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.

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.

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.

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.

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: 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: 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 clinical guide: assessment of the endometrium in peri and postmenopausal women.

INTRODUCTION: Invasive as well as non-invasive methods are available for assessment of the endometrium. AIMS: The purpose of this clinical guide is to provide evidence-based advice on endometrial assessment in peri and postmenopausal women. MATERIAL AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Presuming speculum examination and cervical cytology are assessed, transvaginal ultrasound should be undertaken initially as it is non-invasive and will not only measure endometrial thickness, but will also detect other pelvic pathology such as leiomyomas and ovarian tumours. The main indication for invasive methods is to obtain endometrial tissue to diagnose or exclude the presence of endometrial cancer or pre-malignancies. Biopsy is mainly undertaken as an outpatient procedure, but sampling is 'blind'. Hysteroscopy is used when focal lesions affecting the uterine cavity are suspected such as endometrial polyps or sub-mucous fibroids. None of the available methods are perfect. Ultrasound evaluation is dependent on the experience of the examiner, the equipment and the quality of visualization. Hysteroscopy too is dependent on the examiner and fibroids may obstruct visualization. Blind endometrial biopsy procedures often miss focal lesions. Thus re-examination is necessary when symptoms persist and no explanation for these has been identified. This clinical guide will evaluate the different methods of endometrial assessment, their indications and limitations. Guidance is also given about dealing with inconclusive investigations and persistent symptoms.

EMAS clinical guide: vulvar lichen sclerosus in peri and postmenopausal women.

INTRODUCTION: Vulvar lichen sclerosus (LS) is a chronic inflammatory disease which affects genital labial, perineal and perianal areas, producing significant discomfort and psychological distress. However there may be diagnostic delay because of late presentation and lack of recognition of symptoms. AIMS: The purpose of this clinical guide is to provide advice on early recognition and treatment. MATERIAL AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: The etiology of LS in peri and postmenopausal women is unknown, although autoimmune, genetic and infectious factors have been implicated. Definitive diagnosis of non-malignant disorders depends on the histology of biopsied tissue. LS associated with cellular atypia should be classified as intraepithelial neoplasia. Topical corticosteroids are the most effective treatment, although prolonged treatment may be associated with dermal atrophy. Topical calcineurin inhibitors, such as tacrolimus or pimecrolimus, may be a safe and effective alternative treatment without risk of corticosteroid-related vulvar atrophy since they do not affect collagen synthesis. LS recurrences are frequent, and can lead to significant physical discomfort and emotional distress that affect mood and sexual relationships. Anatomical changes may require surgical management.

EMAS clinical guide: selective estrogen receptor modulators for postmenopausal osteoporosis.

Osteoporosis and the resulting fractures are major public health issues as the world population is ageing. Various therapies such as bisphosphonates, strontium ranelate and more recently denosumab are available. This clinical guide provides the evidence for the clinical use of selective estrogen modulators (SERMs) in the management of osteoporosis in postmenopausal women.

EMAS position statement: Vitamin D and postmenopausal health.

INTRODUCTION: There is emerging evidence on the widespread tissue effects of vitamin D. AIMS: To formulate a position statement on the role of vitamin D in postmenopausal women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Epidemiological and prospective studies have related vitamin D deficiency with not only osteoporosis but also cardiovascular disease, diabetes, cancer, infections and neurodegenerative disease. However the evidence is robust for skeletal but not nonskeletal outcomes where data from large prospective studies are lacking. The major natural source of vitamin D is cutaneous synthesis through exposure to sunlight with a small amount from the diet in animal-based foods such as fatty fish, eggs and milk. Vitamin D status is determined by measuring serum 25-hydroxyvitamin D [25(OH)D] levels. Optimal serum 25(OH)D levels are in the region of 30-90 ng/mL (75-225 nmol/L) though there is no international consensus. Levels vary according to time of the year (lower in the winter), latitude, altitude, air pollution, skin pigmentation, use of sunscreens and clothing coverage. Risk factors for low serum 25(OH)D levels include: obesity, malabsorption syndromes, medication use (e.g. anticonvulsants, antiretrovirals), skin aging, low sun exposure and those in residential care. Fortified foods do not necessarily provide sufficient amounts of vitamin D. Regular sunlight exposure (without sunscreens) for 15 min, 3-4 times a week, in the middle of the day in summer generate healthy levels. The recommended daily allowance is 600 IU/day increasing to 800 IU/day in those aged 71 years and older. Supplementation can be undertaken with either vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol) with monitoring depending on the dose used and the presence of concomitant medical conditions such as renal disease.

EMAS position statement: Managing menopausal women with a personal or family history of VTE.

INTRODUCTION: Venous thromboembolism (VTE), including deep venous thrombosis (DVT) and pulmonary embolism (PE), is a serious cardiovascular event whose incidence rises with increasing age. AIMS: To formulate a position statement on the management of the menopause in women with a personal or family history of VTE. MATERIAL AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Randomized controlled trials have shown an increased risk of VTE in oral hormone therapy (HT) users. There are no randomized trial data on the effect of transdermal estrogen on VTE. Recent observational studies and meta-analyses suggest that transdermal estrogen does not increase VTE risk. These clinical observations are supported by experimental data showing that transdermal estrogen has a minimal effect on hepatic metabolism of hemostatic proteins as the portal circulation is bypassed. A personal or family history of VTE, especially in individuals with a prothrombotic mutation, is a strong contraindication to oral HT but transdermal estrogen can be considered after careful individual evaluation of the benefits and risks. Transdermal estrogen should be also the first choice in overweight/obese women requiring HT. Observational studies suggest that micronized progesterone and dydrogesterone might have a better risk profile than other progestins with regard to VTE risk. Although these findings should be confirmed by randomized clinical trials, they strongly suggest that both the route of estrogen administration and the type of progestin may be important determinants of the overall benefit-risk profile of HT.

EMAS position statement: Managing the menopause in the context of coronary heart disease.

INTRODUCTION: Cardiovascular disease (CVD) including coronary heart disease (CHD) and stroke is the most common cause of female death. Premenopausal CHD is very rare but when women enter the menopause the incidence of CHD increases markedly. CHD presents 10 years later in women than in men. The reason is still unclear but the protective effects of estrogens have been suggested. AIMS: To formulate a position statement on the management of menopause women in the context of coronary heart disease. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Based on long term randomized placebo-controlled studies hormone therapy (HT) is not recommended for the primary or secondary prevention of CHD in postmenopausal women. In most countries the only indication for HT is the treatment of menopausal symptoms. Women with known CHD or with many coronary risk factors seeking HT because of troublesome climacteric symptoms should be evaluated for their individual baseline risk of developing breast cancer, venous thromboembolism and CHD recurrence. The same applies to non hormone therapy-based treatments where long term clinical studies are lacking. Risks should be weighed against expected benefit from symptom relief and improved quality of life. The lowest effective estrogen dose should be used during the shortest possible time. Transdermal administration is preferred if risk factors for VTE exist. Different progestogens might differ in their cardiovascular effects. Observational studies suggest that micronized progesterone or dydrogesterone may have a better risk profile than other progestogens with regard to thrombotic risk.

EMAS position statement: Bone densitometry screening for osteoporosis.

INTRODUCTION: Osteoporosis and its consequent fractures is a major public health problem. AIM: To formulate a position statement on the use of bone densitometry in screening postmenopausal women for osteoporosis and in their management. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Bone densitometry has an important role in screening postmenopausal women for osteoporosis. For higher sensitivity and specificity, there may be a stronger case for screening in later life, depending on the extent to which risk factors add to the value of bone mineral density tests.

EMAS position statement: managing obese postmenopausal women.

INTRODUCTION: Obesity is a public health problem, with overweight individuals representing approximately 20% of the adult world population. Postmenopausal status is associated with higher prevalence of obesity, as 44% of postmenopausal women are overweight, among whom 23% are obese. Obesity often co-exists with other diseases, the most important being diabetes mellitus, dyslipidemia and hypertension. Furthermore, obesity increases the risk of gynecologic cancer, cardiovascular disease, venous thromboembolism, osteoarthritis and chronic back pain. AIM: To formulate a position statement on the management of the menopause in obese women. MATERIALS AND METHODS: Literature review and consensus of expert opinion. RESULTS AND CONCLUSIONS: Obese women seeking hormone therapy should be evaluated for their individual baseline risk of developing breast cancer, cardiovascular disease and venous thromboembolism. These risks should be weighed against expected benefit from symptom relief, improved quality of life and osteoporosis prevention. The lowest effective estrogen dose should be used (CEE 0.300-0.400 mg or estradiol 0.5-1 mg orally daily or 25-50 microg estradiol transdermally). With regard to progestogens, although no RCT data exist, there are observational studies showing that micronized progesterone or dydrogesterone may have a better risk profile with respect to breast cancer risk. There are no RCT data comparing various progestogens with regard to VTE risk. There are observational data, however, suggesting that micronized progesterone or pregnane derivatives may be associated with a lower VTE risk in postmenopausal women taking HT compared to nonpregnane derivatives. There is a rationale in suggesting the use of transdermal HT in obese women, since this route of administration has been associated with a lesser risk of venous thromboembolism than oral therapy.

Thin endometrium in assisted reproductive technology.

PURPOSE OF REVIEW: To review the etiology, diagnosis and clinical importance of thin endometrium during assisted reproductive technology cycles and to find out better ways to deal with it. RECENT FINDINGS: Precise and specific endometrial maturational development is crucial in allowing implantation following assisted reproduction. As endometrial biopsy is invasive and hormonal milieu assessment inaccurate, the need to evaluate endometrial development encouraged the use of high-resolution ultrasonography as an alternative non-invasive method of assessment for uterine receptivity. Ultrasonographic endometrial thickness measurement, endometrial pattern investigation, endometrial volume computation, uterine and subendometrial blood flow analysis by Doppler sonography are just some of the methods that we can utilize to have an idea of uterine receptivity and consequently to better predict pregnancy outcome following assisted reproductive technology cycles. There is a lot of debate on the administration of low-dose aspirin, estrogen, vaginal sildenafil citrate, pentoxifylline, vitamin E, and gonadotropin-releasing hormone agonist for the management of thin endometrium with an aim to increase the pregnancy and implantation rates in assisted reproductive technology cycles. SUMMARY: Various recent modalities proposed for the treatment of thin endometrium seem to be useless and inefficient from an evidence-based medicine point of view. At the moment, evaluation of endometrium using different ultrasonographic markers seems to be superior to all those therapies.

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.

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.

Is laparoscopy necessary before assisted reproductive technology?

PURPOSE OF REVIEW: Laparoscopy is widely used during infertility work-up, although it is sometimes unnecessary. This review highlights when laparoscopic intervention should be used in women undergoing assisted reproductive technology cycles. RECENT FINDINGS: There is no evidence for an increase in pregnancy rates in assisted reproductive technology cycles following surgical treatment of pelvic adhesions or endometriosis with laparoscopy. If the patient has bilateral visible hydrosalpinges, laparoscopy may be an option for evaluation of the tubes and treatment with salpingectomy in order to enhance the chance of pregnancy before commencing an assisted reproductive technology cycle. Laparoscopic ovarian drilling before assisted reproductive technology may be considered a therapeutic option in polycystic ovary disease patients who previously had severe ovarian hyperstimulation syndrome. Finally, laparoscopy may be useful in replacing the transposed ovaries to their original sites in the pelvic cavity in previously treated cancer patients so that monitoring of the controlled ovarian hyperstimulation and the oocyte aspiration would be much easier during the assisted reproductive technology cycles. SUMMARY: Laparoscopy should be considered before assisted reproductive technology cycles if the procedure diagnoses and treats a pelvic pathology at the same time and if laparoscopic intervention increases the chance of pregnancy following these cycles.