Search Results (239)

Background: Drug–drug interactions (DDIs) may occur when two or more drugs are taken together, leading to undesired side effects or potential synergistic effects. Most clinical effects of drug combinations have not been assessed in clinical trials. Therefore, predicting DDIs can provide better patient management, avoid drug combinations that can negatively affect patient care, and exploit potential synergistic combinations to improve current therapies in women’s healthcare. Methods: A DDI prediction model was built to describe relevant drug combinations affecting reproductive treatments. Approved drug features (chemical structure of drugs, side effects, targets, enzymes, carriers and transporters, pathways, protein–protein interactions, and interaction profile fingerprints) were obtained. A unified predictive score revealed unknown DDIs between reproductive and commonly used drugs and their associated clinical effects on reproductive health. The performance of the prediction model was validated using known DDIs. Results: This prediction model accurately predicted known interactions (AUROC = 0.9876) and identified 2991 new DDIs between 192 drugs used in different female reproductive conditions and other drugs used to treat unrelated conditions. These DDIs included 836 between drugs used for in vitro fertilization. Most new DDIs involved estradiol, acetaminophen, bupivacaine, risperidone, and follitropin. Follitropin, bupivacaine, and gonadorelin had the highest discovery rate (42%, 32%, and 25%, respectively). Some were expected to improve current therapies (n = 23), while others would cause harmful effects (n = 11). We also predicted twelve DDIs between oral contraceptives and HIV drugs that could compromise their efficacy. Conclusions: These results show the importance of DDI studies aimed at identifying those that might compromise or improve their efficacy, which could lead to personalizing female reproductive therapies. Full article

Endometriosis is a benign and often underdiagnosed condition that affects women of reproductive age, typically between 18 and 45 years. It can cause infertility and pain, including radicular pain and low back pain (LBP). The aim of this case report is to emphasize the importance of making a differential diagnosis when facing LBP and radicular symptoms. We report the case of a 17-year-old female patient, R.A., presented with a significant LBP (NPRS 8/10) radiating from her lumbar spine to her right buttock and occasionally to both legs, accompanied by weakness. She revealed exacerbation of pain during menstruation, despite being under hormonal contraceptive treatment. After three physiotherapy sessions that included education, manual therapy and exercise, the patient’s pain persisted so her physiotherapist recommended an evaluation in the emergency department, where standard radiography did not reveal any significant findings. Physiotherapy continued until the fifth session, when the patient agreed to undergo evaluation at a specialized endometriosis centre. Further investigations revealed endometriotic tissue on the uterosacral ligament, leading to hormonal therapy adjustment, with which pain gradually decreased to a manageable level (NPRS 2/10). This case report highlights the importance of an early differential diagnosis in patients with LBP, as endometriosis can present not only in older women but also in younger patients, including those already on oral contraceptives. Therefore, to mitigate the risk of pattern recognition bias, clinicians must maintain a high index of suspicion for endometriosis, even in atypical or unlikely clinical presentations. Full article

Endometriosis is the extrauterine engraftment of endometrium-like tissue, causing chronic pain. Complex sensory–vascular–immune interactions, including growth factors, cytokines, and neuropeptides, are implicated in its pathophysiology, but the mechanisms remain unknown. Here, epidermal growth factor (EGF), vascular endothelial growth factor, interleukins (IL-1β, IL-6, IL-8), macrophage migration inhibitory factor (MIF), calcitonin gene-related peptide, and somatostatin were measured in the serum of endometriosis patients with different disease severities, menstruation cycle- and pharmacotherapy-related hormonal status compared with controls. Mediator levels in deep-infiltrating rectosigmoid nodules were also compared with those in non-endometriotic colon tissues. Pain was assessed by the visual analogue scale. Serum EGF was significantly lower in mild endometriosis and in the secretory phase. MIF and IL-6 were higher in stage I–IV endometriosis, with MIF also higher in the secretory phase and in patients not receiving oral contraceptives. Somatostatin was lower in mild endometriosis than that in healthy individuals and the severe endometriosis group. No tissue-level differences were found. A strong positive correlation between serum EGF and somatostatin levels and dysmenorrhea and dysuria was detected in mild cases. It is concluded that certain serum alterations may be related to severity- and hormone status-dependent endometriosis mechanisms, but their diagnostic/prognostic value seems to be limited due to variability and lack of specificity. Full article

Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age, often requiring complex pharmacological management. The heterogeneity of the syndrome and the use of on- and off-label therapeutic agents—ranging from insulin sensitizers and ovulation inducers to oral contraceptives and herbal supplements—pose significant challenges, including adverse effects, drug interactions, and poor adherence. This narrative review explores the role of pharmacists in identifying and mitigating drug-related problems (DRPs) associated with PCOS therapy. Through thematic synthesis of the current literature, the study highlights common DRPs such as suboptimal drug selection, inappropriate dosing, prolonged therapy duration, and treatment-related safety concerns. It underscores the value of pharmacists’ interventions in enhancing medication adherence, optimizing therapeutic regimens, providing patient education, and monitoring adverse events. A structured, patient-level pharmaceutical care model is proposed, emphasizing personalized assessment, interdisciplinary collaboration, and continuous follow-up. The integration of clinical pharmacists into PCOS care teams has the potential to improve treatment effectiveness, patient satisfaction, and long-term health outcomes. Pharmacists’ contributions are especially critical given the widespread use of off-label therapies and supplements with variable evidence of benefit. Tailored pharmaceutical care can thus bridge the existing gaps in PCOS management and enhance the quality of life for the affected individuals. Full article

Objectives: In the context of the global rise in antimicrobial resistance (AMR), this study aimed to investigate temporal trends in AMR among pathogens isolated from endometrial cultures of patients diagnosed with chronic endometritis (CE). Methods: This cross-sectional study included 244 women consecutively diagnosed with CE at the Gynecology Unit of the University of Bari, Italy, between January 2020 and June 2024. Exclusion criteria were (i) previous CE diagnosis or treatment; (ii) antimicrobial use in the month prior to hysteroscopy and biopsy; (iii) use of oral or vaginal prebiotics/probiotics or contraceptives in the three months prior; (iv) known immunosuppression; and (v) hypersensitivity to quinolones or macrolides. CE was diagnosed using hysteroscopy combined with endometrial histology and microbial culture. Specifically, in cases with hysteroscopic signs suggestive of CE, endometrial biopsies were obtained using a Novak curette and processed for histological and immunohistochemical analyses, as well as for microbial identification and antimicrobial susceptibility testing in accordance with EUCAST guidelines. The primary outcomes were the prevalence of CE-associated pathogens and their AMR profiles. Results: The median age at CE diagnosis was 33 years (range 26–44). The most frequently isolated pathogens were Enterococcus faecalis (26.2%), Escherichia coli (19.3%), and Ureaplasma urealyticum (16.4%). High AMR rates were observed, with increasing trends over time. Ampicillin resistance reached 98.5% (63/64), penicillin resistance 30.8% (16/52), and extended-spectrum beta-lactamase (ESBL) positivity 34.7% (25/72), all with statistically significant trends (p < 0.001). Resistance to commonly used first-line antimicrobials, such as tetracyclines, quinolones, and nitroimidazoles, was also substantial. Conclusions: This study highlights a significant increase in AMRs among microorganisms responsible for CE between 2020 and 2024. As a result, empirical first-line antimicrobial therapies commonly used to treat patients with CE may be increasingly ineffective in a growing number of cases. This underscores the need for improved and targeted diagnostic and therapeutic strategies to effectively manage CE and prevent treatment failures. Strengthening surveillance systems, implementing antimicrobial stewardship programs, and enhancing patient education may help counter the growing threat of AMR. Full article

Background/Objectives: Worldwide, men experience a higher incidence of pancreatic cancer (PC) than women. Methods: To increase understanding of the underlying reasons for this sex-related difference, we analysed general and sex-related risk factors for PC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (women/men No. = 293,682/136,728; 717/577 PC-cases). Results: Cox proportional hazards models showed a 1.31-fold higher risk of developing PC for men compared to women (HR, 95% CI 1.15–1.49) after adjustment for age, smoking history, BMI, diabetes, and alcohol consumption. Associations of PC with established risk factors did not differ between men and women, with the exception of a greater risk of PC among women with greater attained body height, meat consumption and cigarettes smoked (1.12 (1.05–1.19) per 5 cm, 1.18 (1.02–1.36) per 100 g/d, 1.42 (1.27–1.59) per 10/d; respectively). Among child-bearing women, long cumulative duration of breastfeeding was inversely associated with risk of PC (HR 0.74, 95% CI 0.61–0.89) for >5.7 months of breastfeeding (median) relative to ≤5.7 months and among HRT users, cumulative duration of HRT use was inversely associated with PC risk (HR 0.71, 95% CI 0.53–0.95, >2.4 versus ≤2.4 years). Further reproductive and hormonal factors, such as age at menarche, number of full-term pregnancies, age at menopause, or use of oral contraceptives, were not significantly associated with PC risk. Conclusions: Pooled analyses of large cohort studies are needed to confirm these results, and detailed data on the type and intensity of HRT are required to better evaluate its effect. Full article

Endometriosis is a chronic inflammatory disease characterized by the presence of ectopic endometrial tissue, mainly in the pelvic cavity. It primarily affects women of reproductive age and is associated with significant morbidity, particularly chronic pelvic pain and infertility. Despite its high prevalence, diagnosis is often delayed, contributing to prolonged suffering and increased healthcare burden. This review examines the management of endometriosis in Primary Care, focusing on clinical presentation, risk factors, diagnostic approaches, and therapeutic options. A comprehensive bibliographic search was conducted using PubMed, Scopus, and Uptodate, including evidence-based clinical guidelines and literature up to January 2025. Women diagnosed with endometriosis in Primary Care are typically of reproductive age, with symptoms including dysmenorrhea, dyspareunia, and abnormal uterine bleeding. Risk factors include early menarche, low birth weight, short menstrual cycles, and family history. Transvaginal ultrasound is the recommended first-line imaging tool. Treatment includes analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), and hormonal therapies such as combined oral contraceptives or progestins. Non-pharmacological interventions, including dietary modifications and psychological support, are also relevant. Early identification in Primary Care is key to improving out-comes. Enhancing awareness among healthcare providers and promoting multidisciplinary management are essential to optimize care and reduce diagnostic delays. Full article

Background/Objectives: Using healthcare vouchers mitigates the financial burdens of low-income individuals, therefore enhancing mothers’ satisfaction and encouraging service utilization. In Yemen, reducing financial barriers results in marked improvement in reproductive health services utilization for mothers and their newborns. Such financial strain can be addressed through reproductive health vouchers, which reduce out-of-pocket expenses of family planning, pregnancy, birth, postnatal care and neonatal care. This study compares the Safe Motherhood and Family Planning Voucher Program in the Lahj governorate to the non-voucher program in the Abyan governorate in terms of enhancement of reproductive healthcare accessibility and use. Methods: This facility-based, quantitative, comparative, cross-sectional study was conducted in the Lahj governorate, which supports the Safe Motherhood and Family Planning Voucher Program, and the Abyan governorate, which does not. Results: The voucher-supported program has greatly improved mothers’ satisfaction, access, and use of all reproductive health services by covering transportation, covering lodging during hospitalization, and providing free reproductive treatments. Compared to Abyan mothers, Lahj governorate mothers more frequently used rental vehicles (paid for by the voucher program) and free reproductive health services (p-value < 0.001). Lahj governorate mothers (who used the vouchers) used family planning, prenatal care, facility-based delivery, home delivery by competent birth staff, cesarean section, postnatal care, and neonatal care more frequently than Abyan governorate mothers. A health institution which supported the Safe Motherhood and Family Planning Voucher Program (SMHFPVP) provided prenatal care (98.5%), competent birth services (99.0%), and modern contraceptive use (92.3%)—oral contraceptive pills, implants, injectables, contraceptive patches, vaginal rings, and intrauterine devices—for mothers who were interviewed and attended the targeted HFs in the Lahj governorate, compared with (77.6%), (80.3%), and (67.8%), respectively, for mothers in Abyan governorate who were not supported by the SMHFPVP. This study demonstrates substantially higher satisfaction levels among voucher-using mothers in the Lahj governorate compared to those in the Abyan governorate, across all satisfaction domains and overall satisfaction scores. Conclusions: This study found that women without access to maternal health vouchers experienced worse prenatal, natal, and postnatal care and were less satisfied with healthcare services compared with women who used vouchers. Full article

The heart rate variability (HRV), influenced by female sex hormone fluctuations, is an indicator of athletes’ adaptation. This case study explores HRV responses over 18 months across a natural menstrual cycle (MC) and during oral contraceptive (OC) use in two Olympic female swimmers. HRV measurements—including mean heart rate (HR); root mean square of successive differences (RMSSD); and frequency-domain indices—were collected at rest in supine (SU) and standing (ST) positions across two competitive seasons. Nocturnal HR and RMSSD were assessed using the Ōura^® ring. MC and OC phases were identified through specific tracking, and training load was controlled. In both athletes, resting HR was lower during bleeding phases, increasing from menstruation to the luteal phase (MC) and from withdrawal to active pill phases (OC). In the ST position, RMSSD was higher but decreased throughout the phases. Nocturnal measurements confirmed these trends. Overall, findings suggest a phase-related parasympathetic overactivity shift. This study provides novel insights into HRV responses across hormonal cycles in elite female athletes, which present unique characteristics. Such monitoring tools may support a data-informed approach to guide and periodize training more effectively. Full article

Polycystic ovary syndrome (PCOS) is a complex endocrine disease. This study investigates the relationship between endothelial function, insulin resistance, and hormonal profiles in women with PCOS. Forty women with PCOS were included: metformin (n = 20), GLP1-RAs (n = 10), and oral contraceptive pills (n = 10). A 75 g oral glucose tolerance test (OGTT) was performed, and the 0, 60, and 120 min insulin, glucose, and endothelial functions were evaluated. The postprandial and fasting state Matsuda Index and HOMA Index were measured. All measurements were performed at baseline and at a 6-month follow-up. At baseline, the percentage change in the Perfused Boundary Region (PBR) was associated with the percentage change in glucose at 120 min of the OGTT (r = 0.42, p < 0.05). The Matsuda Index, Homa Index, and testosterone levels were associated with the PBR (2.91 ± 0.1 μm) at 120 min of the OGTT (r = 0.41, r = 0.38 and r = 0.28, respectively). MMP9 levels were associated with the Matsuda and Homa Index (r = 0.45, p < 0.05 and r = 0.41, p < 0.05, respectively). At the 6-month follow-up, all the participants presented improvements of the Matsuda Index (7 ± 0.31 vs. 9.1 ± 0.2), Homa Index (5.3 ± 0.8 vs. 2.91 ± 0.1), MMP9 (210 ± 30 vs. 178 ± 28 ng/mL), and testosterone levels (44.2 ± 5 vs. 39.1 ± 2 ng/dL) compared to the baseline (p < 0.05 for all the comparisons). Patients who received GLP1-RA agonists presented the greatest improvement in MMP9 levels. Postprandial hyperglycemia, insulin resistance, and testosterone levels are associated with an impaired glycocalyx thickness in women with PCOS. Full article

Background: The relationship between oral contraceptive (OC) use and pancreatic cancer (PC) risk remains controversial, with inconsistent findings reported in observational studies. To clarify this relationship and better identify potential risk factors for PC prevention, more unbiased and robust approaches are needed. Methods: We investigated the potential causal relationship between OC use and PC risk using a two-sample Mendelian randomization (MR) analysis, with blood protein quantitative trait loci (pQTLs) as instrumental variables. To ensure the robustness of our findings, we performed a series of sensitivity analyses, colocalization analyses, and reverse MR. The causal effects of protein-coding genes on PC risk, as well as their expression patterns across different single-cell types, were subsequently investigated. To elucidate the potential pathogenic pathways, we conducted pathway enrichment analysis, protein–protein interaction (PPI) network analysis, and causal inference. Results: Our MR analysis identified five drug-targeted proteins significantly associated with PC risk. Higher levels of COMT, AGT, FN1, and UGT1A1, as well as lower levels of SERPINC1, were associated with an increased risk of PC. Among these, AGT, FN1, and COMT demonstrated consistent associations across sensitivity analyses and downstream analyses, providing robust evidence supporting their involvement in PC risk. Conclusions: This study provides genetic evidence suggesting, in European groups, a potential causal link between OC use and increased PC risk, possibly mediated through drug-targeted proteins such as AGT and FN1. These results highlight the importance for further research to elucidate the underlying mechanisms and assess the implications of OC use on PC risk. Full article

Background/Objectives: Acne vulgaris is a chronic skin infection characterized by high sebum secretion, keratosis around hair follicles, inflammation, and imbalance in androgen levels. Acne vulgaris causes permanent scars or skin pigmentation in cases of improper treatment. Oral or topical isotretinoin, contraceptives, and antibiotics are used to treat acne. Minocycline is one of the widely used tetracyclines for this purpose; it inhibits the synthesis of proteins in bacterial ribosomes. Commonly, minocycline is prescribed daily for several months for acne vulgaris. Systemic minocycline is highly distributed into body fluids, and it is associated with several side effects and antibiotic resistance. Additionally, minocycline is highly metabolized in the liver, leading to reduced bioavailability upon systemic delivery. This study aims to develop and characterize minocycline nanocrystals for targeted skin delivery and evaluate their antimicrobial efficacy in treating acne vulgaris. Methods: Minocycline nanocrystals were synthesized using milling or solvent evaporation techniques. Nanocrystals were characterized in terms of particle size, particle distribution index (PDI), zeta potential, and morphology. The antibacterial efficacy against Propionibacterium acne, Staphylococcus aureus, and Staphylococcus epidermidis was evaluated using a minimum inhibitory concentration assay (MIC) and agar well diffusion test in comparison to coarse minocycline. Results: Minocycline nanocrystals had a particle size of 147.4 ± 7.8 nm and 0.27 ± 0.017 of PDI. The nanocrystals exhibited a loading efficiency of 86.19 ± 16.7%. Antimicrobial testing showed no significant difference in activity between minocycline and its nanoparticle formulation. In terms of skin deposition, the nanocrystals were able to deliver minocycline topically to rat skin significantly more than free minocycline. The nanocrystal solution deposited 554.56 ± 24.13 μg of minocycline into rat skin, whereas free minocycline solution deposited 373.99 ± 23.32 μg. Conclusions: Minocycline nanocrystals represent a promising strategy for targeted skin delivery in the treatment of acne vulgaris, potentially reducing systemic side effects and antibiotic resistance and improving patient outcomes. Full article

This systematic review aims to evaluate the impact of hormonal fluctuations during the menstrual cycle on the performance of female athletes. Methods: Following PRISMA guidelines, a comprehensive search was conducted in Scopus, Web of Science, and PubMed databases using the keywords: (“Menstrual cycle”) AND (“performance” OR “female athlete” OR “sport” AND NOT “male”); AND NOT (“contraceptive”). Inclusion criteria focused on original studies published between 2013 and 2023, in English or Spanish, involving eumenorrheic female athletes without menstrual disorders or oral contraceptive use. The studies were critically assessed using the McMaster scientific review method. Results: Thirteen eligible articles were reviewed, comprising a total sample of 152 athletes. Significant findings include increased flexibility during the ovulatory phase and enhanced aerobic and anaerobic capacities in the luteal phase. Additionally, the menstrual and premenstrual phases notably influenced aerobic and anaerobic capacities, performance perception, symptomatology, and exercise-induced muscle damage. Conclusion: Hormonal fluctuations can impact female athletes’ performance. However, further research is warranted due to inconsistent results stemming from variations in cycle phases studied, lack of standardized methodologies, small sample sizes, and short observation periods. Full article

Background: Isotretinoin is a highly effective treatment for moderate-to-severe acne, but strict contraceptive measures are required because of its teratogenicity. The European Pregnancy Prevention Programme (PPP) aims to minimise foetal exposure through structured protocols. However, real-world data on patient compliance and treatment outcomes are limited. Methods: This retrospective study included 569 female patients aged 14–25 years treated with isotretinoin in Poland (2021–2022). Patients were assigned to three groups based on PPP compliance: full (Group I), partial (Group IIA), and minimal (Group IIB). Data on contraception, cumulative dose, treatment duration, adverse events, laboratory monitoring, and therapy discontinuation were analysed using non-parametric statistical tests (p < 0.05). Results: No pregnancies occurred during treatment. Overall compliance with PPP requirements was high: 100% of the patients used contraception or declared abstinence. The majority (92.79%) used condoms, 1.93% used oral contraceptives, and 7.21% reported abstinence. Significant differences in cumulative isotretinoin dose were observed between the groups (Kruskal–Wallis H = 19.89, p < 0.001), with Group I receiving a lower mean dose than those in Groups IIA (p < 0.001) and IIB (p < 0.01). Notably, all therapy discontinuations (4.75%) occurred in Group I (full compliance), which may reflect stricter monitoring and an earlier identification of adverse effects or patient concerns. These discontinuations were associated with lower cumulative dosing (Mann–Whitney Z = 7.81, p < 0.001) than that seen in the other groups. An inverse correlation between age and cumulative dose was also found (H = 13.09, p = 0.0004), with younger patients (≤17 years) more likely to reach therapeutic targets. Conclusions: Isotretinoin therapy under structured PPP protocols is safe and effective, with no pregnancies reported and excellent contraceptive compliance. Significant differences in dosing and adherence patterns highlight the need for flexible patient-centred approaches to optimise safety and outcomes. Full article

SHBG is a glycoprotein that not only controls serum sex hormone levels but is also strongly correlated with metabolic syndrome, cardiovascular risk, thyroid function, gynecological conditions, and even the process of carcinogenesis. Synthesis of SHBG is controlled by many factors related to obesity, lipogenesis, inflammatory status, and genetic predisposition. By influencing the bioavailability of sex hormones, SHBG regulates their effects not only on the reproductive system, but also cardiomyocytes, vascular epithelium, and more. In this review, we aim to gather and summarize current knowledge on the physiology of SHBG and its association with cardiovascular disease, metabolic syndrome, DM 2, thyroid function, PCOS, hypogonadism, infertility, and its correlations with oral contraception. What is more, genetic alterations are mentioned to highlight SHBG as a potential new diagnostic marker. Furthermore, we assess the clinical usefulness of this parameter in the diagnosis and treatment of patients suffering from the above-specified conditions. Full article