 pregnant women without HG as a control group were included to the study. The groups were compared for age, parity, body mass index, fasting serum TSH, free T3, free T4 and leptin levels. A new parameter; ALL was also calculated in each case. RESULTS: Gestational age and body mass index (BMI) were found significantly lower in the HG group than in the control group (p=0.001). ALL was significantly high in the HG group (p=0.009). Serum TSH, free T3, free T4 levels were significantly different in the HG group than in the control group (p=0.003, 0.013, 0.012, respectively). A significant positive correlation was found between ALL and BMI in the HG group (r=0.449 p=0.001). The maternal leptin level was also positively correlated with BMI in the HG group (r=0.313 p=0.025). CONCLUSION: Etiology of the hyperemesis gravidarum is multifactorial. However we can postulate the adjusted leptin level is a good predictor for hyperemesis gravidarum.

Tibolone and breast cancer.

Tibolone is a relatively new drug for postmenopausal women, which is structurally related to 19-nortestosterone derivatives and exhibits weak oestrogenic, progestogenic and androgenic activities. The effect of tibolone on breast tissue is still obscure. In vitro studies have shown conflicting results regarding the effects of tibolone on breast cells. On the other hand, although epidemiological studies show an increase in the risk of breast cancer among women treated with tibolone, accumulation of data obtained from radiological studies presents promising results. However, the safety of tibolone with regard to breast tissue needs to be investigated further, especially through well-designed, large-scale, randomised-controlled trials.

EMAS position statement: Non-hormonal management of menopausal vasomotor symptoms.

AIM: To review non-hormonal therapy options for menopausal vasomotor symptoms. The current EMAS position paper aims to provide to provide guidance for managing peri- and postmenopausal women who cannot or do not wish to take menopausal hormone therapy (MHT). MATERIAL AND METHODS: Literature review and consensus of expert opinion. RESULTS: Non-hormonal management of menopausal symptoms includes lifestyle modifications, diet and food supplements, non-hormonal medications and application of behavioral and alternative medicine therapies. There is insufficient or conflicting evidence to suggest that exercise, supplements or a diet rich in phytoestrogens are effective for vasomotor menopausal symptoms. Selective serotonin-reuptake inhibitors (SSRIs), serotonin norepinephrine-reuptake inhibitors (SNRIs) and gabapentin could be proposed as alternatives to MHT for menopausal symptoms, mainly hot flushes. Behavioral therapies and alternative medicine interventions have been tried, but the available evidence is still limited. CONCLUSIONS: A number of interventions for non-hormonal management of menopausal vasomotor symptoms are now available. For women who cannot or do not wish to take estrogens, non-hormonal management is now a realistic option.

EMAS position statement: The ten point guide to the integral management of menopausal health.

With increased longevity and more women becoming centenarians, management of the menopause and postreproductive health is of growing importance as it has the potential to help promote health over several decades. Women have individual needs and the approach needs to be personalised. The position statement provides a short integral guide for all those involved in menopausal health. It covers diagnosis, screening for diseases in later life, treatment and follow-up.

EMAS position statement: management of uterine fibroids.

INTRODUCTION: Uterine fibroids (also termed leiomyomas or myomas) are the most common tumors of the female reproductive tract. AIM: The aim of this position statement is to provide and critically appraise evidence on the management of women with uterine fibroids. METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Many uterine fibroids are asymptomatic and require no intervention, although it is advisable to follow up patients to document stability in size and growth. Fibroid-associated symptoms include heavy menstrual bleeding and pain or pelvic discomfort. The association between infertility and fibroids increases with age. Fibroids do not increase the risk of malignant uterine disease and leiomyosarcomas are extremely rare (less than one in 1000). It is unknown at present whether leiomyosarcoma represents de novo growth or malignant transformation from benign uterine fibroids. Treatment options for symptomatic fibroids include pharmacologic, surgical and radiologically guided interventions. The range of medical treatments allows flexible management of fibroid-related symptoms; the options include tranexamic acid, non-steroidal anti-inflammatory drugs, contraceptive steroids, gonadotropin-releasing hormone analogs, antiprogesterone, and selective progesterone receptor modulators. However, these medical options do not remove the tumors and symptoms may return when treatment is stopped. Surgical and radiologically guided procedures may be tailored to age, general health, and individual patient wishes. Hysterectomy is the most effective treatment, although in some cases myomectomy may be sufficient to control symptoms. Alternatives to surgery include uterine artery embolization, myolysis and ablation by high-intensity focused ultrasound (guided with magnetic resonance imaging or ultrasound). The choice of treatment depends on fibroid size, the underlying symptoms and their severity and the woman's desire for subsequent fertility and pregnancy, as well as efficacy and need for repeated interventions.

EMAS position statement: individualized breast cancer screening versus population-based mammography screening programmes.

INTRODUCTION: Breast cancer is the most prevalent cancer in women, with slightly more than ten percent developing the disease in Western countries. Mammography screening is a well established method to detect breast cancer. AIMS: The aim of the position statement is to review critically the advantages and shortcomings of population based mammography screening. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSION: Mammography screening programmes vary worldwide. Thus there are differences in the age at which screening is started and stopped and in the screening interval. Furthermore differences in screening quality (such as equipment, technique, resolution, single or double reading, recall rates) result in a sensitivity varying from 70% to 94% between studies. Reporting results of screening is subject to different types of bias such as overdiagnosis. Thus because of the limitations of population-based mammography screening programmes an algorithm for individualized screening is proposed.

EMAS position statement: Fertility preservation.

INTRODUCTION: The increasing incidence of malignant diseases that often require gonadotoxic treatment and the tendency to become a parent later in life result in an increased need for fertility preservation. AIMS: The aim of this position statement is to provide and critically appraise evidence on available options for fertility preservation in both pre-pubertal and post-pubertal men and women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Fertility preservation should be a priority when treating children or adults of reproductive age with agents that may have hazardous effects on the reproductive system. Gonadotoxicity should be kept at a minimum. If gonadotoxic treatment has to be used, methods of fertility preservation should be discussed, as early as possible.

EMAS position statement: The management of postmenopausal women with vertebral osteoporotic fracture.

INTRODUCTION: Osteoporotic vertebral fractures are associated with significant morbidity, excess mortality as well as health and social service expenditure. Additionally, women with a prevalent osteoporotic vertebral fracture have a high risk of experiencing a further one within one year. It is therefore important for the physician to use a diagnostic and therapeutic algorithm for early detection and effective treatment of vertebral fractures. AIMS: The aim of this position statement is to provide and critically appraise evidence on the management of women with a vertebral osteoporotic fracture. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: The management of women with osteoporotic vertebral fractures includes measures to reduce pain providing early mobility, to support the affected spine ensuring fracture healing, as well as starting treatment for osteoporosis itself. Any other underlying pathology should be sought and treated. Early detection and treatment is essential as there is an increased risk of further fractures in patients with vertebral fractures. Treatment will depend on the underlying causes of bone loss, efficacy in any particular situation, cost and patient preference.