Safety of vaginal oestrogens for genitourinary symptoms in women with breast cancer.

BACKGROUND: Oestrogen deprivation is the mainstay of treatment for women with hormone receptor-positive breast cancer, but unfortunately it causes multiple side effects that can significantly impair quality of life. Genitourinary symptoms are very common and although these symptoms can be effectively managed with vaginal oestrogens, concerns about their safety in women with breast cancer limits their use. OBJECTIVE: The aim of this review is to provide a summary of the data on the safety of vaginal oestrogens in women with breast cancer to help general practitioners advise their patients in this situation. DISCUSSION: Although there are no large randomised prospective studies to assess safety, the current evidence suggests reassurance can be provided to the majority of women with a history of breast cancer considering vaginal oestrogens. Consultation with the oncology team is advised for women taking aromatase inhibitors, where the safety of vaginal oestrogens is less certain.

Genitourinary syndrome of lactation: a new perspective on postpartum and lactation-related genitourinary symptoms.

BACKGROUND: The genitourinary syndrome of menopause (GSM) is a well-documented condition characterized by a range of genitourinary symptoms in peri- and postmenopausal women. As with GSM, postpartum lactating women experience reduced estrogen and androgen levels. However, there is limited research on the impact of symptoms during the postpartum breastfeeding period. OBJECTIVES: The aim was to review the literature for genitourinary health in the postpartum breastfeeding population and summarize key findings and potential treatments. METHODS: We performed a comprehensive literature review in PubMed, Google Scholar, and Scopus from inception of database to November 2023 using the following keywords individually and in combination: "physiology of postpartum" or "physiology of lactogenesis" or "vulvovaginal health" or "vaginal atrophy" or "vaginal dryness" or "dyspareunia" or "urinary incontinence" or "lactation" or "breastfeeding" or "vaginal estrogen." All identified articles published in English were considered. Relevant studies were extracted, evaluated, and analyzed. The work presented in this article represents a summative review of the identified literature. RESULTS: During lactation, high levels of prolactin inhibit estrogen and androgen secretion via negative feedback, which leads to an increased prevalence of vulvovaginal atrophy, vaginal dryness, dyspareunia, and urinary incontinence in lactating postpartum women. Despite these highly prevalent and potentially devastating symptoms, there is a lack of consistent screening at postpartum visits and no treatment guidelines available to health care providers. CONCLUSION: Postpartum breastfeeding women experience similar physiology and symptoms to the postmenopausal phase, as seen in GSM. We propose the introduction of a novel term to describe the genitourinary changes seen in postpartum breastfeeding individuals: genitourinary syndrome of lactation. The diagnostic use of genitourinary syndrome of lactation will equip health care providers with an all-encompassing term to bring awareness to the symptoms experienced by postpartum breastfeeding individuals and lead to improved screening and treatment for the high numbers of individuals experiencing these genitourinary changes.

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.

A Review on Therapeutic Effects of Labisia pumila on Female Reproductive Diseases.

The Labisia pumila (LP) is a traditional plant that is locally known as Kacip Fatimah, Selusuh Fatimah, or Pokok Ringgang by the Malaysian indigenous people. It is believed to facilitate their childbirth, treating their postchild birth and menstrual irregularities. The water extract of LP has shown to contain bioactive compounds such as flavonoids, ascorbic acid, ß-carotene, anthocyanin, and phenolic acid, which contribute extensive antioxidant, anti-inflammatory, antimicrobial, and antifungal. The LP ethanolic extract exhibits significant estrogenic effects on human endomentrial adenocarcinoma cell in estrogen-free basal medium and promoting an increase in secretion of alkaline phosphate. Water based has been used for many generations, and studies had reported that it could displace in binding the antibodies and increase the estradiol production making it similar to esterone and estradiol hormone. LP extract poses a potential and beneficial aspect in medical and cosmeceutical applications. This is mainly due to its phytoestrogen properties of the LP. However, there is a specific functionality in the application of LP extract, due to specific functional group in phytoconstituent of LP. Apart from that, the extraction solvent is important in preparing the LP extract as it poses some significant and mild side effects towards consuming the LP extracts. The current situation of women reproductive disease such as postmenopausal syndrome and polycystic ovary syndrome is increasing. Thus, it is important to find ways in alternative treatment for women reproductive disease that is less costly and low side effects. In conclusion, these studies proven that LP has the potential to be an alternative way in treating female reproductive related diseases such as in postmenopausal and polysystic ovarian syndrome women.

Clinical manifestations and evaluation of postmenopausal vulvovaginal atrophy.

INTRODUCTION: It is estimated that 50% of women will suffer a severe form of vulvovaginal atrophy (VVA) related to menopause. Equally, young women may temporarily present this clinical problem while receiving various pharmacological or endocrine treatments or radiotherapy. AIM: To determine clinical and diagnostic exams required to confirm the presence of VVA (also referred to as atrophic vaginitis, urogenital atrophy, or genitourinary syndrome of menopause) and rule out other genital or pelvic clinical conditions. MATERIALS AND METHODS: Literature review searches were carried out on the main scientific article search engines (PubMed, SciELO, Cochrane) using different clinical terms, treatments or interventions and comorbidity related to VVA. RESULTS: The development and severity of VVA depend mainly on the duration of hypoestrogenism. Hypoestrogenism causes changes in the urogenital tissue, generating signs and symptoms, such as dryness, burning, soreness, itching, and irritation of the genital skin. The diagnosis can be made through anamnesis (patient history), questionnaires, physical exam, and, sometimes, complementary exams. Objective vaginal assessment is essential and can be completed with the Vaginal Health Index, the Vaginal Maturation Index, or vaginal pH in the absence of infection or semen. The exclusion of other vulvovaginal organic pathology is essential to reach an accurate diagnosis and provide adequate treatment. CONCLUSIONS: The specialist should be able to identify VVA, rule out other pathologies that make a differential diagnosis and conduct proper management.

Mulheres submetidas ao transplante de medula óssea: impacto dos quimioterápicos e da doença do enxerto contra o hospedeiro sobre o sistema reprodutor / Women undergoing bone marrow transplantation: impact of chemotherapy and graft-versus-host disease (GVHD) on the feminine reproductive system

O transplante de medula óssea (TMO) é um procedimento indicado para o tratamento de doenças hematológicas, que afetam muitas mulheres jovens. O aperfeiçoamento dos cuidados durante o TMO proporciona altos índices de cura e de sobrevida. No entanto, pode deixar sequelas em vários órgãos e sistemas, entre eles o sistema reprodutor e os órgãos genitais, impactando negativamente a qualidade de vida das receptoras do TMO. O objetivo desta publicação foi realizar uma revisão narrativa sobre o tema e propor um protocolo assistencial que torne acessível os cuidados relacionados à saúde sexual e reprodutiva a esse grupo especial de mulheres, baseado em dados clínicos de um ambulatório de assistência ginecológica às mulheres transplantadas no Hospital Amaral Carvalho, em Jaú, no interior de São Paulo.(AU)

Bone marrow transplantation (BMT) is indicated for the treatment of hematological diseases which affect many young women. The improvement of care during BMT procedures provides higher cure and survival rates. however, it can cause sequelae in various organs and systems, including the reproductive system and genitals, negatively impacting quality of life. The purpose of this publication is to present a narrative review related to this theme and to propose a healthcare protocol that allows sexual and reproductive care in this special group of patients, based on the clinical experience of a gynecological outpatient clinic at the Amaral Carvalho Hospital, in Jaú (SP) which specifically care for these women.(AU)

At-Home Transvaginal Device Following Fractional Carbon Dioxide Laser Treatment for Genitourinary Syndrome of Menopause.

BACKGROUND: Device-based therapeutic approaches have been developed to treat women’s genitourinary post-menopausal symptoms. Fractional carbon dioxide laser resurfacing (FxCO2) has been demonstrated to be safe and effective in the treatment of GSM symptoms, however the results begin to wane by 12-months post-treatment. OBJECTIVE: This study aims at assessing the application of an at-home transvaginal red and infrared light device as a maintenance treatment commencing 12 months following FxCO2 laser treatment for genitourinary syndrome of menopause (GSM). STUDY DESIGN: Subjects completing 12-month follow-up after three fractional CO2 laser vulvovaginal treatments received an at-home device and monitored for GSM symptoms with long-term follow-up to 12 months (2 years post-laser). METHODS: 10 post-menopausal subjects completing 12-months follow-up after three FxCO2 vulvovaginal treatments for GSM were treated with an at-home red and infrared LED device. Treatment consisted of intravaginal application three times per week, and subjects were followed to 1, 3, 6, and 12 months. Subjects completed the vaginal assessment scale subject satisfaction, and QUID to assess for vulvovaginal and stress urinary incontinence (SUI) symptoms. RESULTS: Vulvovaginal symptoms measured by VAS were mean 89% improved at 12-month follow-up after FxCO2 and maintained at 73% improved over baseline (2 years post-laser) following an additional 12 months of at-home transvaginal light therapy (P<0.05). VAS symptoms gradually increased over the 12 months maintenance period by a mean of 17% (P<0.05). Mean subject satisfaction was 0 at baseline, 1.86 at 1 year following FxCO2, and 1.00 after an additional 1 year of at-home light therapy. SUI symptoms as measured by QUID were mean 81% improved at 12-month follow-up after FxCO2and maintained at 38% improved over baseline (2 years post-laser) following an additional 12-months of at-home light therapy (P<0.05). SUI symptoms gradually increased by a mean of 43% over the 12-month maintenance period (P<0.05). CONCLUSIONS: At-home transvaginal red and near infrared light therapy commencing at 12 months post-FxCO2 vulvovaginal treatment in a post-menopausal population maintained statistically significant improvements in vulvovaginal and SUI symptoms over the additional12-month period (2 years post-laser); however, a gradual return of symptoms suggests that laser re-treatment or combination withhormone therapy may be necessary to maintain optimal outcomes.J Drugs Dermatol. 2020;19(11):1076-1079. doi:10.36849/JDD.2020.1012.

A new treatment of genito-urinary post-menopausal atrophy with autologous micro-fragmented fat tissue: a thirty-six months follow up case series.

OBJECTIVE: Genitourinary atrophy is a menopausal pathological change determined by the definitive drop of ovarian hormones' production that can impact heavily on the health status of women, with important direct and indirect social costs. Unfortunately, available treatments are only symptomatic, and they are not able to reverse the atrophy and other related symptoms. Regenerative medicine, with single local injection of autologous micro-fractured fat tissue, could represent a viable new solution for these patients as it not only helps to relieve symptoms, but it also counteracts the mechanisms that lead to the menopausal genitourinary atrophy. The objective of this paper is to evaluate the long-term effectiveness of micro-fractured fat vulvar injection for genito-urinary atrophy in patients, affected by severe genitourinary atrophy (at least 4 symptoms lasting for at least 4 years). PATIENTS AND METHODS: We present a case series of 35 patients followed for 36 months to evaluate the effectiveness and safety of a single subcutaneous vulvar injection of autologous micro-fragmented fat tissue (MFAT). RESULTS: We have not observed any adverse effects in any patients. All symptoms, and especially pelvic pain and dyspareunia, improved in almost half of patients within 3 months. Ninety-nine percent of patients recovered completely from all symptoms after 9-12 months, reporting no relapse of the symptoms up to the third year of follow up. CONCLUSIONS: Our case series is the first case series, evaluating the long-term (3 years) safety and effectiveness of micro-fragmented adipose tissue graft for urogenital atrophy.

Pelvic floor muscle training: mechanisms of action for the improvement of genitourinary syndrome of menopause.

Objective: This study aims to investigate the mechanism of action of pelvic floor muscle training (PFMT) for the improvement of the signs and symptoms of genitourinary syndrome of menopause (GSM) in postmenopausal women with GSM and urinary incontinence (UI).Methods: Twenty-nine women were included in the secondary analysis of a single-arm feasibility study. Using color Doppler ultrasound, the peak systolic velocity, time-averaged maximum velocity, and pulsatility index of the internal pudendal and dorsal clitoral arteries were measured at rest and after a pelvic floor muscle (PFM) contraction task. PFM function was assessed by dynamometry, and vulvovaginal tissue elasticity was measured using the Vaginal Atrophy Index.Results: PFMT significantly improved blood flow parameters in both arteries (p < 0.05) and significantly increased the speed of PFM relaxation after a contraction (p = 0.003). After the intervention, a marginally significant decrease in PFM tone was observed, as well as an increase in PFM strength (p = 0.060 and p = 0.051, respectively). Finally, improvements in skin elasticity and introitus width were observed as measured by the Vaginal Atrophy Index (p < 0.007).Conclusion: Our findings suggest that PFMT improves blood flow in vulvovaginal tissues, PFM relaxation capacity, and vulvovaginal tissue elasticity in postmenopausal women with GSM and UI.

Increasing Age Predicts Increasing Residual Urine Volume.

OBJECTIVES: To determine reference values for postvoid residual (PVR) volume for patients referred to a tertiary urogynecology center. METHODS: After Institutional Review Board approval, we performed a retrospective chart review of all new patients presenting to our referral center. We assessed associations between PVR and patient demographics, pelvic floor symptoms, and physical examination by Wilcoxon rank sum or Kruskal-Wallis tests as appropriate. A multivariable logistic regression model was used to calculate odds ratios for patient characteristics associated with PVR in the top age range-specific decile. RESULTS: Three hundred sixty-one patients were included in the analysis. The median PVR was 20 mL (interquartile range, 1st, 3rd quartiles, 10, 50). Older age was associated with higher PVR (P < 0.001). The median PVR in participants younger than 40 years was 10 mL, ages 40 to 49 years was 18 mL, 50 to 69 years was 20 mL, 70 to 79 years was 38 mL and in women older than 79 years was 50 mL. A multivariable analysis showed that prolapse stage (odds ratio [OR], 3.46 with prolapse stage 2-4 vs stage 0-1; P = 0.001), history of stroke (OR, 7.62; [95% CI 2.17-26.77, P = 0.002]), narcotic use (OR, 2.45; [95% CI 1.01-5.92; P = 0.047]), and urinary frequency (OR, 2.61; [95% CI, 1.14-5.98; P = 0.024]) were risk factors for increased PVR (as defined at >90%ile for age), independent of the age-related elevation. CONCLUSIONS: The majority of patients presenting for urogynecologic evaluation had a low PVR with a median of 20 mL. Postvoid residual was higher for older age groups but nearly all volumes were less than 100 mL. The utility of a PVR measurement is highest for patients with pelvic organ prolapse, urinary frequency, narcotic use, or history of stroke.

Critical analysis of methods for assessing genitourinary syndrome of menopause used in clinical trials.

OBJECTIVE: The aim of the study was to determine the most used methods for assessing genitourinary syndrome of menopause by the latest studies on the subject, and to critically assess their differences and comparability. METHODS: A narrative review of the literature was conducted, employing the terms genitourinary syndrome, vaginal atrophy, urogenital atrophy, and atrophic vaginitis, to analyze methods used to assess treatment efficacy. Only controlled randomized clinical trials assessing improvement of genitourinary syndrome of menopause, conducted in the last 5 years, and considering all types of treatment, were selected. RESULTS: Of the 37 studies included, 24 combined both objective and subjective methods thereby ensuring reproducibility and efficacy of symptom relief of the treatment analyzed. The vaginal maturation index was the most used objective method, followed by vaginal pH. One study used histological and immunohistochemistry tests. Regarding subjective methods, the "Most bothering Symptom" and other questionnaires as the Female Sexual Function Index for sex life, the Verbal Rating Scale, among others, were used. CONCLUSIONS: Despite the heterogeneity observed, particularly for subjective assessment of symptoms, there was a tendency to standardize methods and to use an objective method together with a subjective, which seems to be fundamental to guarantee reproducibility and comparability of results of each treatment analyzed. Histological and immunohistochemistry tests may be an option as an objective method in further studies, to better assess thickness, vascularization, among other parameters.

Practical Treatment Considerations in the Management of Genitourinary Syndrome of Menopause.

Genitourinary syndrome of menopause is a condition comprising the atrophic symptoms and signs women may experience in the vulvovaginal and bladder-urethral areas as a result of the loss of sex steroids that occurs with menopause. It is a progressive condition that does not resolve without treatment and can adversely affect a woman's quality of life. For a variety of reasons, many symptomatic women do not seek treatment and, of those who do, many are unhappy with their options. Additionally, many healthcare providers do not actively screen their menopausal patients for the symptoms of genitourinary syndrome of menopause. In this review, we discuss the clinical presentation of genitourinary syndrome of menopause as well as the treatment guidelines recommended by the major societies engaged in women's health. This is followed by a review of available treatment options that includes both hormonal and non-hormonal therapies. We discuss both the systemic and vaginal estrogen products that have been available for decades and remain important treatment options for patients; however, a major intent of the review is to provide information on the newer, non-estrogen pharmacologic treatment options, in particular oral ospemifene and vaginal prasterone. A discussion of adjunctive therapies such as moisturizers, lubricants, physical therapy/dilators, hyaluronic acid, and laser therapy is included. We also address some of the available data on both the patient and healthcare providers perspectives on treatment, including cost, and touch briefly on the topic of treating women with a history of, or at high risk for, breast cancer.

Oxidative stress in biological systems and its relation with pathophysiological functions: the effect of physical activity on cellular redox homeostasis.

The body of evidence from the past three decades demonstrates that oxidative stress can be involved in several diseases. This study aims to summarise the current state of knowledge on the association between oxidative stress and the pathogenesis of some characteristic to the biological systems diseases and aging process. This review also presents the effect of physical activity on redox homeostasis. There is strong evidence from studies for participation of reactive oxygen and nitrogen species in pathogenesis of acute and chronic diseases based on animal models and human studies. Elevated levels of pro-oxidants and various markers of the oxidative stress and cells and tissues damage linked with pathogenesis of cancer, atherosclerosis, neurodegenerative diseases hypertension, diabetes mellitus, cardiovascular disease, atherosclerosis, reproductive system diseases, and aging were reported. Evidence confirmed that inflammation contributes widely to multiple chronic diseases and is closely linked with oxidative stress. Regular moderate physical activity regulates oxidative stress enhancing cellular antioxidant defence mechanisms, whereas acute exercise not preceded by training can alter cellular redox homeostasis towards higher level of oxidative stress. Future studies are needed to clarify the multifaceted effects of reactive oxygen/nitrogen species on cells and tissues and to continue study on the biochemical roles of antioxidants and physical activity in prevention of oxidative stress-related tissue injury.

Interpersonal trauma and aging-related genitourinary dysfunction in a national sample of older women.

BACKGROUND: Among reproductive-aged women, exposure to interpersonal trauma is associated with genitourinary symptoms. Little is known about the relationship between these exposures and the genitourinary health of older women, who tend to experience different and more prevalent genitourinary symptoms because of menopause and aging. OBJECTIVES: In this study, we examined relationships between common types of interpersonal trauma and aging-related genitourinary dysfunction among older women. STUDY DESIGN: We analyzed data from the National Social Life, Health, and Aging Project, a national area probability sample of older community-dwelling adults born between 1920 and 1947. We used cross-sectional data from home-based study visits conducted in 2005-2006 to examine interpersonal violence exposures (any lifetime sexual assault, past-year emotional and physical abuse), and past-year genitourinary symptoms (urinary incontinence, other urinary problems, and vaginal pain/lubrication problems with sexual intercourse) among women participants. Multivariable logistic regression models were used to relate interpersonal violence and genitourinary symptoms, adjusting for age, race/ethnicity, body mass index, education, marital status, parity, hormone therapy, depressive and anxiety symptoms, and self-reported health. In exploratory models, we further adjusted for vaginal maturation, a tissue-specific marker of aging-related urogenital atrophy obtained from vaginal self-swabs. RESULTS: In this national sample of 1551 older women (mean age 69 ± 2 years), 9% reported sexual assault, 23% reported emotional abuse, and <1% reported physical abuse. Urinary incontinence and other urinary problems were reported by 42% and 17%, respectively, and 42% of sexually active women (n = 527) reported vaginal symptoms with intercourse. In multivariable regression analyses adjusted for age, race/ethnicity, education, marital status, parity, hormone therapy, anxiety, depressive symptoms, and self-reported health, women with any lifetime history of sexual assault had 2.5 times the odds (95% confidence interval, 1.0-6.3) of vaginal symptoms, while women who reported past-year emotional abuse had higher odds of urinary incontinence (odds ratio, 1.7, 95% confidence interval, 1.2-2.4) and other urinary problems (odds ratio, 1.8, 95% confidence interval, 1.2-2.8). Among women who provided vaginal self-swabs (n = 869), adjustment for vaginal maturation-attenuated associations with other urinary problems (odds ratio, 1.6, 95% confidence interval, .9-2.6) and vaginal symptoms (odds ratio, 2.2, 95% confidence interval, 0.8-5.8). CONCLUSION: Sexual assault and emotional abuse may play a role in the development or experience of aging-related genitourinary dysfunction in older women. Clinicians caring for older women should recognize the prevalence and importance of traumatic exposures in health related to menopause and aging.

Estradiol vaginal inserts (Imvexxy): effective in genitourinary syndrome of menopause without increasing systemic estrogen levels.

Many women suffer from the genitourinary syndrome of the menopause (GSM), in particular pathological changes that occur in the vagina due to the reduction in their production of estrogens. TherapeuticsMD has developed Imvexxy, small softgel capsules that contain solubilized estradiol and that are inserted vaginally by women twice a week, every 3 to 4 days. These vaginal inserts have been found to readily supply estradiol to the vagina and to result in significant improvement in the GSM signs and symptoms these women had been experiencing. At the same time, pharmacokinetic studies have demonstrated that the small doses of estradiol used do not increase systemic blood levels of estrogens above baseline values, thus greatly reducing the likelihood of unwanted systemic effects of estradiol. The placebo used in clinical trials, which only contained the 'inactive' ingredients in Imvexxy, had partial efficacy, the result either of a placebo effect or of the use of MIGLYOL 812 N to keep the estradiol in solution.

Genitourinary Changes with Aging.

Both chronologic aging and menopause affect the physical, physiologic, and microbiological characteristics of the genitourinary tract. The genitourinary syndrome of menopause, characterized by vulvovaginal and lower urinary tract signs and symptoms, is prevalent and has a significant negative impact on women's lives. In this article, the authors detail the genitourinary tract changes associated with menopause and/or aging. They also review the 2014 North American Menopause Society's definition of the genitourinary syndrome of menopause and present the epidemiology and impact of genitourinary aging in midlife and older women, namely, vulvovaginal, urinary, and sexual symptoms.

The gonadotropin system, lessons from animal models and clinical cases.

This review article centers upon family of gonadotropin hormones which consists of two pituitary hormones - follicle-stimulating hormone (FSH) and luteinizing hormone (LH) as well as one non-pituitary hormone - human chorionic gonadotropin (hCG) secreted by placenta, and their receptors. Gonadotropins play an essential role in proper sexual development, puberty, gametogenesis, maintenance of pregnancy and male sexual differentiation during the fetal development. They belong to the family of glycoprotein hormones thus they constitute heterodimeric proteins built of common α subunit and hormone-specific ß-subunit. Hitherto, several mutations in genes encoding both gonadotropins and their receptors have been identified in humans. Their occurrence resulted in a number of different phenotypes including delayed puberty, primary amenorrhea, hermaphroditism, infertility and hypogonadism. In order to understand the effects of mutations on the phenotype observed in affected patients, detailed molecular studies are required to map the relationship between the structure and function of gonadotropins and their receptors. Nonetheless, in vitro assays are often insufficient to understand physiology. Therefore, several animal models have been developed to unravel the physiological roles of gonadotropins and their receptors.

Gonadotropin-releasing hormone analog therapeutics.

Dysregulation at any level of the hypothalamic-pituitary-gonadal (HPG) axis results in, or aggravates, a number of hormone-dependent diseases such as delayed or precocious puberty, infertility, prostatic and ovarian cancer, benign prostatic hyperplasia, polycystic ovarian syndrome, endometriosis, uterine fibroids, lean body mass, as well as metabolism and cognitive impairment. As gonadotropin-releasing-hormone (GnRH) is an essential regulator of the HPG axis, agonist and antagonist analogs are efficacious in the treatment of these conditions. GnRH analogs also play an important role in assisted reproductive therapies. This review highlights the current and future therapeutic potential of GnRH analogs and upstream regulators of GnRH secretion.