Each year, millions of people living at low altitude (< 1,000 m) travel to high altitude (≥ 2,500 m) for work, tourism, or sports activities. These individuals are exposed to hypobaric hypoxia, which can trigger acute mountain sickness (AMS)-the most common form of altitude-related illness. Therefore, understanding the physiological responses to hypoxia that allow acclimatization, as well as the pathophysiology of acute mountain sickness, is of primary importance.

The hematological response to high-altitude exposure initially includes a reduction in plasma volume (PV), leading to an early increase in hemoglobin concentration within the first 24 hours. In contrast, an increase in hemoglobin mass requires several weeks at high altitude. Recent well-controlled physiological studies conducted in hypobaric chambers have demonstrated that this hypoxia-induced PV contraction results from fluid redistribution from the intravascular to the extravascular compartment, rather than from water loss due to increased diuresis.

Prophylaxis of AMS is primarily based on the administration of 250 mg/day of acetazolamide (ACZ), a carbonic anhydrase inhibitor with a mild diuretic effect. Acetazolamide induces metabolic acidosis, which stimulates ventilation and thereby improves oxygenation. The effect of prophylactic ACZ use during high-altitude exposure on PV in lowlanders remains unknown: it is unclear whether ACZ leads to a greater reduction in PV due to its diuretic effect, or to a smaller hypoxia-induced PV contraction as a result of improved oxygenation induced by increased ventilation.

Not provided

Inclusion Criteria:

• Healthy, non-smoking men and women, age 18-44 years, without any disease and need of regular medication (including oral contraceptives).
• BMI >18 kg/m2 and <30 kg/m2.
• Born, raised and currently living at altitudes <1000 m.
• Written informed consent.
• Premenopausal women with an eumenorrheic cycle.

Exclusion Criteria:

• Other types of contraceptvies (contraceptives (hormonal intrauterine device, vaginal ring, subcutaneous injections or implants, among others).
• Pregnancy or nursing
• Anaemic (haemoglobin concentration <10g/dl).
• Any altitude trip <4 weks before the study.
• Allergy to acetazolamide and other sulfonamides.

Only IPD used in the results publication