Search Results (159)

Background: Optimizing pregnancy outcomes while minimizing gonadotropin exposure and treatment burden remains a major goal in ovulation induction for intrauterine insemination (IUI), particularly for patients with polycystic ovary syndrome (PCOS) or high ovarian reserve. Sequential protocols combining early letrozole with late-onset recombinant FSH (rFSH) have been proposed to enhance efficiency while reducing medication requirements. However, real-world comparative data adjusting for baseline differences are limited. Methods: This retrospective comparative cohort study included 764 IUI cycles performed between January 2022 and October 2025. Cycles were stimulated either with conventional rFSH (n = 372) or letrozole plus late-onset rFSH (n = 392). The primary outcome was pregnancy per cycle, defined by a positive serum β-hCG. Secondary outcomes included clinical pregnancy, total gonadotropin dose, endometrial thickness, cycle cancelation, and obstetric outcomes. Confounding was addressed using multivariable logistic regression, propensity score matching (PSM), inverse probability of treatment weighting (IPTW), and doubly robust estimation. Results: The crude pregnancy rate was higher in the letrozole plus late rFSH group compared with conventional rFSH (14.8% vs. 9.9%, p = 0.042). Women in the sequential stimulation group had higher AMH levels, higher antral follicle counts, and a higher prevalence of PCOS (32.4% vs. 16.3%, p = 0.001). After adjustment for age, ovarian reserve, and other baseline characteristics using regression, PSM, and IPTW, the stimulation protocol was not independently associated with pregnancy (adjusted OR 1.09, 95% CI 0.68–1.74; p = 0.657). Female age remained the strongest predictor of pregnancy (adjusted OR 0.70 per year increase; p < 0.001). The sequential protocol required a significantly lower total gonadotropin dose (median 375 IU vs. 750 IU; p < 0.001) while maintaining comparable cycle cancellation and safety outcomes. Conclusions: Sequential stimulation with letrozole plus late-onset rFSH achieves pregnancy outcomes comparable to conventional rFSH stimulation while significantly reducing gonadotropin requirements. After adjustment for PCOS status and ovarian reserve, the protocol itself did not independently influence pregnancy, suggesting that crude differences reflected baseline imbalances rather than true treatment effects. This approach represents a clinically efficient, gonadotropin-sparing option for IUI, particularly in patients at risk for excessive ovarian response. Full article

Background/Objectives: Breast cancer is the most common cancer and the second leading cause of cancer death in women. The aromatase enzyme plays a role in estrogen biosynthesis and is an important biological target for breast cancer treatment. For this purpose, some new 1,3,4-thiadiazole (4a–4j) and 1,2,4-triazole (5a–5j) structures were designed and synthesized based on the structures of the existing aromatase inhibitors letrozole and anastrozole. Methods: The antiproliferative activities of the compounds were tested against MCF-7 cancer cells. The NIH3T3 healthy cells were used to evaluate the selectivity of the compounds. The inhibitory activities of all compounds were tested against the aromatase enzyme. Results: The 1,2,4-triazole derivatives 5b, 5c, 5e, 5f and 5g exhibited the highest antiproliferative activity against MCF7 cells with IC₅₀ values ranging from 3.142 to 10.415 μM. Similar to the antiproliferative activity results, triazole derivatives 5b, 5c, 5e, 5f and 5g exhibited comparable anti-aromatase activity to letrozole (IC₅₀ = 0.031 μM) with IC₅₀ values ranging from 0.064 to 2.224 μM and demonstrated the highest anti-aromatase activity within the series. The interactions of compound 5c, the most potent compound based on activity results, with the aromatase enzyme have been elucidated through molecular docking and MD simulation studies. Conclusions: According to experimental studies and molecular docking findings, compound 5c shows promise for further studies with its aromatase enzyme inhibitory potential. Full article

Invasive lobular carcinoma (ILC) accounts for approximately 15% of breast cancers and the most common neoplasm in the female population. Cervical involvement is exceptionally rare and often underrecognized. This relationship is well-defined in the context of breast and ovarian cancer syndrome related to BRCA gene mutations. However, it is also observed in rare but underreported cases of cervical metastases originating from breast cancer. The objective of this manuscript is to describe a rare case of cervical recurrence of invasive lobular carcinoma and summarize comparable case to guide future gynecologic follow-up strategies. Therefore, we report the case of a 60-year-old woman who developed a late cervical recurrence of ILC ten years after her initial breast cancer diagnosis. The patient had previously undergone mastectomy for ER-positive, PR-positive, HER2-negative ILC, followed by five years of adjuvant endocrine therapy. She remained disease-free until presenting with post-menopausal bleeding, urinary symptoms, and acute renal failure. Pelvic examination and ultrasonography revealed an enlarged, indurated cervix with bilateral hydroureteronephrosis. Biopsy demonstrated a discohesive infiltrate consistent with metastatic lobular carcinoma, confirmed by immunohistochemistry (GATA3+, CK7+, ER/PR+, E-cadherin−, CK20−, CDX2−). Staging PET-CT showed additional metastases involving bone, peritoneum, and lymph nodes. The patient began systemic therapy with ribociclib plus letrozole, achieving radiologic improvement of the cervical lesion and abdominal disease. After a follow-up of several months, she maintains stable disease but has persistent chronic renal impairment secondary to obstructive uropathy. This case highlights the ability of ILC to recur after long latency and to metastasize to unusual gynecologic sites such as the cervix. We also review the literature on cervical recurrence from lobular carcinoma to emphasize the importance of gynecologic surveillance in breast cancer survivors and to identify areas that require further investigation. Full article

Follicle-stimulating hormone receptor (FSHR) is expressed on the plasma membrane of granulosa cells in the ovarian follicles. FSHR is involved in the development and maturation of Graafian follicles, along with granulosa proliferation and estrogen synthesis. There are two well-characterized non-synonymous single-nucleotide gene polymorphisms in the exon 10 of the human FSHR gene, namely rs6165 (c.919G>A, Ala307Thr) and rs6166 (c.2039A>G, Ser680Asn). Recent research clarifies the association of rs6165/rs6166 with susceptibility to infertility-associated ovarian diseases, ranging from polycystic ovarian syndrome, premature ovarian insufficiency, endometriosis, to ovarian cancer, along with response/resistance to ovulation induction/ovarian stimulation with clomiphene citrate, letrozole, metformin, FSH preparations, and adjunctive growth hormone in infertility treatment. This narrative review aims to update the knowledge on the relationship among rs6165/rs6166, infertility etiology, and differential responses to oral ovulation induction agents, FSH preparations, and adjunctive growth hormone. The re6165/rs6166 genotype-guided choice of individualized ovulation stimulation preparations has great potential to reduce unexpected poor or high ovarian responses in ovulation induction and ovarian stimulation and improve clinical outcomes in reproductive medicine. Current evidence is insufficient, and further studies are warranted to ascertain its potential for clinical implementation. Full article

Objective: To systematically analyze and synthesize the evidence from the literature, we compared outcomes of the PPOS + LE protocol versus standard PPOS in patients undergoing IVF. Materials and Methods: We systematically searched the MEDLINE, Scopus, EMBASE, and Science Citation Index databases to identify relevant studies. The clinical questions were developed according to the PICO framework. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale. Primary outcomes were ovarian stimulation outcomes (oocyte retrieved and mature oocytes). Secondary outcomes were hormonal levels during COS and pregnancy outcome. Results: Five retrospective studies compared oocyte yields between the PPOS and PPOS + LE protocols across diverse populations. While some authors reported significantly higher numbers of retrieved and mature oocytes with letrozole co-administration in a normal infertile population and in POSEIDON group 4, others found no benefit in the PCOS or POSEIDON 3 groups, indicating variable efficacy depending on patient characteristics. Conclusions: Incorporating letrozole counteracts the intense pituitary suppression typically associated with standard PPOS, increasing LH levels and the number of retrieved and mature oocytes in normal and poor responders, but not in PCOS women. Retrospective data do not allow for definitive conclusions to be drawn. Further studies are needed to confirm these results. Full article

Background/Objectives: Aromatase inhibitors (AIs)—specifically, letrozole, anastrozole and exemestane—represent the current gold standard for patients with estrogen-receptor-positive breast cancer (ER + BC). This narrative review highlights potential interactions between nutrients and AIs, elucidating their molecular mechanisms involved. Methods: A comprehensive search was conducted across the PubMed, ScienceDirect, Google Scholar, and Scopus databases to identify scientific publications and elucidate recommended dietary regimes for ER + BC patients treated with AIs. Results: Certain bioactive substances found in licorice, rosemary, juniper, cannabis, and citrus fruits exhibit intrinsic aromatase-inhibiting effects. Additionally, other nutrients and compounds—including honey, ginger, turmeric, sweet potatoes, pomegranates, bitter melon, dark sweet cherries, resveratrol, and vitamins D and C—contribute to treatment outcomes through their demonstrated antiproliferative properties. Certain natural compounds, such as soy, cow’s milk, sesame seeds, and sesame oil, require caution due to their potential estrogen-like effects which could diminish the anti-estrogenic efficacy of AIs. Conclusions: These considerations hold significant weight in this context, as the management of oncological patients—particularly women with ER + BC—requires an integrated perspective. Antineoplastic treatment must be supported by appropriate nutrition to enhance antitumor efficacy and improve the patient’s quality of life. The data presented herein are derived from in vitro, in silico, and animal model studies and await validation in large patient cohorts. Nevertheless, these findings pave the way for future research to elucidate these molecular phenomena in humans and to establish clinically significant conclusions for ER + BC patients. Full article

Introduction: We previously showed that baboon offspring born to mothers deprived of estrogen during the second half of gestation exhibited insulin resistance prior to and after the onset of puberty. Moreover, the size of skeletal muscle myofibers and the number of microvessels important for delivery of insulin/glucose to myofibers were lower in near-term fetuses deprived of estrogen during pregnancy, and myofiber capillarization remained reduced in post-pubertal offspring deprived of estrogen in utero. However, it remains to be determined whether skeletal muscle size is restored to normal in animals deprived of estrogen in utero after the onset of puberty/gonadal estrogen production. Methods: To answer this question, the current study quantified the size and number of slow and fast fibers in biopsies of vastus lateralis skeletal muscle obtained from post-pubertal female baboon offspring 9–12 years old, born to mothers who were untreated (n = 7) or treated during the second half of gestation with letrozole (n = 6; suppressed maternal and fetal estrogen by >90%) or letrozole plus estradiol benzoate (n = 3). Results: Results indicated that skeletal muscle slow and fast fiber growth in female offspring appeared to occur by hypertrophy and that respective size of fibers after the onset of puberty was similar in offspring born to mothers who were untreated or deprived of estrogen in utero. Conclusions: Postnatal myofiber hypertrophy likely reflects the impact of the pubertal surge in and continued exposure of offspring myofibers to ovarian estrogen and is restored to normal in post-pubertal female offspring deprived of estrogen in utero. Full article

Online adaptive radiotherapy mitigates errors in absorbed dose delivery due to daily anatomical changes during hypofractionated breast treatment, particularly when comprehensive nodal therapy includes the internal mammary chain. To illustrate this, we present a case of a 65-year-old woman with left-sided luminal B invasive carcinoma, who underwent segmentectomy and level 1–2 dissection. Pathology revealed an 18 × 15 × 13 mm primary tumor with lymphovascular invasion, two of eleven axillary nodes positive, and intramammary metastasis, staged pT1cN1a. She received adjuvant docetaxel–cyclophosphamide followed by letrozole. Hypofractionated radiotherapy (40 Gy in 15 fractions) was administered in an inspiration breath-hold setting using a CBCT-guided online-adaptive platform. Adaptive planning improved V95% coverage over the planned treatment for all targets: on average, whole breast coverage increased from 88.4% to 96.3%, supraclavicular from 93.0% to 97.1%, axilla from 90.6% to 96.7%, and internal mammary from 91.8% to 95.9%. Organ-at-risk metrics remained within limits: the mean heart dose increased slightly (from an average of 0.12 Gy in scheduled to 0.15 Gy in adaptive plans). At the same time, the LAD D0.03 cm³ decreased, and the heart V4 Gy fell modestly (from 13.3% in the scheduled plan to 8.2% in the adaptive plan), reflecting low-dose redistribution without exceeding constraints. Lung and thyroid mean doses remained comparable. The patient tolerated treatment well, with no acute toxicity or local recurrence. This case highlights the importance of daily adaptation for complex left-sided radiation treatment involving internal mammary nodes, demonstrating target recovery without exceeding absorbed dose constraints and supporting future studies on control, toxicity, and quality of life. Full article

Background/Objectives: The development of effective oncologic therapies with fewer adverse effects is often limited by the intrinsic and acquired resistance of tumor cells. Hybrid molecules, rationally designed to combine different pharmacophores, represent a promising strategy by providing synergistic effects, dose reduction, and a lower risk of resistance. In this study, the antitumor potential and mechanisms of action of 22 novel hybrid compounds derived from xanthene and pyran scaffolds (SJ022–SJ103) were investigated. The hybrids were initially evaluated through in vitro screening in four breast, three ovarian, and two prostate cancer cell lines, followed by the selection of T-47D, OVCAR-3, and LNCaP cells for detailed assays assessing cytotoxicity, apoptosis, cell cycle distribution, DNA damage, caspase-3/7 activity, morphology, and PI3K/AKT/mTOR pathway modulation. Methods: Cytotoxicity assays were performed in the selected cell lines, while mechanistic studies included apoptosis and cell cycle analysis by flow cytometry, γH2AX detection, Western blotting for PI3K/AKT/mTOR pathway proteins, and 3D spheroid assays. Combinatorial effects with hormone therapies (tamoxifen, fulvestrant, and letrozole) and the AKT inhibitor MK2206 were evaluated. AKT silencing by esiRNA and molecular docking was performed to confirm target engagement. Results: SJ028 demonstrated broad activity across all tested cell lines, whereas SJ064 and SJ078 exhibited higher selectivity. Treatments induced apoptosis, S/G2-M arrest, and DNA damage, accompanied by decreased phospho-AKT levels and stable PI3K and mTOR expression. In 3D models, the hybrids increased caspase-3/7 activity and necrotic core expansion. Co-administration with hormone therapies resulted in synergistic effects in breast and ovarian cancer cells, reducing IC₅₀ values by more than 50% in both parental and resistant models, while combinations with MK2206 were antagonistic across all tumor subtypes. AKT silencing abrogated cytotoxicity, and docking confirmed SJ028 binding to AKT. Conclusions: Xanthene- and pyran-based hybrids—particularly SJ028, SJ064, and SJ078—showed strong antitumor activity through apoptosis induction, cell cycle arrest, and PI3K/AKT pathway modulation. Their preserved efficacy in resistant models and synergistic interactions with hormone therapies contrasted with the antagonism observed with AKT inhibition, highlighting their potential as promising candidates for the treatment of hormone-responsive and -resistant cancers. Full article

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