Preoperative topical estrogen application in the management of hypospadias: a systematic review.

Local estrogen therapy has been explored as an alternative to conventional testosterone therapy in children requiring urethroplasty for hypospadias. Our objective is to evaluate if preoperative estrogen stimulation reduces post-urethroplasty complications and enhances penile dimensions. A systematic search was conducted on various databases, selecting only randomized controlled trials (RCTs) that tested estrogen on hypospadias patients under 18 years. Articles underwent sorting following PRISMA guidelines and bias risk was assessed using the JBI clinical appraisal tool for RCTs. Out of 607 screened records, 10 underwent full-text review, and 4 randomized controlled trials (RCTs) were selected for analysis. The total patient cohort across studies was 387 with 174 in the estrogen group. All studies utilized topical estrogen, but in different formulations and timings. Prudence is necessary for interpreting results due to variations in formulation, timing, and hypospadias type across studies. Limited by a small number of studies and outcome presentation non-uniformity, the review suggests no change in penile dimensions or postoperative complications with topical estrogen. Further research is needed to explore wound-healing properties of estrogen in hypospadias through animal and human studies.Registration and protocol: Registered in Prospero CRD42024502183.

Association between serum estradiol and cardiovascular health among transgender adults using gender-affirming estrogen therapy.

Gender-affirming estrogen therapy (GAET) is commonly used for feminization in transgender and nonbinary (TNB) individuals, yet the optimal rate of change (ROC) in estradiol levels for cardiovascular health is unclear. We examined the association between serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Cochrane Central Register of Controlled Trials, EMBASE, MEDLINE, and Web of Science were systematically searched (inception-April 2023) for original articles reporting serum estradiol levels and cardiovascular-related mortality, adverse events, and risk factors in TNB adults using GAET. Data extraction was completed in duplicate following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Stratified random effect meta-analyses using serum estradiol ROC (serum estradiolbaseline - serum estradiolfollow-up/study duration) was used to assess longitudinal studies (low, 0 < ROC ≤ 1 pg/mL/mo; moderate, 1 < ROC ≤ 3 pg/mL/mo; high, ROC ≥ 3 pg/mL/mo). Thirty-five studies (13 cross-sectional, 19 cohort, and 3 trials) were included. Two studies collectively reported 50 cardiovascular-related deaths, and four collectively reported 23 adverse cardiovascular events. Nineteen studies reporting cardiovascular risk factors were meta-analyzed by ROC stratum (low = 5; moderate = 6; high = 8), demonstrating an association between moderate [0.40, 95% confidence interval (CI): 0.22, 0.59 kg/m2, I2 = 28.2%] and high (0.46, 95% CI: 0.15, 0.78 kg/m2; I2 = 0.0%) serum estradiol ROC and increased body mass index. High (-6.67, 95% CI: -10.65, -2.68 mg/dL; I2 = 0.0%) serum estradiol ROC was associated with decreased low-density lipoproteins. Low (-7.05, 95% CI: -10.40, -3.70 mmHg; I2 = 0.0%) and moderate (-3.69, 95% CI: -4.93, -2.45 mmHg; I2 = 0.0%) serum estradiol ROCs were associated with decreases in systolic blood pressure. In TNB adults using GAET, serum estradiol ROC may influence cardiovascular risk factors, which may have implications for clinical cardiovascular outcomes.NEW & NOTEWORTHY In this systematic review and meta-analysis of 35 studies involving 7,745 participants, high rates of serum estradiol change were associated with small increases in body mass index. Moderate to high rates of change were associated with decreases in low-density lipoprotein. Low rates of change were associated with small decreases in systolic blood pressure. Rate of serum estradiol change in adults using gender-affirming estrogen therapy may influence cardiovascular risk factors, though further research is warranted.

Genitourinary Syndrome of Menopause: A Narrative Review Focusing on Its Effects on the Sexual Health and Quality of Life of Women.

Genitourinary syndrome of menopause (GSM) is a progressive condition due to a hypoestrogenic state affecting perimenopausal and menopausal women. GSM was previously known as urogenital syndrome, vulvovaginal atrophy, or atrophic vaginitis. The term vulvovaginal atrophy did not encompass the symptoms of the urinary tract like incontinence, urgency, and discomfort, or allude that it is due to a hypoestrogenic state. Although a significant segment of the population is affected by GSM, it is very sparsely studied, detected, and treated. GSM affects the quality of life and sexual health of most menopausal women suffering from it. Only a few healthcare providers ask about the symptoms of GSM and a tiny percentage of women seek consultation for it. This may be because they are either embarrassed or believe it to be a part of the natural process of aging. As the life expectancy of women has increased in general, the prevalence of GSM has also risen, while it still remains underdiagnosed and untreated. Properly educating women so that they can seek consultation regarding symptoms of GSM, and training healthcare professionals about communicating with the patient, as well as correctly identifying, diagnosing, and managing the patient are all important to overcome this communication barrier. Once we cross the barrier of diagnosing patients with GSM, we still have to manage the patients with tailor-made prescriptions according to the severity of the symptoms and their preferences. While there are various treatment options, the most effective one is low-dose topical estrogen therapy. In this review, we intend to explore the existing knowledge about GSM and its effect on the quality of life and sexual health of women along with the treatment options for managing and reversing the effects of GSM.

The Role of Estrogen Therapy as a Protective Factor for Alzheimer's Disease and Dementia in Postmenopausal Women: A Comprehensive Review of the Literature.

The complete cessation of menstruation for 12 months with associated vasomotor symptoms is termed menopause. Apart from playing a role in reproduction, estrogen significantly affects the central nervous system (CNS). Population-based studies highlighted a substantial difference in the prevalence of dementia between men and women, with Alzheimer-associated dementia being more prevalent in women, indicating that estrogen deficiency might be a risk factor for neurodegenerative diseases. Patients with dementia experience a progressive decline in neurocognitive function, beginning with short-term memory loss that progresses to long-term memory loss and the inability to perform everyday activities, leading ultimately to death. There is currently no cure for dementia, so preventing or slowing the disease's progression is paramount. Accordingly, researchers have widely studied the role of estrogen as a neuroprotective agent. Estrogen prevents dementia by augmenting Hippocampal and prefrontal cortex function, reducing neuroinflammation, preventing degradation of estrogen receptors, decreasing oxidative damage to the brain, and increasing cholinergic and serotonergic function. According to the window phase hypothesis, estrogen's effect on preventing dementia is more pronounced if therapy is started early, during the first five years of menopause. Other studies like The Woman's Health Initiative Memory Study (WHIMS) showed unfavorable effects of estrogen on the brain. This review aims to establish an understanding of the currently available data on estrogen's effect on neurodegeneration, namely, dementia and Alzheimer's disease.

No Thromboembolic Complications After Facial Feminization Surgery in Transgender Patients Utilizing Estrogen Therapy: A Retrospective Cohort Study.

Purpose: Estrogen therapy is associated with an increased risk of venous thromboembolism (VTE). A large proportion of transfeminine patients use estrogen therapy before undergoing gender-affirming surgery. Many surgeons implement the discontinuation of hormone therapy before surgery. This study sought to evaluate the perioperative risk of VTE in transfeminine patients undergoing the procedure of facial feminization. Methods: Retrospective chart reviews were performed of all patients who underwent facial feminization by a single surgeon at an urban academic institution from 2014 to 2020. Patient characteristics including comorbidities, Caprini score, VTE chemoprophylaxis, and perioperative hormone therapy management were reviewed. The incidences of VTE during perioperative hospital stay and within 1 week and 6 months after the surgical procedure were examined. Results: There were 296 facial feminization procedures performed on 282 distinct patients who met criteria for inclusion in the study. Hormone therapy was prescribed to 83.6% of patients, 69.5% of whom reported that they held these medications before the procedure. Of those holding, 84.1% of patients reported they discontinued these medications between 2 and 4 weeks. No patients received VTE chemoprophylaxis. There were 0 VTE incidents during the patients' perioperative period up to 6 months postprocedure. Conclusion: Our findings support that transfeminine patients who use estrogen hormone therapy are at a minimal risk to experience VTE when undergoing facial feminization procedures. Future directions include evaluating the psychologic effect of discontinuing hormone therapy to help guide perioperative decision making.

Different local estrogen therapies for a tailored approach to GSM.

Local estrogen therapy (LET) is the mainstay of treatment for vaginal dryness, dyspareunia and other urogenital symptoms because it may reverse some pathophysiological mechanisms associated with decreasing endocrine function and increasing aging. Over the years, several vaginal products including different formulations (tablets, rings, capsules, pessaries, creams, gels and ovules) and molecules (estradiol [E2], estriol [E3], promestriene, conjugated equine estrogens and estrone) have been used with superimposable therapeutic results. Low-dose and ultra-low-dose LET is the gold standard due to its minimal systemic absorption, with circulating E2 levels persistently remaining in the postmenopausal range. In healthy postmenopausal women, preference among the various products is presently the main driver and dissatisfaction with LET seems high, namely because of the delayed use in those with severe symptoms of genitourinary syndrome of menopause (GSM). Specific concerns remain in high-risk populations such as breast cancer survivors (BCS), especially those under treatment with aromatase inhibitors. Based on the multitude of symptoms under the umbrella of GSM definition, which includes vulvovaginal atrophy (VVA), it is mandatory to investigate specific effects of LET on quality of life, sexual function and genitourinary conditions by conducting studies with a patient-tailored focus.

Estrogen and the Vascular Endothelium: The Unanswered Questions.

Premenopausal women have a lower incidence of cardiovascular disease (CVD) compared with their age-matched male counterparts; however, this discrepancy is abolished following the transition to menopause or during low estrogen states. This, combined with a large amount of basic and preclinical data indicating that estrogen is vasculoprotective, supports the concept that hormone therapy could improve cardiovascular health. However, clinical outcomes in individuals undergoing estrogen treatment have been highly variable, challenging the current paradigm regarding the role of estrogen in the fight against heart disease. Increased risk for CVD correlates with long-term oral contraceptive use, hormone replacement therapy in older, postmenopausal cisgender females, and gender affirmation treatment for transgender females. Vascular endothelial dysfunction serves as a nidus for the development of many cardiovascular diseases and is highly predictive of future CVD risk. Despite preclinical studies indicating that estrogen promotes a quiescent, functional endothelium, it still remains unclear why these observations do not translate to improved CVD outcomes. The goal of this review is to explore our current understanding of the effect of estrogen on the vasculature, with a focus on endothelial health. Following a discussion regarding the influence of estrogen on large and small artery function, critical knowledge gaps are identified. Finally, novel mechanisms and hypotheses are presented that may explain the lack of cardiovascular benefit in unique patient populations.

Cognitive Decline in Early and Premature Menopause.

Early and premature menopause, or premature ovarian insufficiency (POI), affects 1% of women under the age of 40 years. This paper reviews the main aspects of early and premature menopause and their impact on cognitive decline. Based on the literature, cognitive complaints are more common near menopause: a phase marked by a decrease in hormone levels, especially estrogen. A premature reduction in estrogen puts women at a higher risk for cardiovascular disease, parkinsonism, depression, osteoporosis, hypertension, weight gain, midlife diabetes, as well as cognitive disorders and dementia, such as Alzheimer's disease (AD). Experimental and epidemiological studies suggest that female sex hormones have long-lasting neuroprotective and anti-aging properties. Estrogens seem to prevent cognitive disorders arising from a cholinergic deficit in women and female animals in middle age premature menopause that affects the central nervous system (CNS) directly and indirectly, both transiently and in the long term, leads to cognitive impairment or even dementia, mainly due to the decrease in estrogen levels and comorbidity with cardiovascular risk factors, autoimmune diseases, and aging. Menopausal hormone therapy from menopause to the age of 60 years may provide a "window of opportunity" to reduce the risk of mild cognitive impairment (MCI) and AD in later life. Women with earlier menopause should be taken care of by various specialists such as gynecologists, endocrinologists, neurologists, and psychiatrists in order to maintain their mental health at the highest possible level.

The Role of ERα and ERß in Castration-Resistant Prostate Cancer and Current Therapeutic Approaches.

Castration-resistant prostate cancer, or CRPC, is an aggressive stage of prostate cancer (PCa) in which PCa cells invade nearby or other parts of the body. When a patient with PCa goes through androgen deprivation therapy (ADT) and the cancer comes back or worsens, this is called CRPC. Instead of androgen-dependent signalling, recent studies show the involvement of the estrogen pathway through the regulation of estrogen receptor alpha (ERα) and estrogen receptor beta (ERß) in CRPC development. Reduced levels of testosterone due to ADT lead to low ERß functionality in inhibiting the proliferation of PCa cells. Additionally, ERα, which possesses androgen independence, continues to promote the proliferation of PCa cells. The functions of ERα and ERß in controlling PCa progression have been studied, but further research is needed to elucidate their roles in promoting CRPC. Finding new ways to treat the disease and stop it from becoming worse will require a clear understanding of the molecular processes that can lead to CRPC. The current review summarizes the underlying processes involving ERα and ERß in developing CRPC, including castration-resistant mechanisms after ADT and available medication modification in mitigating CRPC progression, with the goal of directing future research and treatment.

Pre- versus Post-Menopausal Onset of Overactive Bladder and the Response to Vaginal Estrogen Therapy: A Prospective Study.

Background and Objectives: This study examined the utility of local estrogen therapy for improving urinary symptoms in women diagnosed with Overactive Bladder allied to the time of onset of urinary symptoms whether pre- or post-menopausal. Materials and Methods: Subject to informed consent, menopausal women diagnosed with Overactive Bladder (OAB) and Genitourinary Syndrome of Menopause (GSM) were enrolled at three urogynecological units. OAB symptoms were scored using the Global Pelvic Floor Symptoms Bother Questionnaire (GPFSBQ), with explicit attention to question number 3 that specifically addresses the presence or absence of urgency and the Patient Perception of Intensity of Urgency Scale (PPIUS). The Vaginal Health Index (VHI) was used to assess the vaginal mucosa trophism. Exclusion criteria included: Pelvic organ prolapse (POP) ≥ stage II, urinary tract infection or disease, diabetes, inflammatory diseases, use of diuretics, alcohol or drug addictions, neurological and/or psychiatric disorders, and other precluding conditions. Women were treated with local estrogens for 3 months and re-evaluated. Results: Forty-three post-menopausal women were enrolled. Of these, ten women developed OAB symptoms before menopause (Group I) and 33 developed symptoms after menopause (Group II). Following local estrogen therapy, based on the Global Pelvic Floor Symptoms Bother Questionnaire, improvement of OAB symptoms was reported by 20% of patients in Group I (p = 0.414) and 64% of patients in Group II, (p = 0.002). Based on the PPIUS scale, diminution in urinary urgency was experienced by 20% of patients in Group I (p = 0.68) and 66% of patients in Group II (p = 0.036). Improved VHI scores were graded statisticaly significant in both groups (Group I in 100% of women, p = 0.005 vs. 76% in Group II, p = 0.004). Conclusions: Our results indicate that local estrogen therapy is more effective in women who develop OAB after menopause.

Estrogen therapy after breast cancer diagnosis and breast cancer mortality risk.

PURPOSE: The safety of local estrogen therapy in patients on adjuvant endocrine treatment is questioned, but evidence on the issue is scarce. This nested case-control registry-based study aimed to investigate whether estrogen therapy affects breast cancer mortality risk in women on adjuvant endocrine treatment. METHODS: In a cohort of 15,198 women diagnosed with early hormone receptor (HR)-positive breast cancer and adjuvant endocrine treatment, 1262 women died due to breast cancer and were identified as cases. Each case was matched with 10 controls. Exposure to estrogen therapy with concurrent use of aromatase inhibitors (AIs), tamoxifen, or both sequentially, was compared between cases and controls. RESULTS: No statistically significant difference in breast cancer mortality risk was seen in patients with exposure to estrogen therapy concurrent to endocrine treatment, neither in short-term or in long-term estrogen therapy use. CONCLUSIONS: The study strengthens current evidence on local estrogen therapy use in breast cancer survivors, showing no increased risk for breast cancer mortality in patients on adjuvant AIs or tamoxifen.

Real-world practice of estrogen therapy after surgery for endometrial cancer: a descriptive study using a Japanese claims database.

BACKGROUND: Estrogen therapy (ET) plays a key role in maintaining the post-surgical quality of life of patients with endometrial cancer. This study investigated the reality of the use of ET after endometrial cancer surgery in Japan. METHODS: Using a healthcare database in Japan, patients who underwent surgery for endometrial cancer between the ages of 40 and 59 years from January 2006 to March 2021 were included. The cumulative prescriptions of ET after endometrial cancer surgeries in patients who had received chemotherapy or radiation therapy (adj-group) and those who did not (non-adj-group) was estimated using the Kaplan-Meier method. RESULTS: Of the 1475 patients, 115 received ET, among whom transdermal estradiol was initiated in 100 (87.0%) individuals. The cumulative proportions of ET prescription 24 months after surgery [95% confidence intervals (CIs)] were 0.088 [0.072, 0.11] in the non-adj-group and 0.058 [0.040, 0.084] in the adj-group. The cumulative proportion [95% CI] of women who received ET at 24 months after surgeries decreased with increasing age, ranging from 0.29 [0.21, 0.38] in the 40‒44 years old to 0.009 [0.002, 0.034] in the 55‒59 years old women in the non-adj-group and from 0.17 [0.094, 0.31] in the 40‒44 years old to 0 in the 55‒59 years old women in the adj-group. CONCLUSION: The present study shows that ET after endometrial cancer surgery may be underused, even in women who underwent surgery between 40 and 44 years of age and without adjuvant therapy.

Vaginal Hormone Therapy for Conditions of the Lower Urinary Tract.

PURPOSE OF REVIEW: Up to half of postmenopausal women experience genitourinary symptoms secondary to hormone deficiency, and there is little consensus on the use of vaginal hormone therapy (VHT) for lower urinary tract symptoms (LUTS) in these patients. This is a review of the scientific literature in the last decade evaluating the use of VHT for disorders of the lower urinary tract including overactive bladder (OAB), stress urinary incontinence (SUI), recurrent urinary tract infections (UTI), and interstitial cystitis/bladder pain syndrome (ICS/BPS). RECENT FINDINGS: Vaginal estrogen therapy improves OAB symptoms in postmenopausal women, but results are mixed when VHT is used in combination with other treatments. There is inconclusive or limited data for the use of VHT to treat SUI and IC/BPS. Vaginal estrogen and prasterone (DHEA) therapies have demonstrated efficacy as treatment modalities for patients who experience recurrent UTIs. VHT preparations show efficacy for the treatment of certain LUTS and can be considered in carefully selected patients when clinically indicated.

Neuregulin modulates hormone receptor levels in breast cancer through concerted action on multiple signaling pathways.

The Neuregulins (NRGs) are growth factors that bind and activate ErbB/HER receptor tyrosine kinases. Some reports have described an interplay between this ligand-receptor system and hormonal receptors in breast cancer. However, the mechanisms by which NRGs regulate hormonal receptor signaling have not been sufficiently described. Here, we show that in breast cancer cells the activation of NRG receptors down-regulated ERα through a double mechanism that included post-transcriptional and transcriptional effects. This regulation required the concerted participation of three signaling routes: the PI3K/AKT/mTOR, ERK1/2, and ERK5 pathways. Moreover, these three routes were also involved in the phosphorylation of ERα at serines 118 and 167, two residues implicated in resistance to endocrine therapies. On the other hand, NRGs conferred resistance to fulvestrant in breast cancer cells and this resistance could be reversed when the three pathways activated by NRGs were simultaneously inhibited. Our results indicate that estrogen receptor-positive (ER+) breast tumors that can have access to NRGs may be resistant to fulvestrant. This resistance could be overcome if strategies to target the three main pathways involved in the interplay between NRG receptors and ERα could be developed.

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.

Topical estrogen therapy ameliorates bladder estrogen receptor ß expression in female patients with overactive bladder.

OBJECTIVE: To explore the effect of topical estrogen therapy on the expression of estrogen receptor ß (ERß) in bladder tissue of female patients with overactive bladder (OAB). METHODS: A total of 58 female OAB patients who were treated in the Affiliated Hospital of Qinghai University were included in this retrospective study. The patients were divided into an estrogen group (28 cases) and a tolterodine group (30 cases). In the estrogen group, patients received topical vaginal estrogen treatment (0.5 mg daily) for 3 consecutive weeks and this was followed by a one-week interval. In the tolterodine group, patients received tolterodine (4 mg once daily) for 3 consecutive weeks and this was followed by a one-week interval. All patients underwent cystoscopy and completed Overactive Bladder questionnaire short form (OAB-q SF). The expression of ERß in the bladder tissue was detected by immunohistochemistry. RESULTS: After 12 weeks, there was no statistical difference in the OAB-q scores between the tolterodine and estrogen groups. However, tolterodine treatment significantly improved urinary incontinence than estrogen treatment (P = 0.03). After 12 weeks of estradiol treatment, the expression of ERß in the bladder tissue was significantly higher than that in the tolterodine group (P < 0.05). CONCLUSION: Topical estrogen therapy ameliorates OAB in female patients, and this may be related to improved ERß expression in the bladder mucosa.

The Impact of Testosterone Therapy on Cardiovascular Risk Among Postmenopausal Women.

Purpose: To summarize the current state of knowledge surrounding the impact of testosterone therapy on cardiovascular risk factors in postmenopausal women. Methodology: In this scoping review, a comprehensive search of peer-reviewed literature was conducted in adherence to a methodological framework comprising 4 distinct stages: conceptualizing a comprehensive search strategy, screening relevant publications, extracting pertinent data, and organizing and synthesizing the resultant findings. The search used electronic databases, including MEDLINE, Embase, and Google Scholar, to ensure an exhaustive survey of the available literature. Results: The database search yielded 150 articles, including systematic reviews, registered trials, and peer-reviewed studies, of which 48 duplicates were removed. Following the title/abstract screening, 36 publications were included in the full-text review. On completion of the full-text review, using the inclusion/exclusion criteria, 29 articles were excluded and 7 remained for data extraction and qualitative synthesis. Main Conclusion: Existing research provides promising insights into the benefits of low-dose testosterone therapy, typically combined with estrogen therapy. These benefits may include positive impacts on body composition, functional capacity, insulin sensitivity, inflammatory markers, and cholesterol. However, there remains a substantial lack of knowledge surrounding the effects and mechanisms behind testosterone therapy in postmenopausal women in relation to its impacts on cardiovascular risk. High-quality, evidence-based clinical intervention research is needed to investigate testosterone therapy's potential implication on cardiovascular risk factors in post-menopausal women.

Is Erbium/Neodymium Laser Combination Therapy an Effective Treatment Option for Interstitial Cystitis/Bladder Pain Syndrome With Vulvodynia?

Interstitial cystitis/bladder pain syndrome (IC/BPS) is often associated with vulvodynia and poor vaginal health. IC/BPS causes pelvic and bladder pain and urinary symptoms, which considerably reduce the quality of life. To date, this condition has no definitive cure. Local estrogen therapy (LET) has been proposed as a treatment for vulvodynia and poor vaginal health to improve the symptoms of IC/BPS. However, chronic LET could be contraindicated or not desired in some patients. The present study reports the case of a 55-year-old postmenopausal woman with IC/BPS who was successfully treated with combined vaginal erbium (VEL)/neodymium (Nd:YAG) laser (VEL+Nd:YAG) therapy. The patient presented with a five-year history of pelvic pain and urinary frequency. Direct approaches for the bladder (such as hydrodistension, anticholinergic drugs, and transurethral Hunner lesion ablation/cauterization) were conducted with inconsistent results. Immediately prior to the patient's presentation, LET was administered for 12 weeks; however, this therapy resulted in mild improvement and poor patient satisfaction. After presentation, VEL+Nd:YAG therapy was conducted once a month for three months. The patient reported considerable decrease in pain during urination. The improved symptoms were maintained for six months after the last therapy session. These results suggest that VEL+Nd:YAG therapy is an effective method for improving symptoms in patients with IC/BPS.

A Green Blue LED-Driven Two-Liquid-Phase One-Pot Procedure for the Synthesis of Estrogen-Related Quinol Prodrugs.

Quinol derivatives of estrogens are effective pro-drugs in steroid replacement therapy. Here, we report that these compounds can be synthesized in one-pot conditions and high yield by blue LED-driven photo-oxygenation of parent estrogens. The oxidation was performed in buffer and eco-certified 2-methyltetrahydrofuran as the two-liquid-phase reaction solvent, and in the presence of meso-tetraphenyl porphyrin as the photosensitizer. Two steroidal prodrugs 10ß, 17ß-dihydroxyestra-1,4-dien-3-one (DHED) and 10ß-Hydroxyestra-1,4-diene-3,17-dione (HEDD) were obtained with high yield and selectivity.

Testosterone suppression combined with high dose estrogen as potential treatment of SARS-CoV-2. A mini review.

Compared to females, males experience severe acute respiratory syndrome due to COVID-19 (SARS-CoV-2) more often, and also die more frequently from COVID-19. Testosterone has inhibitory and estrogens have favorable effects on the immune system. Both ACE2 and TMPRSS2 are specific host-cellular proteins stimulating viral entry in cells and SARS-CoV-2. Both proteins can be suppressed by inhibition of testosterone levels and by stimulation of estrogen levels. Therefore, both androgen-deprivation therapy (ADT) and estrogen therapy (ET) may decrease COVID-19 virus cell entry. Literature was searched for evidence of COVID-19 treatment benefits with estrogens, progesterone, androgen deprivation, and anti-androgens. Data supporting the effect of ADT on SARS-CoV-2 are sparse and inconsistent. The benefit of anti-androgen therapy is inconsistent. Data on the effect of ET were not found. Indirect estrogen data related to menopausal hormone therapy and hormonal contraception are favorable. In a small study, progesterone had some beneficial effects. The combination of ADT and ET (ADET) has never been studied as a treatment option for SARS-CoV-2. Based on the mode of action of the combination, it is hypothesized that ADET may be an effective and safe treatment of SARS-CoV-2, to be confirmed in a clinical trial.