High serum testosterone levels are associated with excessive erythrocytosis of chronic mountain sickness in men

Abstract

Chronic mountain sickness (CMS) is characterized by excessive erythrocytosis (EE) secondary to hypoventilation. Erythropoietin (Epo) and testosterone regulate erythrocyte production. Low thyroid hormone levels are also associated to hypoventilation. Hence, these hormones can play a role in etiopathogeny of EE. The purpose of this study was to elucidate the effect of sexual and thyroid hormones and Epo in residents from Lima (150 m) and Cerro de Pasco (4,340 m), Peru, and the response to human chorionic gonadotrophin stimulation (hCG). Three groups, one at low altitude and two at high altitude [1 with hemoglobin values >16-21 g/dl and the second with Hb >or=21 g/dl (EE)], were studied. hCG was administered intramuscularly in a single dose (1,000 IU), and blood samples were obtained at 0, 6, 12, 24, 48, and 72 h after injection. High-altitude natives present similar levels of gonadotropins and thyroid hormones but lower dehydroepiandrosterone sulphate (DHEAS) levels (P < 0.01) and greater Epo (P < 0.01), 17alpha-hydroxyprogesterone (P < 0.01), and testosterone levels (P < 0.01) than those at 150 m. Serum testosterone levels (524.13 +/- 55.91 microg/dl vs. 328.14 +/- 53.23 ng/dl, means +/- SE; P < 0.05) and testosterone/DHEAS ratios are higher (7.98 +/- 1.1 vs. 3.65 +/- 1.1; P < 0.01) and DHEAS levels lower in the EE group (83.85 +/- 14.60 microg/dl vs. 148.95 +/- 19.11 ug/dl; P < 0.05), whereas Epo was not further affected. Testosterone levels were highest and DHEAS levels lowest in the EE group at all times after hCG stimulation. In conclusion, high androgen activity could be involved in the etiopathogeny of CMS. This evidence provides an opportunity to develop new therapeutic strategies.

Fig. 1.

Serum testosterone/dehydroepiandrosterone sulfate (T/DHEAS) ratio in men from Lima and Cerro de Pasco, Peru, with Hb values >16–21 g/dl (CP-1) and >21 g/dl (CP-2). Data are means ± SE. *P < 0.01 with respect to Lima; **P < 0.05 with respect to values in CP-2 (men from Cerro de Pasco with Hb values >16–21 g/dl).

Fig. 2.

Response of men at low altitude (150 m) and at high altitude (4,340 m) to 1,000 IU of a single intramuscular injection of human chronic gonadotropin. Men from high altitudes have been grouped according to Hb levels. Men from low altitudes have been considered as control, and men from high altitudes have been grouped according to Hb levels in Hb >16–21 g/dl and Hb >21 g/dl. A: serum response of 17α-hydroxyprogesterone (17-OHP) levels. B: response of serum DHEAS. C: response of serum testosterone. D: response of serum estradiol levels. For analysis, estradiol levels and DHEAS levels were logarithmically transformed. Data are means ± SE.