Is Maternal Use of Paracetamol during Pregnancy Associated with Anogenital Distance in Male Newborns? The Results from the NELA Birth Cohort

Paracetamol is the one of the most commonly used medications during pregnancy. However, its potential antiandrogenic effect has been suggested. The objective of this study was to evaluate associations between maternal paracetamol use during pregnancy and anogenital distance (AGD) in male newborns from a Spanish birth cohort. The study included two hundred and seventy-seven mother-male child pairs with self-reported paracetamol use and frequency during each trimester of pregnancy. AGD measurements were taken employing standardized methods. The associations between maternal paracetamol use and AGD measures were evaluated using linear regression models, adjusting for potential confounders and covariates. Overall, 61.7% of pregnant women consumed paracetamol at any time of pregnancy with an average of 9.43 (SD = 15.33) days throughout pregnancy. No associations between the maternal use of paracetamol or its frequency and AGD measures among different trimesters or during the whole pregnancy were found in the adjusted final models. A non-differential misclassification error may have occurred—the recall of paracetamol intake independent of AGD measurements—introducing bias towards the null hypothesis. Nevertheless, the current evidence suggests that paracetamol might have a potential antiandrogenic effect especially in the early stages of fetal development. Thus, it would be highly recommendable to pursue further studies to elucidate the potential effects of paracetamol in human perinatal health and its use among pregnant women.

Flutamide Induced Liver Injury in Female Patients

Flutamide is the active substance of the drug and belongs to the group of drugs that have antiandrogenic effect. Flutamide prevents the action of male sex hormones, i.e. suppresses the action of testosterone and dihydrotestosterone. Primarily, the indications for the use of flutamide refer to males and the treatment of advanced prostate cancer. It is also used in the treatment of patients with testicles surgically removed, and in patients who have not responded to another type of therapy or do not tolerate other types of treatment. The efficacy of flutamide has also been proven in the treatment of acne, hirsutism and alopecia in men and women with polycystic ovaries. It is important to emphasize that flutamide can cause severe side effects, above all liver damage, so it is not justified to use it in the treatment of conditions other than prostate cancer. Numerous data on hepatotoxicity (retrospective, prospective studies, case reports, surveillance study) were available in literature, which ranged from asymptomatic to acute, fulminant hepatitis that ended in transplantation, i.e. fatal outcome. In our paper, a review of the literature with case reports of notably hepatotoxicity is presented along with a case from our clinical practice.

Menopausal hormone treatments and risk of cardiovascular diseases: modern view

Estrogens have a multifactorial protective effect on various components of the cardiovascular system, and postmenopause in women is associated with an increased incidence of cardiovascular disease. Admission of menopausal hormone therapy helps to reduce the risk of cardiovascular events, but the perceived benefit far outweighs the risks in cases where women begin treatment no later than at the age of 60 or 10 years after menopause. Studies have shown that the combination of estradiol and drospirenone is effective and safe in terms of preventing cardiovascular diseases. The antiandrogenic effect of drospirenone has additional metabolic effects that may be preferable in certain groups of postmenopausal patients.

p,p′-DDE Induces Apoptosis of Rat Sertoli Cells via a FasL-Dependent Pathway

One,1-dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p′-DDE), the major metabolite of 2,2-bis(4-Chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p′-DDE exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in p,p′-DDE-induced toxicity in male reproductive system. The results indicated that p,p′-DDE exposure at over 30 μM showed the induction of apoptotic cell death. p,p′-DDE could induce increases in FasL mRNA and protein, which could be blocked by an antioxidant agent, N-acetyl-l-cysteine (NAC). In addition, caspase-3 and -8 were activated by p,p′-DDE treatment in these cells. The activation of NF-κB was enhanced with the increase of p,p′-DDE dose. Taken together, these results suggested that exposure to p,p′-DDE might induce apoptosis of rat Sertoli cells through a FasL-dependent pathway.