Effects of Physical Activity at High Altitude on Hormonal Profiles in Foreign Trekkers and Indigenous Nepalese Porters.

Altitude exposure affects hormonal homeostasis, but the adaptation of different populations is still not finely defined. This study aims to compare the mid-term effects of combining physical activity and altitude hypoxia on hormonal profiles in foreign trekkers coming from Italy versus indigenous Nepalese porters during a Himalayan trek. Participants (6 Italians and 6 Nepalese) completed a 300 km distance in 19 days of an accumulated altitude difference of 16,000 m, with an average daily walk of 6 h. The effect of high altitude on hormonal pathways was assessed by collecting blood samples the day before the expedition and the day after its completion. Foreign trekkers had an additional follow-up sample collected after 10 days. The findings revealed a different adaptation of thyroidal and gonadal axes to mid-term strenuous physical activity combined with high-altitude hypobaric hypoxia. The thyroid function shifted to the protective mechanism of low free triiodothyronine (FT3), whereas the gonadal axis was suppressed. The Italian trekkers and Nepalese porters had lower total testosterone and 17-ß-estradiol levels after the expedition. At the follow-up, the Italians had increased testosterone values. Prolactin secretion decreased in the Italians but increased in the Nepalese. We conclude that exposure to high-altitude affects the hormonal axes. The effect seems notably pronounced for the hypothalamus-pituitary gonadal axis, suppressed after high-altitude exposure.

Can Tangier disease cause male infertility? A case report and an overview on genetic causes of male infertility and hormonal axis involved.

Tangier disease is an autosomal recessive disorder caused by mutations in the ABCA1 gene and characterized by the accumulation of cholesteryl ester in various tissues and a near absence of high-density lipoprotein. The subject in this investigation was a 36-year-old Italian man with Tangier disease. He and his wife had come to the In Vitro Fertilization Unit, Pesaro Hospital (Azienda Ospedaliera Ospedali Riuniti Marche Nord) seeking help regarding fertility issues. The man was diagnosed with severe oligoasthenoteratozoospermia. Testosterone is the sex hormone necessary for spermatogenesis and cholesterol is its precursor; hence, we hypothesized that the characteristic cholesterol deficiency in Tangier disease patients could compromise their fertility. The aim of the study was to therefore to determine if there is an association between Tangier disease and male infertility. After excluding viral, infectious, genetic and anatomical causes of the subject's oligoasthenoteratozoospermia, we performed a hormonal analysis to verify our hypothesis. The patient was found to be negative for frequent bacteria and viruses. The subject showed a normal male karyotype and tested negative for Yq microdeletions and Cystic Fibrosis Transmembrane Conductance Regulator gene mutations. A complete urological examination was performed, and primary hypogonadism was also excluded. Conversely, hormonal analyses showed that the subject had a high level of follicle stimulating hormone and luteinizing hormone, low total testosterone and a significant decline in inhibin B. We believe that the abnormally low cholesterol levels typically found in subjects with Tangier disease may result in a reduced testosterone production which in turn could affect the hormonal axis responsible for spermatogenesis leading to a defective maturation of spermatozoa.

Postoperative Hormonal Outcomes in Patients with Large and Giant Non-functioning Pituitary Adenomas.

OBJECTIVE AND AIMS: To study hormonal axis (HA) dysfunction pre-operatively and at three months after surgery in patients with large (>3 cms) (Hardy's grade C) and giant (>4 cms) nonfunctioning pituitary adenomas (NFPA). METHODS: One hundred thirty nine patients operated between 2006 and 2017, with 3 months post-operative hormonal evaluation, were included in this retrospective study. HA damage was categorized as 0 to 3 based on number of axes (thyrotroph, corticotroph and gonadotroph) that were affected. Risk factors studied for HA dysfunction before and after surgery included duration of symptoms, size of tumor, diabetes mellitus, hypertension and extent of resection. RESULTS: Preoperatively 45 (32.3%) had no axis involvement, 34 (24.4%), 36 (25.8%) and 24 (17.2%) had one, two and three axes involvement respectively. Thyrotroph axis was affected in most patients. Tumor volume had significant correlation with preoperative pituitary dysfunction (P < 0.000). Post-operatively HA function remained same in 100 (72%), improved in only 7 (5%) and worsened in 32 (23%) of the patients. Of the 3 HA, corticotroph function worsened in most patients. None of the patients who had dysfunction in all three axes had improvement after surgery. No significant risk factors were associated with post-operative pituitary function outcomes. Persistent diabetes insipidus was noted in six (4.3%) patients. CONCLUSION: Pre-operatively anterior pituitary dysfunction is noted in nearly two-thirds of patients with large and giant NFA. Tumor volume >15 cc had significant correlation with pre-operative panhypopituitarism. Post-operatively, pituitary function remains the same in nearly three quarters of the patients. No significant risk factors were found for post-operative hormonal outcomes.

Effects of bleomycin, etoposide and cisplatin treatment on Leydig cell structure and transcription of steroidogenic enzymes in rat testis.

Cytotoxic anticancer chemotherapy affects pituitary-testicular hormonal axis in humans and in animals. This study investigated the effects on Leydig cells of three cycles of bleomycin, etoposide and cisplatin (0.75, 7.5, and 1.5mg/kg, respectively; BEP) chemotherapy in rat testis. The chemotherapy has induced hyperplasia of and degenerative changes in Leydig cells at the end of BEP exposure, which remained so even after a recovery time of 63 days. The increased testicular oxidative stress at the end of the chemotherapy returned to normal level after the recovery time. The chemotherapy has stimulated the transcription of scavenger receptor class type-B1 (SCARB1), steroidogenic acute-regulatory protein (StAR), cytochrome P450 cholesterol side-chain cleavage (CYP11A1), CYP17A1, and inhibited that of 17ß-hydroxysteroid dehydrogenase (HSD17B6) and CYP19A1 in association with increased cholesterol and decreased testosterone levels. Even after the recovery time, the chemotherapy still had inhibitory effects on the transcription of all of the above genes in addition to luteinizing hormone receptor and HSD3B1, but not on the StAR gene. The cholesterol and testosterone levels also did not show any significant differences with the control group. The decreased testosterone level at the end of chemotherapy was probably due to inhibition of HSD3B1 and HSD17B6 genes. In conclusion, clinically relevant dose-levels and treatment protocols of BEP chemotherapy adversely affect Leydig cell function. The BEP chemotherapy inhibits the transcription of steroidogenic enzymes and that these effects sustain over an extended period of time without returning to normal levels.