Search Results (150)

Background/Objectives: Breast cancer remains the most prevalent malignancy among women worldwide, with letrozole (LZ) serving as a critical aromatase inhibitor for hormone receptor–positive cases. However, long-term oral administration of LZ is often associated with systemic adverse effects and poor patient compliance. To overcome these limitations, new non-aqueous nanoemulgels (NEMGs) were developed for transdermal delivery of LZ. Methods: The NEMGs were formulated using glyceryl monooleate (GMO), Sepineo P600^®, Transcutol, propylene glycol, and penetration enhancers propylene glycol laurate (PGL), propylene glycol monocaprylate (PGMC), and Captex^®. Physicochemical characterization, solubility, stability, and in vitro permeation studies were conducted using Strat-M^® membranes, while in vivo pharmacokinetics were evaluated in rat models. Results: The optimized GMO/PGMC-based NEMG demonstrated significantly enhanced drug flux, higher permeability coefficients, and shorter lag times compared with other NEMGs and suspension emulgels. In vivo, transdermal application of the GMO/PGMC-based NEMG over an area of 2.55 cm² produced dual plasma absorption peaks, with 57% of the LZ dose absorbed relative to oral administration over 12 days. Shelf-life and accelerated stability assessments confirmed excellent physicochemical stability with negligible crystallization. Conclusions: The developed LZ NEMG formulations offer a stable, effective, and patient-friendly transdermal drug delivery platform for breast cancer therapy. This system demonstrates potential to improve patient compliance and reduce systemic toxicity compared to conventional oral administration. Full article

Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, with ovulation induction remaining the first-line treatment approach. Although letrozole has emerged as the most effective monotherapy, treatment resistance, side effects, and patient preferences have led to increasing interest in adjunctive or alternative approaches. This narrative review summarizes the current evidence for ovulation induction in patients with PCOS, including conventional pharmacologic agents, such as clomiphene citrate, letrozole, gonadotropins, and insulin-sensitizing agents, as well as complementary therapies, such as acupuncture and Chinese herbal medicine. We also examine emerging adjuvants, such as vitamin D, omega-3 fatty acids, sildenafil, and antioxidants that may enhance clinical pregnancy rates or improve endometrial receptivity. While robust evidence supports the use of letrozole as a first-line agent, complementary and integrative therapies may offer additional benefits, particularly in treatment-resistant or preference-driven contexts. Further high-quality studies are needed to clarify the role of combined therapeutic strategies in optimizing fertility outcomes for women with PCOS. Full article

Background/Objectives: Trophoblast cell surface antigen 2 (Trop2), a transmembrane glycoprotein overexpressed in a broad spectrum of epithelial malignancies but minimally expressed in normal tissues, has emerged as a clinically relevant prognostic biomarker and therapeutic target, particularly in breast cancer. This study aims to develop an enhanced way of targeting Trop2 expression in tumors and blocking it using extracellular vesicles (EVs) bioengineered to express a nanobody sequence against Trop2 (NB60 E). Methods: Here, a plasmid construct was designed to express the Trop2 sequence, NB60, flanked with HA tag and myc epitope and a PDGFR transmembrane domain in the C-terminal region, and was transfected into HEK293T cells for EVs isolation. The potency of NB60 E to knock down Trop2 in letrozole-resistant breast cancer cells (LTLT-Ca and MDA-MB-468 cells) was initially investigated. Thereafter, the effects of NB60 E on the cell viability and downstream signaling pathway of Trop2 via MTT assay and Western blotting were determined. Lastly, we also examined whether NB60 E treatment in Jurkat T cells affects IL-6, TNF-α, and IL-2 cytokine production by enzyme-linked immunosorbent assay (ELISA). Results: Results revealed treatment with NB60 E significantly reduced surface Trop2 expression across both cell lines by 23.5 ± 1.5% in MDA-MB-468, and 61.5 ± 1.5% in LTLT-Ca, relative to the HEK293T-derived control EVs (HEK293T E). NB60 E treatment resulted in a marked reduction in LTLT-Ca cell viability by 52.8 ± 0.9% at 48 h post-treatment. This was accompanied by downregulation of key oncogenic signaling molecules: phosphorylated ERK1/2 (p-ERK 1/2) decreased by 30 ± 4%, cyclin D1 by 67 ± 11%, phosphorylated STAT3 (p-STAT3) by 71.8 ± 1.6%, and vimentin by 40.8 ± 1.4%. ELISA analysis revealed significant decreases in IL-6 (−57.5 ± 1.5%, 7.4 ± 0.35 pg/mL) and TNF-α (−32.1 ± 0.3%, 6.1 ± 1.2 pg/mL) levels, coordinated by an increase in IL-2 secretion (22.1 ± 2.7%, 49.2 ± 1.1 pg/mL). Quantitative analysis showed marked reductions in the number of nodes (−45 ± 4.4%), junctions (−55 ± 3.5%), and branch points (−38 ± 1.2%), indicating suppression of angiogenic capacity. In vivo experiment using near-infrared Cy7 imaging demonstrated rapid and tumor-selective accumulation of NB60 E within 4 h post-administration, followed by efficient systemic clearance by 24 h. The in vivo results demonstrate the effectiveness of NB60 E in targeting Trop2-enriched tumors while being efficiently cleared from the system, thus minimizing off-target interactions with normal cells. Lastly, Trop2 expression in LTLT-Ca tumor xenografts revealed a significant reduction of 41.0 ± 4% following NB60 E treatment, confirming efficient targeted delivery. Conclusions: We present a first-in-field NB60 E-grafted EV therapy that precisely homes to Trop2-enriched breast cancers, silences multiple growth-and-invasion pathways, blocks angiogenesis, and rewires cytokine crosstalk, achieving potent antitumor effects with self-clearing, biomimetic carriers. Our results here show promising potential for the use of NB60 E as anti-cancer agents, not only for letrozole-resistant breast cancer but also for other Trop2-expressing cancers. Full article

Objectives: This study aimed to evaluate the effects of thymoquinone (TMQ) on metabolic, hormonal, and ovarian dysfunctions in a letrozole-induced polycystic ovary syndrome (PCOS) rat model and compare its efficacy with metformin, which is widely recognized as the first-line pharmacological treatment for PCOS. Methods: Thirty-two female Wistar Albino rats were randomly assigned into four groups: control (I), PCOS (II), PCOS + metformin (III), and PCOS + Thymoquinone (IV). PCOS was induced using 1 mg/kg/day letrozole for 21 days, followed by treatment with either metformin (500 mg/kg/day) or thymoquinone (50 mg/kg/day) for 30 days. Metabolic (glucose, insulin, HOMA-IR, lipid profile), hormonal (estrone, estradiol, testosterone, androstenedione), and histopathological parameters were assessed. Results: PCOS induction resulted in significant metabolic, hormonal, and ovarian dysfunctions. Final body weight was significantly higher in PCOS (309.0 ± 7.5 g) vs. control (275.3 ± 8.2 g, p < 0.001), but reduced by metformin (294.0 ± 7.4 g, p < 0.01) and thymoquinone (305.7 ± 7.5 g, p < 0.01). Glucose levels were significantly elevated in PCOS (341.8 ± 16.8 mg/dL) vs. control (260.0 ± 15.8 mg/dL, p < 0.01), while metformin (290.2 ± 19.7 mg/dL, p < 0.05) and thymoquinone (320.3 ± 13.7 mg/dL, p < 0.05) reduced glucose levels. Insulin and HOMA-IR were significantly increased in PCOS (p < 0.001), but reduced by both treatments (p < 0.01). Lipid profile improvements were observed, with significant reductions in TG and LDL-C and increases in HDL-C in both treatment groups (p < 0.05–0.01). PCOS induced hyperandrogenism, with increased testosterone and androstenedione (p < 0.05), and a decreased E2/E1 ratio (p < 0.001), which were significantly improved by metformin and thymoquinone (p < 0.01). Ovarian histopathology showed increased cystic and atretic follicles and reduced corpus luteum in PCOS (p < 0.05–0.01), which were significantly improved by both treatments. Conclusions: TMQ exerts metabolic, hormonal, and ovarian protective effects comparable to metformin, supporting its potential as a natural therapeutic alternative for PCOS management. Given that metformin is already established as a first-line pharmacological therapy, our findings suggest that TMQ may provide a promising complementary or alternative approach. Further clinical studies are warranted to evaluate its safety and efficacy in human PCOS patients. Full article

Background: Ectopic pregnancy (EP) is a serious condition often treated with methotrexate. Letrozole, a safer aromatase inhibitor, may offer an effective alternative. This study presents a meta-analysis comparing the efficacy and safety of single-agent letrozole versus methotrexate for EP management. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. Six sources of information underwent screening until 12 June 2025. Risk of bias and evidence certainty of evidence were assessed. Primary outcome was treatment success rate. Results were presented as mean difference (MD) or risk ratio (RR) along with a 95% confidence interval (CI) using a random-effects model. Results: Six studies (three randomized controlled trials and three nonrandomized prospective cohort studies) comprising seven arms and 260 patients (letrozole = 130, methotrexate = 130) were included. Almost all studies (n = 5) had overall moderate or high risk. Treatment success rates were comparable between groups (n = 7 arms; RR = 1.05; 95% CI: [0.94, 1.17]; p = 0.40). Letrozole was associated with significantly lower β-hCG levels on day 4 (n = 5 arms; MD = −95 mIU/mL; 95% CI: [−189.7, −0.91]; p = 0.048), day 7 (n = 5 arms; MD = −86.24 mIU/mL; 95% CI: [−143.1, −29.36]; p < 0.001), and day 14 (n = 3 arms; MD = −9.15 mIU/mL; 95% CI: [−17.24, −1.06]; p = 0.03); however, the differences were not clinically meaningful. Letrozole showed a better safety profile with higher platelet counts and lower liver enzymes. AMH levels were similar between groups. Most analyses were consistent, though secondary outcomes were less stable. Overall evidence certainty was rated ‘very low’ due to seriousness of risk of bias and imprecision. Conclusions: While letrozole shows comparable efficacy to methotrexate and a potentially better safety profile in the management of EP, the certainty of evidence is ‘very low’ due to risk of bias and imprecision. Therefore, these findings should be interpreted with caution, and further high-quality studies are urgently needed to confirm the results. Full article

Estrogens are hormones that play an important role in the skin, including in men. Letrozole (LET) is an inhibitor of the enzyme that converts androgens to estrogens. The use of letrozole can cause morphological changes and changes in the immunoexpression of proteins associated with oxidative stress and apoptosis. Vitamin C is a factor that modulates cellular stress. The purpose of this study was to examine whether letrozole and/or vitamin C supplementation can affect the morphology of the skin, parameters of the programmed cell death marker, and oxidative damage. Three-month-old rats were divided into four groups and treated with: (I) CTRL—water; (II) VIT C—L-ascorbic acid; (III) LET—letrozole; and (IV) LET+C—letrozole + L-ascorbic acid. The morphometrical measurements included epithelial thickness, width of collagen fibers, and elastic fibers. The expression levels of caspase-3 and catalase were determined. Significant differences in the morphometrical measurements and immunoexpression were observed. The findings indicate that chronic treatment with letrozole can affect morphology and induce oxidative stress and programmed cell death in the epidermal cells of adult male rats. Vitamin C supplementation exerts an effect on some parameters of the molecular processes. Full article

Current aftercare after early breast cancer overlooks recent evidence on circulating free tumor DNA (ctDNA). In this case report, we present a patient with low-risk hormone-receptor-positive breast cancer. ctDNA was first detected using a tumor-informed approach 12 months after the initial diagnosis and remained positive throughout adjuvant therapy with letrozole, while routine staging examinations showed no signs of relapse. Clinical relapse was ultimately identified nearly six years after the initial diagnosis, resulting in a lead time of four years and nine months. Current studies on ctDNA in the adjuvant setting have been conducted in high-risk cohorts and have shown a median molecular lead time of 8.9–12.4 months. Our study supports the need for large randomized clinical trials involving low-risk breast cancer patients to drive changes in clinical practice. Full article

Objectives: This study aimed to evaluate marjoram’s ameliorative effects in a letrozole-induced PCOS rat model and to explore its mechanism of action, focusing on Nrf2 activation and NF-κB suppression in ovarian tissue. Methods: In this study, PCOS was induced by the oral administration of letrozole (1 mg/kg/day) for 21 days. Rats were then divided into six groups: control (0.5% CMC), letrozole, letrozole + metformin (2 mg/100 g), and letrozole + MRJ extract (20, 40, or 60 mg/kg). All groups received oral treatment for 21 days. Biochemical analysis was performed using serum and plasma; while ovarian tissue homogenate was used for antioxidant enzymes and inflammatory and apoptosis biomarkers. Results: The letrozole-treated animals exhibited significant increases in final body weights, as well as ovary length and weight. In terms of biochemical parameters, there were significant increases in fasting blood glucose and insulin, HOMA-IR, and serum levels of cholesterol, triglycerides (TGs), and LDL-c and a decrease in HDL levels. Concerning the hormonal profile, testosterone and LH levels were significantly elevated while a notable decrease in FSH and estradiol levels was observed. Similarly, letrozole-treated rats showed significantly elevated levels of MDA and many other inflammatory mediators such as IL-6, TNF-α, and ICAM-1. A significant increase in the markers of intrinsic cell apoptosis, such as Bax and caspase-3, and the reduced levels of Bcl-2 and antioxidant mediators, including GSH, SOD, and HO-1, as well as mRNA and nuclear expression of Nrf2, compared to control rats, have been reported. The ovaries of the rats with PCOS treated with metformin and MRJ (60 mg/kg) showed the most significant improvements. Similarly, TEM also demonstrated a dose-dependent ameliorating effect. Conclusions: The current study highlights marjoram’s protective effect against letrozole-induced ovarian damage in rats with polycystic ovarian syndrome, suggesting its potential as a complementary and therapeutic agent for managing PCOS. Full article

Letrozole, a third-generation aromatase inhibitor initially developed for breast cancer, has become the preferred first-line agent for ovulation induction (OI), particularly in women with polycystic ovary syndrome (PCOS). This narrative review critically evaluates the efficacy, safety, and clinical applications of letrozole across diverse infertility contexts. Compared to clomiphene citrate, letrozole is associated with higher ovulation and live birth rates, a lower risk of multiple gestation, and a more favorable endometrial environment. Its pharmacokinetics—marked by transient estrogen suppression and a short half-life—limit embryonic exposure, supporting its favorable safety profile. Emerging data from large, randomized trials and meta-analyses demonstrate no increase in congenital anomalies, miscarriage, or adverse perinatal outcomes in letrozole-conceived pregnancies. Moreover, maternal side effects are generally mild, and the risk of ovarian hyperstimulation syndrome is low. Letrozole has also shown utility in mild stimulation protocols, fertility preservation for estrogen-sensitive malignancies, and clomiphene-resistant PCOS. Key clinical strategies—such as early-cycle initiation, lowest effective dosing, and individualized monitoring—optimize therapeutic outcomes while minimizing potential risks. While long-term offspring data remain limited and mechanistic concerns persist, current evidence robustly supports letrozole as a safe and effective option for OI, balancing reproductive success with maternal–fetal safety across a range of infertility indications. Full article

Fagonia cretica, a medicinal herb from the Zygophyllaceae family, is traditionally utilized to treat various conditions such as hepatitis, gynecological disorders, tumors, urinary tract issues, and diabetes. The present study aimed to evaluate the therapeutic potential of Fagonia cretica in treating polycystic ovarian syndrome (PCOS) induced in female rats. PCOS, a complex hormonal disorder, was experimentally induced by administering Letrozole (1 mg/kg) in combination with a high-fat diet for 21 days. The affected rats were then treated with hydro-alcoholic extracts of Fagonia cretica at doses of 100 mg/kg, 200 mg/kg, and 300 mg/kg for 20 days. Key biochemical parameters—including serum testosterone, insulin, fasting blood glucose, insulin resistance (HOMA-IR), cholesterol, triglycerides, and lipoprotein levels—were measured. Ultrasound imaging and histopathological analysis of ovarian tissues were also performed. The data were analyzed using computer-based statistical tools, including one-way ANOVA, Cohen’s d effect size, and Tukey’s HSD test, with graphical representations generated using Python 3.10 on the Kaggle platform. Results demonstrated a significant reduction in serum testosterone, insulin, cholesterol, and triglyceride levels (p < 0.05) in treated groups, along with improved ovarian morphology. These findings support the therapeutic potential of Fagonia cretica as a natural treatment for PCOS. Full article

Background and Objectives: The objective of this review is to evaluate the current evidence regarding hormone treatments for both premenopausal and postmenopausal women with early-stage hormone receptor (HR) positive breast cancer. Materials and Methods: An in-depth exploration of the existing literature was conducted, with landmark clinical trials such as TEXT, SOFT, ATLAS, and aTTom serving as primary references. Results: Through an extensive review of the literature, our findings indicate that for premenopausal women with HR-positive, HER2-negative BC with a low risk of recurrence, standard 5-year monotherapy with tamoxifen represents the optimal therapeutic management, given its favorable clinical outcomes and lower associated toxicity. In contrast, for premenopausal women with an intermediate to high risk of recurrence with the same tumor characteristics, the most effective approach stated in the literature is a combination of ovarian suppression therapy (chemical/surgical) and an aromatase inhibitor/selective estrogen receptor modulator (tamoxifen), with a possible extension of the standard therapeutic period. In postmenopausal patients with HR-positive, HER2-negative breast cancer with a low recurrence risk, the first line of treatment is usually a standard 5-year period of treatment with aromatase inhibitors (AIs)(letrozole, anastrozole, or exemestane). On the other hand, in postmenopausal women with an intermediate to high risk, combination therapy might be needed, as well as an extension of the standard therapeutic time. Conclusions: Treatment consensus depends on pre- vs. postmenopausal status and recurrence risk. Full article

Purpose: Neoadjuvant endocrine therapy (NET) represents a valuable treatment option for hormone receptor-positive (HR+)/HER2-negative breast cancer, particularly in postmenopausal women. This study aimed to evaluate the clinical and histopathological efficacy of NET and to explore early and late changes in Ki-67 and progesterone receptor (PgR) expression as indicators of endocrine response. Methods: A prospective cohort of 127 postmenopausal patients with stage cT1–4N0–3M0 HR+/HER2− breast cancer was enrolled between 2019 and 2021. Patients received NET (mostly letrozole) for a mean of 7.7 months. In 80 cases, a second core biopsy was performed after four weeks. Tumor size, histological grade, and biomarkers (Ki-67, PgR) were assessed pre- and post-treatment. Results: NET led to a significant reduction in tumor size, with median shrinkage of 47.0% (from 32.0 mm to 17.0 mm, p < 0.0001). Breast-conserving surgery (BCS) was performed in 52.2% of patients and lymph node negativity (pN0) was observed in 50.4%. Median Ki-67 decreased from 20.0% at baseline to 5.0% after four weeks (p < 0.0001) and remained low in surgical specimens (median 5.0%, p < 0.0001). In 33.3% of patients, Ki-67 dropped below 2.7%, and 67.0% showed a concordant decrease in both Ki-67 and PgR. PgR expression declined significantly during treatment (p < 0.0001). HER2 status conversion was noted in 6.4% of patients during treatment. Pathological complete response (pCR) occurred in 3.5%, while minimal or moderate residual disease (RCB I–II) was identified in 71.3% of cases. Conclusions: NET effectively reduced tumor burden and histological aggressiveness, enabling higher rates of BCS. Early reduction in Ki-67 and PgR may serve as surrogate markers of endocrine responsiveness, supporting their use for treatment stratification and monitoring during NET in HR+/HER2− breast cancer. Full article

Background: Infertility affects 8–12% of couples globally, with causes including hormonal and structural abnormalities. Letrozole, an aromatase inhibitor, is commonly used for ovulation induction, but its role in various assisted reproductive technologies (ARTs) and across different subgroups of infertile women remains unclear. Objective: This scoping review aimed to map the existing evidence on the use of letrozole in assisted reproductive cycles, focusing on reproductive outcomes and its application across different patient populations. Methods: A scoping review was conducted following the PRISMA-ScR guidelines. Twelve studies—including randomized controlled trials and retrospective cohorts—were identified through a structured search strategy. Studies comparing letrozole alone or in combination with gonadotropins/clomiphene to other stimulation protocols were included. Data were charted across multiple outcomes including oocyte yield, implantation, pregnancy, miscarriage, and live birth rates. Results: Evidence suggests that letrozole-based protocols may enhance oocyte yield and improve reproductive outcomes in certain settings. The highest implantation rate (57%) was observed in natural cycles, while the letrozole-only group showed the highest clinical pregnancy (50.57%) and live birth rates (45.58%). Combination protocols achieved the highest ongoing pregnancy rate (58.3%), with the lowest miscarriage rate (14.86%) in the letrozole-only group. Conclusions: Letrozole appears to be a versatile agent in ART, especially for patients requiring reduced gonadotropin doses or estradiol modulation. This scoping review highlights the need for further research to clarify its optimal use across different infertility subgroups and ART modalities. Full article

Polycystic ovary syndrome (PCOS) is the expression of a complex alteration of the reproductive system. It is characterised by the increase in androgens, causing symptoms such as hirsutism, as well as infertility in many. This paper reviews whether Clomiphene Citrate, Letrozole and Inositol function better as monotherapy or combined therapy for anovulatory infertile PCOS patients. Ovulation and pregnancy rate were used as primary outcomes. PubMed and Scopus were the search engines of choice. Papers were excluded if patients were undertaking other fertility interventions, overlapping populations and non-RCT papers. It was found that co-prescribing Letrozole or Clomiphene Citrate alongside Metformin should be considered, Inositol should be examined as an alternative insulin sensitiser to Metformin and studies should be undertaken to identify the ideal dose and duration of Inositol therapy. Further large, well-designed, multi-centre studies should be conducted to solidify the claims of this review. Full article

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disorder in reproductive-aged women, characterized by hyperandrogenism, oligoanovulation, and polycystic ovarian morphology. Despite its classification as a reproductive disorder, PCOS is closely associated with metabolic dysregulation, including insulin resistance and obesity. An ideal animal model for PCOS should replicate both reproductive and metabolic features of the condition. In this study, we compared two widely used postnatal PCOS models (letrozole and estradiol valerate [EV]) administered alone or in combination with a high-fat diet (HFD), assessing their ability to induce both the reproductive and metabolic features. Letrozole treatment led to significant weight gain and increased visceral adiposity, effects that were amplified by HFD. Conversely, EV treatment showed a tendency toward reduced body mass. While neither model significantly altered fasting glucose levels, letrozole combined with HFD impaired glucose tolerance, supporting its role in metabolic dysfunction. Hyperandrogenism was more consistently induced by letrozole compared to EV, aligning with clinical PCOS phenotypes. Both treatments disrupted estrous cyclicity and induced polycystic ovarian morphology, though metabolic disturbances were more pronounced in the letrozole model. These findings suggest that letrozole, particularly in combination with HFD, provides a more consistent model for studying both the reproductive and metabolic facets of PCOS. Full article