Bone mineral metabolism and different indices of skeletal health of Ladakhi women living at high altitude.

Objectives: High altitude possesses a great challenge for human survival owing to low oxygen tension and has been reported to cause bone deterioration among sojourns of high altitude. The bone health of Ladakhi women is investigated for the first time in this study. Methods: Dual energy X-ray absorptiometry of Ladakhi women and sea level women was done at the radius and calcaneus using EXA-3000 (Osteosys, Korea), followed by colorimetric and Enzyme Linked Immunosorbent Assay analysis of parameters regulating bone health. Results: There was no statistically significant difference between bone mineral density of Ladakhi women and sea level women at radius (P = 0.287) or calcaneus (P = 0.839). Almost similar cases of osteopenia were reported at both sites measured in the study among both groups. Two post-menopausal Ladakhi women however, had osteoporosis at the radius while 4 had osteoporosis at calcaneus. Significant increase in calcium levels with a decrease in intact parathyroid hormone and an increase in calcitonin levels were observed in Ladakhi women as compared to sea level women. Though there was no significant difference in 25-hydroxy vitamin D levels of both groups, a higher percentage of 25-hydroxy vitamin D deficiency (77% vs 23%) was observed in Ladakhi women as compared to sea level women. Estradiol levels were similar in both groups. Conclusions: The present study suggest that there is no significant relationship between high altitude living and bone mineral density among Ladakhi women.

Anti-Mullerian Hormone and Macrophage Migration Inhibitory Factor Determine the Reproductive Health of Ladakhi Women Residing at 3,500 m.

Shaw, Snigdha, Himashree Gidugu, Gopinath Bhaumik, Maramreddy Prasanna Kumar Reddy, Usha Panjwani, and Dishari Ghosh. Anti-Mullerian hormone and macrophage migration inhibitory factor determine the reproductive health of Ladakhi women residing at 3,500 m. High Alt Med Biol. 22:317-326, 2021. Background: Reproductive health of Ladakhi high-altitude (HA) native females was investigated for the first time in this study. Available literature suggest that, female reproductive cycle and hormonal profile varies in different HA populations due to heterogeneity. Although these studies illustrate some progress on the role of HA hypoxia, it still leaves scope for evaluation of the remaining mechanisms involved in the maintenance of reproductive health in this contemporary population. Materials and Methods: Menstrual details, phasic variations in circulatory steroid hormones, and gonadotropins along with oxytocin in sea level (SL) and HA (∼3,500 m) native females of India were assessed. Moreover, ovarian reserve marker anti-Mullerian hormone (AMH) and proinflammatory cytokine macrophage migration inhibitory factor (MIF) were measured. Results: A difference in Ladakhi women was registered compared to SL, regarding luteinizing hormone (LH) (2.6 mIU/ml vs. 4.4 mIU/ml, p < 0.05) and progesterone (P) (4.1 ng/ml vs. 9.4 ng/ml, p < 0.05) levels in their luteal phase. Reduced LH might contribute to poor development of the ovarian corpus luteum, subsequently diminish P level. Decreased AMH level in three age groups: 21-30 years (1.4 ng/ml vs. 3.2 ng/ml, p < 0.01), 31-40 years (0.6 ng/ml vs. 2.1 ng/ml, p < 0.01), and >40 years (0.4 ng/ml vs. 1.7 ng/ml, p < 0.01) of Ladakhi women were recorded than their SL counterpart. Elevated oxytocin (83.5 ng/ml vs. 76.3 ng/ml, p < 0.05) and MIF levels (70.2 ng/ml vs. 49.7 ng/ml, p < 0.01) along with low P and AMH levels delineated the reason for recorded early menopause (43.9 years), shorter reproductive span (∼29 years), and history of miscarriage in HA dwellers compared to SL. Conclusion: Therefore, the findings insinuated that the response of the reproductive system to hypoxia in Ladakhi women differs from SL women, and the adaptive response in these women might be in favor of their reproductive health.

Alterations of estrous cycle, 3ß hydroxysteroid dehydrogenase activity and progesterone synthesis in female rats after exposure to hypobaric hypoxia.

The underlying mechanism regulating hypoxia induced alteration in female steroid hormones is first time explored in this study. To understand the mechanistic approach, female Sprague- Dawley rats were exposed to acute and chronic hypobaric hypoxia (282 mm-Hg, ~7620 m, 6 hours, 3 and 7 days). Estrous cycle, body weight, plasma progesterone and estradiol levels, morphology, histology and two key steroidogenic enzymes: 3ß hydroxysteroid dehydrogenase (HSD) and 17ß HSD activity of ovary and adrenal gland were studied. A persistent diestrous phase and a significant decrease in body weight were found in chronic hypoxia groups. Histological study suggested degenerative changes in ovarian corpus luteum of 7 days chronic hypobaric hypoxia (7CHH) group and a declined percentage of adrenocortical cells in 3 days chronic hypobaric hypoxia (3CHH) and 7CHH groups. Plasma estradiol level was unaltered, but progesterone level was decreased significantly in all hypoxic groups. Ovarian 3ß HSD activity was decreased significantly with increasing days of hypoxic treatment along with a significantly low adrenal 3ß HSD activity in 7CHH. In conclusion, hypobaric hypoxia causes a state of low circulatory progesterone level in females likely due to the degenerative changes in the female ovarian and adrenal tissues together with low steroidogenic 3ß HSD enzyme activity.

Impact of high altitude on key determinants of female reproductive health: a review.

Imperishable research work was done on females visiting high-altitude (HA) areas for recreational activities or job purposes as well as on female HA natives. Hypoxia at HA is an unavoidable condition that affects the determinants of female reproductive functions like, the age of menarche and menopause, whole reproductive span, hormone synthesis, and fertility. This review will emphasize whether HA hypoxia is a threat to women: residents or visitors by analyzing these proximate determinants. Delayed menarcheal and advanced menopausal age was found to shorten the reproductive span in some HA populations, whereas in some cases, menstrual cycle was also reported to be irregular. In addition, the completed fertility rate (CFR) was increased when people migrated to lower altitude. Altered stress hormones and reproductive hormones were observed in sea-level females exposed to HA. Oxidative stress (OS) at HA was also reviewed to explain the probable reasons for the observed changes in these determinants because disturbed redox homeostasis may be a connecting link, affecting the reproductive functions. In conclusion, HA hypoxia plays a crucial role on various determinants of female reproductive health and this review will be helpful for more precise study along with the probable underlying mechanisms responsible for the changes in female reproductive functions at HA.