Search Results (40)

Endometriosis is a chronic estrogen-dependent condition affecting women of reproductive age and commonly presents with dysmenorrhea, chronic pelvic pain, dyspareunia, and infertility. In a substantial proportion of patients, pain persists despite first-line hormonal treatment, making alternative pharmacologic strategies necessary. GnRH agonists and antagonists act primarily by suppressing ovarian estrogen production and thereby reduce an important hormonal driver of disease activity. Although both classes are effective for pain relief, they differ in onset of action, reversibility, tolerability, and suitability for prolonged use. This narrative review summarizes the current evidence on GnRH-based therapies for endometriosis-associated pain, with particular attention to biological rationale, clinical efficacy, safety, and the role of add-back therapy. Overall, both agonists and antagonists appear to provide clinically significant symptom improvement, especially in women who do not respond adequately to oral contraceptives or progestins. Their clinical use, however, is limited by hypoestrogenic adverse effects such as vasomotor symptoms and bone mineral density loss, which often require monitoring and adjunctive add-back therapy. Oral GnRH antagonists may offer practical advantages in selected patients through rapid action, the absence of a flare effect, and dose-adjustable hormonal suppression, although treatment choice must also consider long-term safety, cost, access, and individual patient characteristics. In summary, GnRH analogues remain useful second-line options, but treatment should be individualized according to symptom severity, previous treatment response, reproductive goals, tolerability, bone health, cost, and availability. Full article

Reproductive efficiency is a critical determinant of productivity and profitability in both dairy and beef cattle systems. Progesterone-based estrus synchronization protocols have emerged as essential tools to control the timing of ovulation, enhance artificial insemination efficiency, and optimize herd reproductive performance. These protocols exploit the physiological regulation of the hypothalamic–pituitary–ovarian axis, maintaining elevated progesterone levels to suppress ovulation and coordinating luteolysis and follicular wave emergence through prostaglandins, GnRH analogues, and, in some cases, equine chorionic gonadotropin. In beef cattle, progesterone supplementation facilitates fixed-time artificial insemination, shortens calving intervals, and improves calf crop uniformity, whereas in dairy cows it mitigates poor estrus detection, enhances service rates, and reduces days open. Fertility outcomes are influenced by cow physiological status, metabolic condition, and protocol adherence, with pregnancy per AI typically ranging from moderate to high in beef cattle and lower in lactating dairy cows. Economic evaluation indicates that these protocols are cost-effective in herds with moderate to large size, low estrus detection efficiency, and intensive management, although labor, drug costs, and handling requirements must be considered. Critical analysis suggests that synchronization cannot compensate for underlying nutritional, health, or metabolic deficiencies, and future research should focus on precision application, individualized protocols, and integration with automated reproductive monitoring to improve both biological and economic efficiency. This review summarizes physiological principles, protocol designs, practical applications, fertility outcomes, and economic considerations of progesterone-based estrus synchronization in cows, highlighting current challenges and perspectives for enhanced reproductive management. Full article

Background: Uterine fibroids (leiomyomas) are the most common benign tumors in women of reproductive age and represent a significant cause of abnormal uterine bleeding, pelvic pain, infertility, and reduced quality of life. Contemporary management has evolved toward individualized, uterus-sparing approaches, incorporating pharmacological and minimally invasive strategies alongside traditional surgical methods. Methods: This narrative review was conducted based on a comprehensive search of PubMed/MEDLINE, Scopus, and Web of Science databases for studies published between January 2010 and December 2025. The search strategy combined Medical Subject Headings (MeSH) and free-text terms related to uterine fibroids and their management. Eligible studies included clinical trials, systematic reviews, and meta-analyses focusing on pharmacological, minimally invasive, and surgical treatments in adult women. The review was prepared in accordance with the Scale for the Assessment of Narrative Review Articles (SANRA) recommendations to improve methodological transparency and quality of reporting. Results: A total of 97 studies were included in the qualitative synthesis. Minimally invasive techniques, including uterine artery embolization (UAE), radiofrequency ablation (RFA), and high-intensity focused ultrasound (HIFU), demonstrate high efficacy in symptom control and improvement of quality of life, with shorter recovery times and lower complication rates compared to conventional surgery. However, their impact on fertility remains variable and requires careful patient selection. Pharmacological therapies, particularly GnRH analogues and antagonists, effectively reduce bleeding and fibroid volume, although their long-term use is limited by side effects. Conclusions: The management of uterine fibroids should be individualized, taking into account symptom severity, fibroid characteristics, patient age, and reproductive plans. Minimally invasive and pharmacological treatments represent effective alternatives to surgery in appropriately selected patients, while surgical approaches remain essential in advanced or refractory cases. Future research should focus on optimizing personalized treatment strategies and evaluating long-term outcomes, particularly regarding fertility and recurrence. Full article

Endometriosis is associated with nociceptive pain, as well as peripheral and central sensitization. Evidence-based treatment suggestions for controlling endometriosis should be based on the convergence of the best scientific evidence, physicians’ clinical expertise, and the values and priorities of individual patients. In this non-systematic, comprehensive narrative review, data from available randomized controlled trials and meta-analyses on hormonal treatment for symptomatic endometriosis are interpreted through the lens of clinical experience. The role of patients in defining therapeutic trade-off balances is also taken into consideration. Most symptomatic patients benefit from hormonal therapy, including first-line (progestogens and estrogen-progestogen combinations) and second-line (GnRH agonists and antagonists) medications, to relieve nociceptive pain. To reduce the risk of venous and arterial thrombosis and avoid stimulating lesions, it is preferable to use combinations containing body-identical estrogens rather than ethinyl-estradiol. The main adverse effect of first-line medications is irregular bleeding, which adversely impacts efficacy, tolerability, and adherence. If progestogens and estrogen-progestogens do not improve health-related quality of life (HRQoL), promptly stepping up to GnRH analogues combined with add-back therapy is indicated. Add-on rather than upfront combination therapy is suggested. Separating the analogues and add-back therapy allows for choosing the compounds that best suit the characteristics of individual patients. Transdermal body-identical estradiol use is proposed in combination with both progestogens and GnRH analogues. Similar satisfactory outcomes are achieved with GnRH agonists and antagonists. Evidence on the use of neuromodulatory drugs to treat neuropathic and nociplastic pain is derived from studies of other chronic pain conditions and shows limited effectiveness. The two mainstays of hormonal therapy are (i) ovariostasis and (ii) amenorrhea. “Medical treatment failure” should not be declared unless a shift from first-line to second-line medications has been undertaken whenever these conditions are not met. For severely symptomatic adolescents and young women, secondary prevention through ovariostasis and amenorrhea should be pursued promptly to improve HRQoL, halt lesion progression, and preserve reproductive potential. Full article

Background: Atypical endometrial hyperplasia is a precursor of endometrial carcinoma, increasingly diagnosed in reproductive-aged women. Standard hysterectomy may constitute overtreatment. Fertility-sparing approaches, oral or local progestins, hysteroscopic resection, and combined regimens are widely used, though evidence largely derives from early-stage carcinoma. Methods: CENTRAL, EMBASE, Scopus, Web of Science, and PubMed were searched from inception to 13 April 2025. Eligible studies included premenopausal women with AEH treated with oral progestins, levonorgestrel intrauterine devices (LNG-IUDs), hysteroscopic resection, or combination regimens (e.g., oral progestins + metformin, LNG-IUD + GnRH analogues). Random-effects meta-analyses with multilevel modeling were applied. Risk of bias was assessed using RoB-2 and ROBINS-I; certainty of evidence was graded with GRADE-PRO. Results: Forty-nine studies (2313 women) were included. The pooled complete response (CR) rate was 85% (95% CI 80–89%). LNG-IUDs resulted in 88% CR and oral progestins in 80%. Combination therapies achieved up to 95% CR, though data were limited. Hysteroscopic resection combined with hormonal therapy reported high CR rates (96–97%) but relied on small, heterogeneous cohorts with uncertain reproducibility. The pooled recurrence rate was 19% (95% CI, 13–25%), lower with LNG-IUDs (14%) compared with oral progestins (22%). No response occurred in 14% overall and was lower with LNG-IUDs (13%) than oral progestins (19%). Among women attempting conception, the pooled pregnancy rate was 41%, and the live birth rate was 30%. The mean time to achieve CR was 5.6 months, whereas the mean time to recurrence was approximately 33 months. Conclusions: LNG-IUDs provide the most effective and well-supported fertility-sparing treatment for AEH, ensuring high remission with low recurrence. Despite favorable numerical outcomes, the evidence for hysteroscopic resection is limited and inconsistent, not supporting its routine use. Combination regimens may improve response but require confirmation in larger studies. Full article

Background: The management of endometriosis-associated pain has traditionally focused on analgesic efficacy. However, with high-level evidence demonstrating therapeutic equivalence among principal hormonal classes, the paradigm has shifted towards a patient-centred approach prioritising long-term tolerability and shared decision-making. Objectives: This review critically synthesises the evidence for the three main hormonal therapies—gonadotropin-releasing hormone (GnRH) analogues, dienogest, and gestrinone—focusing on their distinct tolerability and safety profiles to inform this modern clinical framework. Methods: This narrative review followed the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. The literature search was performed in PubMed, Embase, and Web of Science in June 2025. Results: Our comparative analysis, based on a structured literature search adhering to SANRA guidelines, shows that while all three classes are effective, they present distinct benefit–risk profiles: GnRH analogues offer potent pain relief but induce a hypoestrogenic state requiring add-back therapy to mitigate bone loss and vasomotor symptoms; dienogest preserves bone mineral density but is associated with challenging bleeding patterns and potential mood disturbances; gestrinone provides robust efficacy with a favourable cardiovascular and skeletal safety profile, although its androgenic effects can significantly impact patient adherence. Conclusions: In the absence of a clear hierarchy of efficacy, the optimal therapeutic choice is not determined by potency, but by a collaborative process in which patient values and tolerance for specific adverse effects guide selection. This review provides a framework to facilitate this shared decision-making (SDM) in clinical practice. Full article

Background/Objectives: This study aimed to enhance the vaginal permeation of buserelin acetate (BA), a synthetic gonadotropin-releasing hormone (GnRH) analogue, by evaluating various permeation enhancers (PEs) using a validated reversed-phase high-performance liquid chromatography (RP-HPLC) method and an ex vivo porcine vaginal model. Methods: A robust RP-HPLC method was developed and validated according to ICH Q2 (R2) guidelines to enable accurate quantification of BA in permeation samples. The analytical method demonstrated high specificity, linearity (R² = 0.9999), accuracy (98–102%), precision (%RSD < 2%), robustness, and stability. Using this method, ex vivo permeation studies were conducted with six different PEs: 2-hydroxypropyl-β-cyclodextrin, sodium dodecyl sulfate, poloxamer 188, Span 80, Tween 80, and chitosan. Results: Among all tested PEs, chitosan demonstrated the best enhancement of BA permeation. It achieved the highest flux (J) (0.64 ± 0.03 × 10⁻² µg/cm²·h) and apparent permeability coefficient (P_app) (16.20 ± 0.84 × 10⁻⁵ cm/h), both of which were statistically significantly higher (p < 0.05) than those of all other enhancer groups. Kinetic modelling indicated a non-Fickian, biphasic permeation mechanism best described by the Makoid–Banakar model. Conclusions: These findings highlight chitosan’s potential as an effective intravaginal delivery vehicle for peptide therapeutics and establish the validated HPLC method as a reliable platform for future formulation development and translational studies in mucosal drug delivery. Full article

This study evaluated the effectiveness of a 3D-printed cannula in inducing ovulation in female rabbits without exogenous GnRH analogues. A total of 325 inseminations were performed across different physiological stages: nulliparous, multiparous lactating, and multiparous non-lactating does. Two insemination methods were compared: a physical stimulation technique using the 3D-printed cannula and a control method involving hormonal induction with buserelin acetate. Females were either synchronized with eCG or left untreated. Delivery rates and litter sizes were recorded to assess fertility outcomes. Results indicated that the insemination procedure had a noticeable effect on delivery rate, with the control group showing greater rates (79%) compared to the cannula group (65%). In conclusion, these findings suggest that physical stimulation via the cannula can induce ovulation without exogenous hormones. This hormone-free approach offers a promising and welfare-friendly alternative for rabbit artificial insemination, aligning with efforts to reduce hormone use in livestock production. Further optimization of cannula design and technique may improve results, particularly in less responsive groups, supporting sustainable and ethical reproductive management. Full article

Orthotopic transplantation of ovarian tissue at one day of age is a promising solution for preserving female genetic material in avian species; using sterile recipients can ensure that all offspring are donor-derived. This study focuses on the suitability of the Mulard duck as a sterile recipient for Pekin duck donors and provides an investigation of the hormonal background. Firstly, native Pekin ovarian tissue was grafted into Mulard duck recipients, resulting in a 40% adhesion rate and follicular development in 50% of the adhered grafts. Secondly, the transplantation of cryopreserved ovarian tissue resulted in a 66% adhesion rate, with 33% of the adhered grafts showing follicular development. Ovulation occurred in 16% of the recipients with adhered grafts, but the eggs did not move into the oviduct. Estrogen levels were elevated in the recipients with adherence but were lower than in the control Pekin group, while progesterone levels remained unchanged. Consequently, recipients received buserelin acetate, a GnRH analogue, to stimulate follicular and oviductal activity. In this group, graft adhesion occurred in 31% of animals, and primordial follicle development in 25%. The hormonal levels of the recipients with adhered ovaries were elevated, but the GnRH analogue treatment did not affect the ovulation process. We conclude that while the Mulard duck shows potential as a sterile recipient in ovarian transplantation, several questions remain unanswered regarding the adequacy of follicular maturation and ovulation. Full article

Background/Objectives: To evaluate the effect of triptorelin on final height of girls with precocious or early puberty, compared to the untreated group, and to investigate factors that contribute to its maximum effectiveness in terms of final height. Methods: We collected for the last two decades the data of patients evaluated in our Pediatric Endocrinology Clinic for precocious (PP) (thelarche before 8 years of age) or early puberty (EP) (thelarche before 9 years of age) during the last two decades. Our final set included 178 girls (85 with precocious and 93 with early puberty, of whom 85 received triptorelin). Final heights, measured and documented by health professionals, and the exact date of menarche were collected after telephone communication. Logistic regression analysis assessed the effect of various parameters on the response to treatment. Results: Τhe difference in mean standard deviation (ΔSDS) of final and midparental height did not show significant difference between treated and untreated girls (ΔHeight SDS (Final − Midparental): −0.20 ± 0.89 vs. −0.28 ± 0.83, p = 0.243). The results were similar when we compared the EP (−0.22 ± 0.71 vs. −0.17 ± 0.83, p = 0.778) and PP (−0.19 ± 1.04 vs. −0.39 ± 0.83, p = 0.315) subgroups. Menarche occurred earlier in the PP group compared to the EP group (10.68 ± 1.22 vs. 11.12 ± 0.90 years, p = 0.005) and in the untreated compared to the treated group (10.31 ± 0.91 vs. 11.57 ± 0.06 years, p < 0.001 for EP, 11.53 ± 0.90 vs. 9.86 ± 0.86 years, p < 0.001 for PP). Predictors of final height were height at diagnosis (positively correlated), midparental height, and bone age at diagnosis (negatively correlated). Conclusions: There was no significant difference in final height between treated and untreated girls. Triptorelin was effective in delaying the onset of menarche. Factors contributing to a better final height in treated girls were higher height at baseline, lower midparental height, and younger bone age. Full article

Introductions: Precocious puberty initiated at a very young age causes a severe loss in height potential and should be treated with gonadotropin-releasing hormone agonists (GnRHa). Controversial findings exist regarding the efficacy of GnRHa treatment in girls with central precocious puberty (CPP) onset around the age of 8. This research assessed the impact of GnRHa treatment on the final height (FAH) of 117 girls diagnosed with CPP within this age group. Methods: This retrospective study included 117 CPP girls diagnosed at around age 8 (7–9 years old). Girls who started treatment between the ages of 8 and 9 (n = 71) and 7 and 8 (n = 46) were divided into groups 1 and 2, respectively. Predicted height (PAH), target height (TH), and FAH were calculated from medical records. Girls’ PAH, TH, and FAH were also compared between groups. Results: At beginning of treatment, the girls’ average ages were 8.59 ± 0.27 in group 1 and 7.50 ± 0.47 in group 2. In groups 1 and 2, GnRHa therapy durations were 1.97 ± 0.54 and 2.91 ± 0.61, respectively. There were no significant differences in TH (160.53 ± 5.49 vs. 160.57 ± 4.94), PAH (158.72 ± 5.23 vs. 158.35 ± 5.57), and FAH (162.42 ± 5.32 vs. 162.14 ± 5.70) between groups. FAH improved 4 cm from PAH in both (p = 0.001). Multivariate linear regression analysis showed that baseline height SDS was the main FAH predictor (Beta: 0.572, p = 0.001). Conclusions: GnRHa may improve FAH even if the treatment is delayed after age 8. However, as this improvement is limited for this age group, the therapy option should be individualized and should not be considered for all children. Full article

Objectives: This study aimed to evaluate the effectiveness of gonadotropin-releasing hormone-loaded chitosan–TPP nanoparticles (GnRH-CNPs) and prostaglandin F_2α-loaded chitosan–TPP nanoparticles (PGF_2α-CNPs) within the Ovsynch protocol for enhancing reproductive performance in heat-stressed dairy cows. Methods: Thirty-six cyclic purebred Friesian cows not detected in standing heat for more than 90 days postpartum were randomly allocated to three treatment groups. The control group (OVS, n = 12) followed the standard Ovsynch protocol with conventional doses. The ½ OVS group (n = 12) received 5 µg GnRH-CNPs on days 0 and 9, along with 250 µg PGF_2α-CNPs on day 7. While the ¼ OVS group (n = 12) was administered 2.5 µg GnRH-CNPs on days 0 and 9, with 125 µg PGF_2α-CNPs on day 7. Ovarian follicular dynamics and corpus luteum (CL) development were monitored on days 0, 4, 7, and 9 of the protocol. Serum progesterone (P₄) concentrations were measured throughout the synchronization period and on days 15 and 30 post-AI. Pregnancy was diagnosed on day 30 post-AI. Results: The ¼ OVS protocol achieved a significantly greater follicular response (p < 0.05) than other protocols. On day 4, following the first GnRH administration, the OVS group exhibited a higher number of subordinate follicles (p < 0.05) and a greater diameter of the dominant follicles (DFs), whereas the ¼ OVS group showed a greater subordinate follicle diameter (p < 0.05) and a higher number of DFs. On day 9, after PGF_2α administration, the ¼ OVS group maintained an elevated number of subordinate follicles, while larger subordinate follicle diameters were observed in the ½ OVS and OVS groups. No significant differences in DF numbers and diameters were observed among groups. P₄ concentrations remained similar across groups during treatments. Compared to control, a significantly higher value of P₄ concentration (p < 0.05) was recorded on day 15 post-AI in the ½ OVS group and on day 30 post-AI in the ¼ OVS group. These findings correlated with a higher pregnancy rate in the ¼ OVS group (65%) compared to the ½ OVS and OVS groups (40% in each). Conclusions: Nanofabrication reduced GnRH and PGF_2α dosage by 50% and 75% without impairing ovarian response and pregnancy rates. The ¼ OVS protocol notably enhanced the ovarian activity and fertility, highlighting the use of GnRH-CNPs and PGF_2α-CNPs as promising and practical approaches to enhance the fertility in dairy cattle under heat stress (HS). Full article

Endometrial cancer is the most common gynecological neoplasm with an increased incidence in the premenopausal population in recent decades. This raises the problem of managing endometrial cancer in fertile women who have not yet achieved pregnancy. In these women, after careful selection, hysterectomy may be postponed in favor of conservative management if specific requirements are met. The latest evidence is focused on early endometrial carcinoma, endometrioid histotype, Grading 1, with no evidence of myometrial infiltration. Few clinical trials have opened this possibility also for women with an endometrial cancer Grading 2 diagnosis. There are still questions about the best medical therapy, dosage, route, and duration of treatment. Oral progestins or levonorgestrel-releasing intrauterine devices appear to be the options associated with the best outcome in terms of complete response and lower recurrence rates. Other options include the use of GnRH analogues, surgical hysteroscopy, or metformin, in a therapeutic approach that takes into account the characteristics of the patient. The pursuit of pregnancy should start as soon as two consecutive endometrial biopsies are obtained 3 months apart from each other; it is recommended to refer the patients to ART centers to maximize the success rate. After having reached the fulfillment of the reproductive desire, surgical radical treatment is still recommended. Full article

Background/Objectives: Endometriosis is characterized by the presence of ectopic endometrial-like glands and stroma outside the endometrial cavity, which mainly occurs in the pelvic cavity. Pulmonary endometriosis, or thoracic endometriosis syndrome (TES), describes the rare presence of endometrial-like cells in the thoracic cavity and includes catamenial pneumothorax, catamenial hemothorax, hemoptysis, and lung nodules. Our aim is to summarize the results of all reported cases of TES. Methods: Extensive research was conducted through MEDLINE/PUBMED using the keywords “thoracic endometriosis”, “thoracic endometriosis syndrome”, “catamenial pneumothorax”, “catamenial hemoptysis”, and “TES”. Following PRISMA guidelines, all published cases of TES between January 1950 and March 2024 were included. A systematic review of 202 studies in English, including 592 patients, was performed. Results: The median age of women with TES is 33.8 years old. The most common clinical presentation is catamenial pneumothorax (68.4%), while lesions are mainly found in the right lung unilaterally (79.9%). Chest computed tomography (CT) was used alone or after an X-ray to determine the pathological findings. Ground-glass opacity nodules and cystic lesions represent the most common finding in CT, while pneumothorax is the most common finding in X-rays. Video-assisted thoracoscopic surgery (VATS) is the main therapeutic approach, usually in combination with hormonal therapy, including GnRH analogues, progestins, androgens, or combined oral contraceptives. Hormonal therapy was also administered as monotherapy. Symptom recurrence was reported in 10.1% of all cases after the treatment. Conclusions: High clinical awareness and a multidisciplinary approach are necessary for the best clinical outcome for TES patients. More studies are required to extract safer conclusions. Full article

Purpose: The purpose of this study is to evaluate the use of fertility-preserving (FP) treatments and fertility counseling that was offered in a cohort of newly diagnosed children with classical Hodgkin lymphoma (cHL). Methods: In this observational study, boys and girls with cHL aged ≤ 18 years with scheduled treatment according to the EuroNet-PHL-C2 protocol were recruited from 18 sites (5 countries), between January 2017 and September 2021. In 2023, a subset of Dutch participants (aged ≥ 12 years at time of diagnosis) and parents/guardians were surveyed regarding fertility counseling. Results: A total of 101 boys and 104 girls were included. Most post-pubertal boys opted for semen cryopreservation pre-treatment (85% of expected). Invasive FP treatments were occasionally chosen for patients at a relatively low risk of fertility based on scheduled alkylating agent exposure (4/5 testicular biopsy, 4/4 oocyte, and 11/11 ovarian tissue cryopreservation). A total of 17 post-menarchal girls (20%) received GnRH-analogue co-treatment. Furthermore, 33/84 parents and 26/63 patients responded to the questionnaire. Most reported receiving fertility counseling (97%/89%). Statements regarding the timing and content of counseling were generally positive. Parents and patients considered fertility counseling important (94%/87% (strongly agreed) and most expressed concerns about (their child’s) fertility (at diagnosis 69%/46%, at present: 59%/42%). Conclusion: Systematic fertility counseling is crucial for all pediatric cHL patients and their families. FP treatment should be considered depending on the anticipated risk and patient factors. We encourage the development of a decision aid for FP in pediatric oncology. Full article