Search Results (22)

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

Male hormonal contraception has been the focus of extensive research efforts aimed at identifying effective and reversible methods for male fertility control. This review summarizes the current state of knowledge, key achievements, and future directions in the development of male hormonal contraception. A review was conducted using the PubMed, Embase, and Scopus databases. The search strategy included terms such as “male hormonal contraception”, “Nestorone”, “7α,11β-Dimethyl-19-nortestosterone 17β-undecanoate (DMAU)” and “11β-methyl-19-nortestosterone 17β-dodecylcarbonate (11β-MNTDC)”. A total of 107 references were analyzed to synthesize the most relevant findings regarding the hormonal contraceptive agents under investigation. The review outlines historical and recent advancements in male hormonal contraception, highlighting compounds that have demonstrated limitations in effectiveness, side effects, or inconvenient administration. Notable candidates under study include 7α-methyl-19-nortestosterone (MENT), DMAU, 11β-MNTDC, and the combination of segesterone acetate with testosterone in gel form. These agents show promise due to their ability to suppress follicle-stimulating hormone (FSH) and luteinizing hormone (LH), leading to effective spermatogenesis inhibition with minimal side effects. Additionally, the phenomenon of spermatogenic rebound is considered. Among the investigated agents, oral DMAU, 11β-MNTDC, and the Nestorone–testosterone gel appear to be the most promising candidates for male hormonal contraception due to their high efficacy, user-friendly administration, and favorable safety profiles. However, further large-scale clinical trials are necessary to confirm their long-term effects on human health and fertility, ensuring their viability as future contraceptive options. Full article

Background/Objectives: Achilles and hamstring tendinopathies are common injuries in runners, and extracorporeal shockwave therapy (ESWT) may be an effective treatment. Runners are at risk for lower extremity tendinopathies and the Male and Female Athlete Triad (Triad). The purpose of this study is to evaluate the association of sex, exposure to hormonal contraceptives, menopause, and Triad-related risk factors with ESWT outcomes in the treatment of Achilles and hamstring tendinopathy. Methods: This is a retrospective cohort study of runners with either Achilles or hamstring tendinopathy who received radial or combined radial and focused ESWT. Tendon function was measured using Victorian Institute of Sport Assessment (VISA) questionnaires completed before and following treatment. Treatment success was defined by a change in VISA score that met the minimal clinically important difference (MCID). Results: There were 88 runners (54.5% female, 45.5% male) with Achilles (52.3%) or hamstring (47.7%) tendinopathy. No measurable difference was found in the proportion of females and males overall that achieved the MCID (57.1% and 72.5%, p = 0.17). Similar rates of females and males met MCID for Achilles (77.8% and 75.0%, p = 0.83) and hamstring tendinopathy (46.7% and 66.7%, p = 0.24). However, females with Achilles or hamstring tendinopathy who used oral contraceptive pills (OCPs) were less likely to meet the MCID compared to females not on OCPs (p = 0.031); this finding was present in a subgroup analysis of runners with only Achilles tendinopathy (p = 0.025). No associations were found between achieving the MCID and Triad risk factors, including body mass index, energy availability, weight-related behaviors, bone health, or menstrual function (all p > 0.05). Conclusions: Female and male runners reported similar success rates for ESWT, and Triad risk factors were not found to impact outcomes. However, females who used oral contraceptive pills were less likely to achieve the MCID from ESWT. Full article

11β-Methyl-19-nortestosterone dodecylcarbonate (11β-MNTDC) is a prodrug of 11β-MNT and is being considered as a promising male oral contraceptive candidate in clinical development. However, the oral administration of 11β-MNTDC exhibits an ~200-fold lower serum concentration of 11β-MNT compared to 11β-MNTDC, resulting in the poor bioavailability of 11β-MNT. To elucidate the role of the first-pass metabolism of 11β-MNT in its poor bioavailability, we determined the biotransformation products of 11β-MNT and its prodrugs in human in vitro models. 11β-MNT and its two prodrugs 11β-MNTDC and 11β-MNT undecanoate (11β-MNTU) were incubated in cryopreserved human hepatocytes (HHs) and subjected to liquid chromatography–high resolution tandem mass spectrometry analysis, which identified ten 11β-MNT biotransformation products with dehydrogenated and glucuronidation (11β-MNTG) metabolites being the major metabolites. However, 11β-MNTG formation is highly variable and prevalent in human intestinal S9 fractions. A reaction phenotyping study of 11β-MNT using thirteen recombinant UDP-glucuronosyltransferase (UGT) enzymes confirmed the major role of UGT2B17 in 11β-MNTG formation. This was further supported by a strong correlation (R² > 0.78) between 11β-MNTG and UGT2B17 abundance in human intestinal microsomes, human liver microsomes, and HH systems. These results suggest that 11β-MNT and its prodrugs are rapidly metabolized to 11β-MNTG by the highly polymorphic intestinal UGT2B17, which may explain the poor and variable bioavailability of the drug. Full article

Background: Injuries of the patellar tendon commonly occur as a result of mechanical loading of the tendon during physical activity. Shear wave elastography (SWE) is an established technique for assessing tendon stiffness, and has good interindividual reliability. The aim of this study was to investigate the impacts of physical parameters and different sports on patellar tendon stiffness in professional athletes using SWE. Methods: Standardized patellar tendon SWE was performed in a relaxed supine position with a small roll under the knee (20° flexion) in 60 healthy professional athletes (30 female, 30 male). Multiple linear regression was performed for patellar tendon stiffness including gender, age, body mass index (BMI), and type of sport. Results: Patellar tendon stiffness showed no significant difference between female (3.320 m/s) and male (3.416 m/s) professional athletes. Mean age (female: 20.53 years; male: 19.80 years) and BMI (female: 23.24 kg/m²; male: 23.52 kg/m²) were comparable. Female professional athletes with oral contraceptive (OC) intake showed higher patellar tendon stiffness than athletes without OC intake (3.723 versus 3.017; p = 0.053), but not significantly. Conclusion: In professional athletes, there are no significant differences in patellar tendon stiffness according to gender, age, BMI and type of sport (handball, volleyball, soccer, sprint, hammer throw). Oral contraceptives may not have an impact on patellar tendon stiffness in female athletes. Further studies are necessary. Full article

Trimethylamine N-oxide (TMAO), a gut-derived metabolite and marker of gut dysbiosis, has been linked to hypertension. Blood pressure is proposed to be elevated in hormonal contraceptive users and males compared to age-matched eumenorrheic females, but the extent to which TMAO differs between these populations has yet to be investigated. Peripheral and central blood pressure were measured, with the latter determined via applanation tonometry, and plasma TMAO concentration was assessed using liquid chromatography–tandem mass spectrometry. The following variables were assessed on two occasions in each of the following conditions: the early follicular phase (EFP) and mid-luteal phase (MLP) in eumenorrheic women (n = 13), and the pill-free interval (INACTIVE) and pill consumption days (ACTIVE) in women using oral contraceptive pills (n = 12), and in men (n = 22). Briefly, 17-β-estradiol and progesterone concentrations were quantified via ELISA in all females. There were no differences in TMAO concentration between EFP (2.9 ± 1.7 μmol/L) and MLP (3.2 ± 1.1 μmol/L), between INACTIVE (3.3 ± 2.9 μmol/L) and ACTIVE (2.3 ± 1.1 μmol/L) days, or between men (3.0 ± 1.8 μmol/L), eumenorrheic women (3.0 ± 1.3 μmol/L) and contraceptive users (2.8 ± 1.4 μmol/L). Blood pressure was consistent across the menstrual cycle and pill days, but brachial systolic blood pressure was higher in males than females. There were no differences in brachial diastolic blood pressure or central blood pressure between the sexes. Repeated measures of TMAO, blood pressure, 17-β-estradiol and progesterone were consistent in all populations. These findings suggest that the link between TMAO and blood pressure is limited in healthy young adults. Full article

Background: Systemic steroids, such as prednisone, hormonal replacement therapies, or oral contraceptives, are commonly prescribed to women who might also be receiving dental implant therapy. However, the effect of these medications on dental implant survival is unknown. Methods: The medical and dental records of individuals with dental implants (N = 1480 implants) who visited a postgraduate periodontics clinic between 2000 and 2017 were initially considered. Those younger than 21 years old, pregnant, or male were excluded according to the study’s exclusion criteria. The presence of systemic diseases and conditions was assessed. Implant failure rates among female patients using systemic steroids, hormone replacement therapy, or oral contraceptives were compared with failure rates among patients not taking those medications. Results: The implant failure rate for the 65 implants in patients taking steroid medications was 7.69%; the failure rate for the 712 implants in patients not taking steroids was 1.54% (p < 0.001). After adjusting for smoking and the presence of diabetes, that relationship persisted, with an 8.47% implant failure rate for the 59 implants in patients taking steroids (vs. 1.54% failure for the 585 implants in patients not taking steroids; p < 0.001). Regression analyses demonstrated that the odds of implant failure versus success were 5.31 times greater in patients taking systemic steroids, hormone replacement therapy, or oral contraceptives (p < 0.05). No statistically significant differences in patient plaque control were found between the experimental and control groups. Conclusions: Among women, the use of systemic steroids is associated with a five-fold increase in the rate of dental implant failure, regardless of the presence of smoking or diabetes. Full article

Background: Data from population-based studies investigating trends in environmental factors associated with inflammatory bowel disease (IBD) is lacking. We aimed to assess long-term time trends of environmental and socioeconomic factors in IBD patients from a well-defined population-based cohort from Veszprem, Hungary. Methods: Patients were included between 1 January 1977, and 31 December 2020. Trends of environmental and socioeconomic factors were evaluated in three periods based on the decade of diagnosis, representing different therapeutic eras: cohort-A,1977–1995; cohort-B,1996–2008 (immunomodulator era); and cohort-C, 2009–2020 (biological era). Results: A total of 2240 incident patients with IBD were included (ulcerative colitis (UC) 61.2%, male 51.2%, median age at diagnosis: 35 years (IQR 29–49)). Rates of active smoking significantly decreased over time in Crohn’s disease (CD): 60.2%, 49.9%, and 38.6% in cohorts A/B/C (p < 0.001). In UC, the rates were low and stable: 15.4%, 15.4%, and 14.5% in cohorts A/B/C (p = 0.981). Oral contraceptive use was more common in CD compared to UC (25.0% vs. 11.6%, p < 0.001). In UC, prevalence of appendectomy before diagnosis decreased over time: 6.4%, 5.5%, and 2.3% in cohorts A/B/C (p = 0.013). No significant changes were found in the socio-geographic characteristics of the IBD population (urban living: UC, 59.8%/64.8%/ 62.5% (p = 0.309) and CD, 62.5%/ 62.0%/ 59.0% (p = 0.636), in cohorts A/B/C). A greater percentage of patients had completed secondary school as the highest education level in later cohorts in both UC (42.9%/50.2%/51.6%, p < 0.001) and CD (49.2%/51.7%/59.5%, p = 0.002). A higher percentage of skilled workers (34.4%/36.2%/38.9%, p = 0.027) was found in UC, but not in CD (p = 0.454). Conclusion: The association between trends of known environmental factors and IBD is complex. Smoking has become less prevalent in CD, but no other major changes occurred in socioeconomic factors over the last four decades that could explain the sharp increase in IBD incidence. Full article

Various complications of pituitary neuroendocrine tumors (PitNET) are reported, and an intratumor hemorrhage or infarct underlying pituitary apoplexy (PA) represents an uncommon, yet potentially life-threatening, feature, and thus early recognition and prompt intervention are important. Our purpose is to overview PA from clinical presentation to management and outcome. This is a narrative review of the English-language, PubMed-based original articles from 2012 to 2022 concerning PA, with the exception of pregnancy- and COVID-19-associated PA, and non-spontaneous PA (prior specific therapy for PitNET). We identified 194 original papers including 1452 patients with PA (926 males, 525 females, and one transgender male; a male-to-female ratio of 1.76; mean age at PA diagnostic of 50.52 years, the youngest being 9, the oldest being 85). Clinical presentation included severe headache in the majority of cases (but some exceptions are registered, as well); neuro-ophthalmic panel with nausea and vomiting, meningism, and cerebral ischemia; respectively, decreased visual acuity to complete blindness in two cases; visual field defects: hemianopia, cranial nerve palsies manifesting as diplopia in the majority, followed by ptosis and ophthalmoplegia (most frequent cranial nerve affected was the oculomotor nerve, and, rarely, abducens and trochlear); proptosis (N = 2 cases). Risk factors are high blood pressure followed by diabetes mellitus as the main elements. Qualitative analysis also pointed out infections, trauma, hematologic conditions (thrombocytopenia, polycythemia), Takotsubo cardiomyopathy, and T3 thyrotoxicosis. Iatrogenic elements may be classified into three main categories: medication, diagnostic tests and techniques, and surgical procedures. The first group is dominated by anticoagulant and antiplatelet drugs; additionally, at a low level of statistical evidence, we mention androgen deprivation therapy for prostate cancer, chemotherapy, thyroxine therapy, oral contraceptives, and phosphodiesterase 5 inhibitors. The second category includes a dexamethasone suppression test, clomiphene use, combined endocrine stimulation tests, and a regadenoson myocardial perfusion scan. The third category involves major surgery, laparoscopic surgery, coronary artery bypass surgery, mitral valvuloplasty, endonasal surgery, and lumbar fusion surgery in a prone position. PA in PitNETs still represents a challenging condition requiring a multidisciplinary team from first presentation to short- and long-term management. Controversies involve the specific panel of risk factors and adequate protocols with concern to neurosurgical decisions and their timing versus conservative approach. The present decade-based analysis, to our knowledge the largest so far on published cases, confirms a lack of unanimous approach and criteria of intervention, a large panel of circumstantial events, and potential triggers with different levels of statistical significance, in addition to a heterogeneous clinical picture (if any, as seen in subacute PA) and a spectrum of evolution that varies from spontaneous remission and control of PitNET-associated hormonal excess to exitus. Awareness is mandatory. A total of 25 cohorts have been published so far with more than 10 PA cases/studies, whereas the largest cohorts enrolled around 100 patients. Further studies are necessary. Full article

Venous thromboembolism (VTE) is the third most common cause of death worldwide. The incidence of VTE varies according to different countries, ranging from 1–2 per 1000 person-years in Western Countries, while it is lower in Eastern Countries (<1 per 1000 person-years). Many risk factors have been identified in patients developing VTE, but the relative contribution of each risk factor to thrombotic risk, as well as pathogenetic mechanisms, have not been fully described. Herewith, we provide a comprehensive review of the most common risk factors for VTE, including male sex, diabetes, obesity, smoking, Factor V Leiden, Prothrombin G20210A Gene Mutation, Plasminogen Activator Inhibitor-1, oral contraceptives and hormonal replacement, long-haul flight, residual venous thrombosis, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, trauma and fractures, pregnancy, immobilization, antiphospholipid syndrome, surgery and cancer. Regarding the latter, the incidence of VTE seems highest in pancreatic, liver and non-small cells lung cancer (>70 per 1000 person-years) and lowest in breast, melanoma and prostate cancer (<20 per 1000 person-years). In this comprehensive review, we summarized the prevalence of different risk factors for VTE and the potential molecular mechanisms/pathogenetic mediators leading to VTE. Full article

Cenerimod, a sphingosine-1-phosphate 1 receptor modulator, is in development for the treatment of systemic lupus erythematosus, a disease mainly affecting women of childbearing potential. The effect of cenerimod on the pharmacokinetics (PK) of a combined oral contraceptive (COC, 100 µg levonorgestrel and 20 µg ethinylestradiol (EE)) was investigated. A randomized, double-blind, parallel-group study was performed in 24 healthy male and female subjects. A single oral dose of COC was administered alone and after 35 days of once daily (o.d.) administration of cenerimod 0.5 (n = 10) or 4 (n = 14) mg. Exposure to EE alone or in combination with cenerimod was comparable as reflected by the geometric mean ratios and the respective 90% confidence intervals, while a slight increase in exposure (approximately 10–25%) to levonorgestrel was observed at clinically relevant concentrations of cenerimod. Overall, COC alone or in combination with cenerimod was safe and well tolerated. Two subjects reported one adverse event each (one headache after COC alone, and gastroenteritis in combination with cenerimod 4 mg). In conclusion, cenerimod does not affect the PK of levonorgestrel or EE to a clinically relevant extent. Therefore, COC can be selected as method of contraception during and after cenerimod therapy without the risk of interaction. Full article

The use of medicinal plants for contraception remains a common practice among South African ethnic groups. The present study assessed the phytochemical profile, cytotoxicity, acute oral toxicity and efficacy of a herbal mixture used for contraception by the Batswana of South Africa. An aqueous extract was prepared from equal quantities (in terms of weight) of Bulbine frutescens (roots), Helichrysum caespititium (leaves) and Teucrium trifidum (leaves) based on a recipe used by traditional health practitioners. The phytochemical profiles of the freeze-dried herbal mixture were analyzed using gas chromatography–mass spectrometry (GC-MS). In addition, cytotoxicity was determined using an MTT assay on Vero cells and in vivo contraceptive efficacy was evaluated using seven Sprague Dawley rats per control and treatment groups. The control group received distilled water while test groups received 5, 50 and 300 mg/kg of the herbal mixture, which was administered orally once a day for three consecutive days. Subsequently, female rats were paired 1:1 with males for 3 days. Their weights were measured weekly and incidence of pregnancy was recorded. The GC-MS chromatogram revealed the presence of 12 identified and 9 unidentified compounds. In terms of safety, the herbal mixture had an IC₅₀ value of 755.2 μg/mL and 2000 mg/kg, which was the highest tested dose that caused no mortality or morbidity in the rats. A contraceptive efficacy of 14.5% was exerted with 50 mg/kg herbal mixture extract while other doses had no effects given that all the rats were pregnant. Based on a chi-square test (p < 0.05), there was no correlation between the tested herbal mixture doses and contraception, nor on the weight of the rats. Overall, the herbal mixture extract was found to be safe but had limited contraceptive efficacy at the tested doses. In future studies, exploring increased dose range, solvent extract types and hormonal analysis will be pertinent. Full article

Cerebral venous thrombosis accounts for 0.5–1% of all cerebrovascular events and is one type of stroke that affects the veins and cerebral sinuses. Females are more affected than males, as they may have risk factors, such as pregnancy, first period after pregnancy, treatment with oral contraceptives treatment with hormonal replacement, or hereditary thrombophilia. This neurological pathology may endanger a patient’s life. However, it must be suspected in its acute phase, when it presents with variable clinical characteristics, so that special treatment can be initiated to achieve a favorable outcome with partial or complete functional recovery. The case study describes the data and the treatment of two patients with confirmed cerebral venous thrombosis with various localizations and associated risk factors, who were admitted to the neurology department of the Sf. Apostol Andrei Emergency Hospital in Constanta. The first patient was 40 years old and affected by sigmoid sinus and right lateral sinus thrombosis, inferior sagittal sinus, and right sinus thrombosis, associated with right temporal subacute cortical and subcortical hemorrhage, which appeared following a voluntary abortion. The second case was a patient aged 25 who was affected by left parietal cortical vein thrombosis, associated with ipsilateral superior parietal subcortical venous infarction, which appeared following labor. The data are strictly observational and offer a perspective on clinical manifestations and clinical and paraclinical investigations, including the treatment of young patients who had been diagnosed with cerebral venous thrombosis and admitted to the neurology department. Full article

Hepatocellular carcinoma (HCC) is a male-oriented malignancy; its progression is affected by sex hormones. 17α-ethinylestradiol (EE2) is a synthetic estrogen widely used as an oral contraceptive; however, it is unknown whether EE2 regulates sex hormone action in HCC. We investigated whether EE2 influences HCC risk in male androgenic environments, using mice expressing human sex hormone-binding globulin (SHBG). Two-week-old male mice were injected with diethyl-nitrosamine (DEN, 25 mg/kg) and fed an EE2 diet for 10 weeks from 30 weeks of age. Development and characteristics of liver cancer were evaluated in 40-week-old mice via molecular and histological analyses. Although EE2 did not increase HCC progression in wild-type mice, SHBG mice exhibited remarkably higher HCC risk when fed EE2. The livers of EE2-treated SHBG mice exhibited substantially increased pro-inflammatory necrosis with high plasma levels of ALT and HMGB1, and intrahepatic injury and fibers. Additionally, increased androgen response and androgen-mediated proliferation in the livers of EE2-treated SHBG mice and EE2-exposed hepatocytes under SHBG conditions were observed. As a competitor of SHBG-androgen binding, EE2 could bind with SHBG and increase the bioavailability of androgen. Our results revealed that EE2 is a novel risk factor in androgen-dominant men, predisposing them to HCC risk. Full article

To prevent unwanted pregnancies, oral emergency contraception (EC) with the active ingredients levonorgestrel (LNG) and ulipristal acetate (UPA) is recommended by the guidelines of the German Federal Chamber of Pharmacists (BAK). In this respect, community pharmacies (CPs) in Germany have a major responsibility for information gathering, selecting the appropriate medicine, availability and pricing, among other things. Therefore, it would be appropriate to conduct a study with the aim of investigating information gathering, a possible recommendation as well as availability and pricing for oral EC in German CPs. A representative nationwide observational study based on the simulated patient methodology (SPM) in the form of covert mystery calls will be conducted in a random sample of German CPs stratified according to the 16 federal states. Each selected CP will be randomly called once successfully by one of six both female and male trained mystery callers (MCs). The MCs will simulate a product-based scenario using the request for oral EC. For quality assurance of the data collection, a second observer accompanying the MC is planned. After all mystery calls have been made, each CP will receive written, pharmacy-specific performance feedback. The only national SPM study on oral EC to date has identified deficits in the provision of self-medication consultations with the help of visits in the CPs studied. International studies suggest that UPA in particular is not always available. Significant price differences could be found analogous to another German study for a different indication. Full article