Millions of people travel to high altitude for work or leisure activities and are exposed to reduced inspiratory oxygen partial pressure and hypoxemia that may lead to altitude illness, among which the most common form is acute mountain sickness (AMS). The main AMS symptoms are headache, malaise, weakness, and fatigue. Prospective studies have shown that 20-60% of newcomers at 2500-4000m develop AMS requiring them to take medications, while, at very high altitudes, AMS may progress to high altitude cerebral oedema. Whether women are more susceptible to AMS remains insufficiently understood since no prospective study controlled for sex hormones, use of hormone contraception or assessed menstrual cycle phase (MCP) at altitude. Therefore, women remain underrepresented and poorly characterized in high altitude studies. In addition, the efficacy and safety of 250 mg/day acetazolamide, the standard recommendation for AMS prevention, has never been compared between sexes, although, women have presumably higher acetazolamide plasma concentration due to lower blood volume. Given the known dose-dependent preventive but also side effects of acetazolamide and equal proportion of women and men among mountain travellers, there is an urgent need to conclusively quantify the efficacy and safety of pre-ventive acetazolamide therapy against AMS in women compared to men.

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