Journal of Men’s Health and Gender. Vol 1. No.4 pp 341-344. Dec. 2004.
The case for an all-female crew to Mars
Former Assistant Clinical Professor of Medicine, Medical
A strong case can be made for an all-female crew, aged under 30 years, to Mars. The incidence of endothelial injuries on earth is six times higher in young men than in young women. On spaceflight, there is a far greater risk of endothelial injuries, with an accelerated aging process, complicating oxidative stress, and a Mg ion deficit with a self-sustaining inflammatory process. Pharmaceuticals in general are contraindicated because of malabsorption, and potential impairment in hepatic and renal perfusion. Also some pharmaceuticals deteriorate in space possibly associated with increased radiation. This prevents therapy for men in an attempt to compensate for their vascular disadvantages. Women have a considerable advantage because of endothelial protection, provided by estrogen, greater uptake of Mg in progressively diminishing storage sites in skeletal muscle and bone, and a physiological loss of iron, which is conducive to oxidative stress. Both estrogen and Mg are antioxidants and calcium blockers and compensate at least partly for diminished spaceflight vascular endothelial growth factor, thereby enhancing endothelial function, repair and angiogenesis. The only apparent disadvantage of an exclusively women crew for a Mars mission, may be the advisability of their avoiding space walks during menstruation, because of the greater risk at that time of decompression sickness. The optimal time would be during the follicular stage. © 2004 WPMH GmbH. Published by Elsevier Ireland Ltd.
Long before atherosclerosis develops, an inflammatory process adversely affects the endothelium . This process is more than six times more likely to occur in men than in women in the third and fourth decades of life . The endothelium throughout the cardiovascular system is far more vulnerable to injuries in space, not only in the heart but, for example, also in the liver and kidneys, which are required to metabolize and excrete pharmaceuticals . As in addition low gravity is invariably associated with malabsorption , pharmaceuticals appear to be contraindicated, except for symptomatic treatment and emergencies. In addition several pharmaceuticals have been shown to deteriorate in space possibly because of increased radiation (personal communication, L. Putcha). The marked difference between the sexes in vascular risk, without the opportunity to offset the male risk with drugs, leads to the logical conclusion that an all-female crew would be appropriate for a mission to Mars, which is expected to last about 2 years .
Repair of the endothelium is inadequate after the age of 30 years  therefore the crew should return from Mars before this time. Consequently loss of estrogen protection at menopause would not be an issue either. Furthermore the aging process is accelerated with spaceflight, probably because the hazards of age and spaceflight are associated, at least partly, with the vascular complications of magnesium (Mg) deficiencies [2,5].
The estrogen advantage
The cards are stacked against the man in space, starting with the vital role of estrogen for protecting the endothelium to fulfill nature's goal of preservation of the species by reproduction. Estrogen is an antioxidant and has been shown to increase endothelial-derived relaxing factor (nitric oxide) , which is reduced after spaceflight . Epinephrine levels are significantly lower in women , which reduces the likelihood of endothelial injury from catecholamine auto-oxidation, with in turn inactivation of nitric oxide . Increases in catecholamine concentrations trigger a vicious cycle of ischemia, which can produce an inflammatory response (Figure 1). In experimental animals estrogen also causes a dose-dependent decrease in heart rate , reducing the potential for ventricular fibrillation. During space walks heart rates can reach 170/ minute . On the Apollo 15 mission James Irwin had heart rates up to 167, and an arrhythmia associated with syncope shortly after leaving the lunar surface. He described classic symptoms of angina and severe dyspnea, but just during reentry at 7 Gs. Only 21 months later he suffered a myocardial infarction .
If a space walk is carried out within 6 hours of awakening the risk of endothelial injury is intensified . This circadian factor could be triggered partially by higher morning epinephrine levels, which importantly, for space, are not affected by posture . Here again, women would have less risk of endothelial injuries because their epinephrine levels are significantly lower than those of men, as noted above . With lower epinephrine levels, the heart rate on space walks would be predictably lower in women, with less risk of a serious arrhythmia as well.
Estrogen also has a favorable effect on endothelial function and repair and has been shown to increase angiogenesis . These functions are particularly useful in spaceflight to assist in compensating the reduction that occurs in platelets. Platelets are the primary source of vascular endothelial growth factor (VEGF) [15,16], which is required for endothelial function and repair, as well as angiogenesis.
Estrogen is also a calcium (Ca) blocker , which would reduce the potential for Ca overload of the mitochondria, shown in experimental animals after spaceflight. These animals also had endothelial injuries . Furthermore elevations of carbon dioxide on spaceflight have been postulated to be conducive to an intracellular shift of Ca , which may be less likely in female astronauts . ( See Figure 1)
Lessons from Apollo
A few years ago, I described, what I called " The Apollo 15 Space Syndrome" , characterized by severe pain and edema of the finger tips, which were experienced by Irwin and Scott on the lunar surface (all the lunar missions had men only crews). I postulate that this syndrome is due to significant vasospasm of both the arterioles and venous system of the fingers, with fluid trapped distally, and furthermore that these adverse effects could serve as a warning of possible silent ischemia of the coronaries, complicating vasospasm. Considering estrogen reduces vascular smooth muscle tone , I postulate that women are far less likely to experience this syndrome .
The magnesium factor
Men have the wrong genes for space because the male gene ensures higher catecholamine levels  for "fight-flight", which was vitally important for prehistoric man. One mechanism, conducive to lower Mg ion levels in men, stems from a greater removal of Mg ions from the circulation by chelation, secondary to higher catecholamine-induced free fatty acids. In addition to an ischemic mechanism, formation of higher concentrations of free fatty acids in men would increase the potential for a direct myocardial injury . If in an attempt to reduce spaceflight osteoporosis excess Ca is taken, resulting in an intake of Ca to Mg in a ratio higher than 2:1 still higher levels of catecholamines will be released . The result will be that two of the spaceflight cycles will become even more vicious! (Fig. 1).
On the other hand, estrogen's enhancement of the utilization and uptake of Mg in skeletal muscle and bone provides an important advantage for women in space, though insufficiently appreciated because of the insensitivity of normal serum Mg levels. About 60% of Mg is stored in bone. The remainder is stored in skeletal muscle and soft tissues . All the various spaceflight-specific countermeasures, developed over the past four decades, have failed to reduce appreciably the loss of this bone / skeletal muscle reservoir. About 1% of bone is lost per month in space. Magnesium not only reduces the potential for osteoporosis , but is required for the maintenance of over 300 separate enzymes . It shares several functions already described for estrogen. Magnesium is both an antioxidant  and Ca blocker , and shares the vital roles of regulating endothelial function and repair and angiogenesis with VEGF (reduced in space) and estrogen . In addition, a Mg ion deficit, can lead to adverse effects on the endothelium, characterized by self-sustaining inflammation  and triggered by elevations of catecholamines, cytokines, aldosterone and angiotensin, with angiotensin intensified by invariable dehydration. All of these effects have been shown in humans in space [5,8,21]. Insulin resistance, which can be precipitated by a Mg ion deficit, has also been shown in space and this also is conducive to oxidative stress and endothelial injury . Women on marginal Mg intakes, which is likely to occur on spaceflight due to invariable malabsorption , are less likely to develop a Mg ion deficit than men are .
Too much iron in men
Another advantage of women is their loss of iron through menstruation. In space with a Mg ion and protein deficit as well as insulin resistance, there would be a potential reduction in the protein transferrin which binds iron (Fig. 1). Increased free iron can be "extremely toxic" because it is conducive to high oxidative stress .
It is unfortunate that many women on spaceflight use oral contraceptives to regulate their periods and reduce blood flow, which partially offsets their iron loss advantage (22). Men on the other hand have no physiological way of losing iron. Furthermore oral contraceptives are conducive to increased clotting, which would compound the potential for clot formation from endothelial injuries, catecholamine elevations and Mg ion reductions with several vicious cycles [2,5] (Fig. 1).
Space walks and the menstrual cycle
The endothelium is vulnerable, particularly during space walks, to potential dysfunction/injury, which complicates decompression sickness, and because of the 100% oxygen which is inhaled for over 2 hours before a space walk. Oxygen is inhaled to reduce the risk to the endothelium from nitrogen bubbles (decompression sickness) and is required during a space walk up to 8 hours in duration . This hyperoxia can inactivate nitric oxide  and reduce VEGF as well as the expression of VEGF . For this reason and because of the increased potential for decompression sickness with injury to the endothelium during menstrual periods, space walks should be avoided at the time of menstruation. The optimal time for space walking is during the follicular stage, when the risk is reduced with Mg, estrogen and estrogen receptor levels higher, and endothelial function is improved . It appears that this scheduling preference may be the only medical advantage of men on space missions.
Women also have the advantage in space of reduced mass, requiring less consumable demand and waste production. On a space mission, anticipated to last about 2 years, these characteristics are particularly advantageous.
More information about this fascinating subject can be found at www.femsinspace.com.
"Its amazing what you can learn from a men's health and gender journal .Women make better astronauts than men :physically they are more suited to space flight .As pharmaceuticals are contraindicated in space the possibility of neutralising the female advantage is precluded ------ In a nutshell, it questions gender-specific fitness for certain occupations and also begs for further research into sex-specific medical attributes ."
Siegfried Meryn, MD, Editor -in-chief, Journal Men's Health and Gender. vol.1 No.4 pp.285-287,Dec. 2004.
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