Endometriosis-related infertility is one of the most debated topics in reproductive medicine. In recent years, prolonged pre-cycle hormonal regimens gained attention as a mean of improving the assisted reproduction technologies (ART) success rates in endometriosis patients. GnRH agonists, dienogest, medroxyprogesterone acetate, and aromatase inhibitors are the most studied medications. Conflicting results and a high risk of bias exist in almost all of the conducted studies in the field. However, current evidence suggests that pre-cycle treatment with GnRH agonists may be beneficial for patients with stage III/IV endometriosis. Dienogest and medroxyprogesterone acetate-based progestin-primed ovarian stimulation protocol was shown to be comparable to the prolonged GnRH agonists protocol. Finally, aromatase inhibitors seem to be of limited benefit to the assisted reproductive outcomes of endometriosis patients. Although it is challenging to draw any clinical conclusions, pre-cycle hormonal treatments seem to be best indicated in endometriosis patients who had previously failed ART treatment.

Uterine fibroids (UFs) are the most common female benign pelvic tumors, affecting >60% of patients aged 30-44 years. Uterine fibroids are asymptomatic in a large percentage of cases and may be identified incidentally using a transvaginal ultrasound or a magnetic resonance imaging scan. However, in approximately 30% of cases, UFs affect the quality of life and women\'s health, with abnormal uterine bleeding and heavy menstrual bleeding being the most common complaints, along with iron deficiency (ID) and ID anemia. Medical treatments used for UFs-related abnormal uterine bleeding include symptomatic agents, such as nonsteroidal antiinflammatory drugs and tranexamic acid, and hormonal therapies, including combined oral contraceptives, gonadotropin-releasing hormone agonists or antagonists, levonorgestrel intrauterine systems, selective progesterone receptor modulators, and aromatase inhibitors. Nevertheless, few drugs are approved specifically for UF treatment, and most of them manage the symptoms. Surgical options include fertility-sparing treatments, such as myomectomy, or nonconservative options, such as hysterectomy, especially in perimenopausal women who are not responding to any treatment. Radiologic interventions are also available: uterine artery embolization, high-intensity focused ultrasound or magnetic resonance-guided focused ultrasound, and radiofrequency ablation. Furthermore, the management of ID and ID anemia, as a consequence of acute and chronic bleeding, should be taken into account with the use of iron replacement therapy both during medical treatment and before and after a surgical procedure. In the case of symptomatic UFs, the location, size, multiple UFs, or coexistent adenomyosis should guide the choice with a shared decision-making process, considering long- and short-term treatment goals expected by the patient, including pregnancy desire or wish to preserve the uterus independently of reproductive goals.

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BACKGROUND: Children with congenital adrenal hyperplasia (CAH) are at risk for early puberty. Gonadotropin-releasing hormone analog (GnRHa) is frequently used and can decrease bone mineral density (BMD).
OBJECTIVE: Our aim was to investigate the effect of GnRHa therapy on BMD in a longitudinal study of patients with CAH spanning both childhood and adulthood.
METHODS: Sixty-one patients with classic CAH due to 21-hydroxylase deficiency (20 treated with GnRHa) were followed with dual-energy X-ray absorptiometry (DXA) scans at puberty onset, attainment of adult height, and during early adulthood.
METHODS: Whole body, lumbar spine, femoral neck, total hip, and distal radius BMD z-score at adult height. Longitudinal BMD and adult height were also assessed.
RESULTS: Twenty patients received GnRHa for an average of 4.5 ± 2 years. There were no differences in BMD between GnRHa-treated and -untreated groups at adult height for all sites. Overall, the follow-up DXA during early adulthood showed decreases in BMD z-scores for whole body (P = .01), lumbar spine (P < .0001), femoral neck (P = .06), total hip (P = .009), and distal radius (P = .05). GnRHa treatment correlated with improved height outcomes compared to predicted height at puberty onset after adjusting for midparental height (P = .02). Patients in both groups achieved similar adult height.
CONCLUSIONS: In children with CAH, GnRHa does not compromise BMD. However, BMD decreases with time and during the second and third decades of life is a possible effect of chronic supraphysiologic glucocorticoids. Children with CAH who experience early puberty benefit from GnRHa treatment as evidenced by the positive effect on height.

Over several decades, exogenous GnRH and agonists have been employed for controlling reproductive cascades in animals, and treating some reproductive morbidities. The administration of GnRH is used in animals to counter ovarian dysfunction, induce ovulation, and to increase conception and pregnancy rates. GnRH and its agonists are used in the treatment of cystic ovarian degeneration and repeat breeder syndrome. The development of protocols for GnRH administration by intramuscular injection, intramuscular or subcutaneous implants, and intravaginal deposition has empowered their clinical use worldwide. Currently, exogenous GnRH products are a central part of several pre- and post-breeding programs for the enhancement of fertility, including the control of estrous cycles and timing of ovulation, development of fixed-time artificial insemination protocols, improved embryo survival, and the treatment of reproductive morbidity. The aim of the present review is to summarize the application of exogenous GnRH agonists in food animal production.

The aspects of fertility preservation in women prior to surgical, gonadotoxic or radiation therapy represent a challenging topic in many disciplines and often in an interdisciplinary setting. Within an often short period of time, individual counselling and consideration must be given as to whether fertility-protective measures are useful. The implementation is ultimately decided by the patient. A prerequisite for helpful counselling is knowledge about the potential effects of cancer treatment on ovarian function as well as the implementation and potential individual benefits of fertility-protective measures. Networks such as FertiPROTEKT Netzwerk e. V. are helpful for orientation in terms of content and timely implementation of counselling and corresponding measures.
UNASSIGNED: Die Aspekte der Fertilitätsprotektion einer Frau vor einer operativen, gonadotoxischen oder Strahlentherapie stellen in vielen Fachgebieten und oft auch interdisziplinär ein herausforderndes Thema dar. In der Kürze der zur Verfügung stehenden Zeit muss individuell beraten und abgewogen werden, ob fertilitätsprotektive Maßnahmen sinnvoll sind, über deren Durchführung letztlich die Patientin entscheidet. Voraussetzung für eine hilfreiche Beratung sind Kenntnisse über die möglichen Auswirkungen der onkologischen Therapie auf die Ovarfunktion sowie die Durchführung und der potenzielle individuelle Nutzen von fertilitätsprotektiven Maßnahmen. Zur inhaltlichen Orientierung und zeitnahen Umsetzung von Beratungen und entsprechenden Umsetzungen sind Netzwerke wie FertiPROTEKT Netzwerk e. V. hilfreich.

There has been a growing interest in alternatives to surgery for controlling reproduction in tom cats, and the resultant medical options add to a practitioner\'s toolbox when handling these cases in clinical practice. It is important, however, that when suggesting these drugs, veterinarians have a good understanding of their mode of action, and their correct use and dosage.
Breeders increasingly wish to be able to switch on/off the reproductive ability of their tom cats in a controlled manner. In addition, in small animal medicine, there has been concern from some academics, and a growing number of pet cat owners, about potential long-term effects of surgical sterilisation. Further, for some cats surgical castration may not be possible due to health conditions that mean anaesthesia is unsafe. In all of these scenarios, medical alternatives to surgery can prove useful.
No special equipment or technical skills are required. A good knowledge of the medical alternatives to surgical sterilisation for controlling reproduction in a tom, and making sure the patient is a suitable candidate, are, however, important for ensuring the cat\'s health during and after treatment and the owner\'s satisfaction.
This review is aimed principally (but not exclusively) at veterinary practitioners working with cat breeders who seek a temporary arrest in their tom cat\'s reproduction. It may also help practitioners with clients who would like an alternative to surgery or with cats where anaesthesia for surgical castration is not possible.
Advances in reproductive feline medicine have resulted in improved knowledge of medical contraception. This review draws on scientific evidence-based papers that report on the mode of action, length of efficacy and potential side effects of different methods of medical contraception, as well as the authors\' own clinical experience.

Gonadotropin-Releasing Hormone (GnRH) is a decapeptide responsible for the control of the reproductive functions. It shows C- and N-terminal aminoacid modifications and two other distinct isoforms have been so far identified. The biological effects of GnRH are mediated by binding to high-affinity G-protein couple receptors (GnRHR), showing characteristic very short C tail. In mammals, including humans, GnRH-producing neurons originate in the embryonic nasal compartment and during early embryogenesis they undergo rapid migration towards the hypothalamus; the increasing knowledge of such mechanisms improved diagnostic and therapeutic approaches to infertility. The pharmacological use of GnRH, or its synthetic peptide and non-peptide agonists or antagonists, provides a valid tool for reproductive disorders and assisted reproduction technology (ART). The presence of GnRHR in several organs and tissues indicates additional functions of the peptide. The identification of a GnRH/GnRHR system in the human endometrium, ovary, and prostate has extended the functions of the peptide to the physiology and tumor transformation of such tissues. Likely, the activity of a GnRH/GnRHR system at the level of the hippocampus, as well as its decreased expression in mice brain aging, raised interest in its possible involvement in neurogenesis and neuronal functions. In conclusion, GnRH/GnRHR appears to be a fascinating biological system that exerts several possibly integrated pleiotropic actions in the complex control of reproductive functions, tumor growth, neurogenesis, and neuroprotection. This review aims to provide an overview of the physiology of GnRH and the pharmacological applications of its synthetic analogs in the management of reproductive and non-reproductive diseases.

OBJECTIVE: Is it possible to reduce the cost of GnRH agonist treatment for endometriosis by using non-standard dosing regimens?
CONCLUSIONS: An extended-interval dosing regimen of a 3.75 mg depot formulation of triptorelin injected every 6 weeks instead of every 4 weeks reduces the cost by one-third without compromising the effect on pain relief.
BACKGROUND: Cost constitutes a limit to prolonged GnRH agonists use. Alternative modalities to reduce the economic burden of GnRH agonist treatment have been anecdotally attempted.
UNASSIGNED: A systematic review was conducted to evaluate and compare the effect of three alternative modalities for GnRH use in women with endometriosis, i.e. intermittent oestrogen deprivation therapy, reduced drug dosage, and extended-interval dosing regimens of depot formulations. A PubMed and Embase search was initially conducted in October 2022 and updated in January 2023 using the following search strings: (endometriosis OR adenomyosis) AND (GnRH-agonists OR gonadotropin-releasing hormone agonists OR triptorelin OR leuprorelin OR goserelin OR buserelin OR nafarelin). Full-length articles published in English in peer-reviewed journals since 1 January 1980, and reporting original data on GnRH agonist treatment of pain symptoms associated with endometriosis were selected.
METHODS: Information was extracted on study design, GnRH-agonist used, dosage, total duration of therapy, side effects, treatment adherence, and pelvic pain relief. Reviews, commentaries, conference proceedings, case reports, and letters to the editor were excluded.
RESULTS: Of the 1664 records screened, 14 studies regarding clinical outcomes associated with the 3 considered alternative modalities for GnRH agonist use were eventually included (intermittent oestrogen deprivation therapy, n = 2; low-dose or \'draw-back\' therapy, n = 8; extended-interval dosing regimen, n = 4). Six studies were randomized controlled trials (RCTs) (double blind, n = 2) and eight adopted a prospective cohort design (non-comparative, n = 6; comparative, n = 2). A total of 776 women with endometriosis were recruited in the above studies (intermittent oestrogen deprivation therapy, n = 77; low-dose or \'draw-back\' therapy, n = 528; extended-interval dosing regimen, n = 171). Robust data demonstrating cost saving without detrimental clinical consequences were available for the extended-interval dosing regimen only. In particular, the 3.75 mg triptorelin depot preparation inhibits ovarian function for a longer period compared with the 3.75 mg leuprorelin depot preparation, allowing injections every 6 instead of 4 weeks. Based on the cost indicated by the Italian Medicine Agency for the 3.75 mg triptorelin depot preparation, this would translate in a yearly saving of €744.60 (€2230.15-€1485.55; -33.4%).
CONCLUSIONS: The quality of the evidence reported in the selected articles was not formally evaluated and a quantitative synthesis could not be performed. Some studies were old and the tested therapeutic approaches were apparently obsolete. Only cost containment associated with GnRH analogue use, and not cost-effectiveness, has been addressed.
CONCLUSIONS: Consuming less resources without negatively impacting on health outcomes carries ethical and practical implications for individuals and the community, as this approach may result in overall increased healthcare access.
BACKGROUND: This study was supported by the Italian Ministry of Health (Ricerca Corrente 2023, IRCCS Ca\' Granda Ospedale Maggiore Policlinico Milano). E.S. discloses payments from Ferring for research grants and honoraria from Merck-Serono for lectures. All other authors declare they have no conflict of interest.
BACKGROUND: N/A.

Androgen-deprivation therapy (ADT) is the primary systemic therapy for treating advanced or metastatic prostate cancer (PCa), which has improved survival outcomes in patients with PCa. However, ADT may develop metabolic and cardiovascular adverse events that impact the quality of life and lifespan in PCa survivors. The present study was designed to establish a murine model of ADT with a gonadotropin-releasing hormone (GnRH) agonist leuprolide and to investigate its effects on metabolism and cardiac function. We also examined the potential cardioprotective role of sildenafil (inhibitor of phosphodiesterase 5) under chronic ADT. Middle-aged male C57BL/6J mice received a 12-wk subcutaneous infusion via osmotic minipumps containing either saline or 18 mg/4 wk leuprolide with or without 1.3 mg/4 wk sildenafil cotreatment. Compared with saline controls, leuprolide treatment significantly reduced prostate weight and serum testosterone levels, confirming chemical castration in these mice. The ADT-induced chemical castration was not affected by sildenafil. Leuprolide significantly increased the weight of abdominal fat after 12-wk treatment without a change in total body weight, and sildenafil did not block the proadipogenic effect of leuprolide. No signs of left ventricular systolic and diastolic dysfunction were observed throughout the leuprolide treatment period. Interestingly, leuprolide treatment significantly elevated serum levels of cardiac troponin I (cTn-I), a biomarker of cardiac injury, and sildenafil did not abolish this effect. We conclude that long-term ADT with leuprolide increases abdominal adiposity and cardiac injury biomarker without cardiac contractile dysfunction. Sildenafil did not prevent ADT-associated adverse changes.