In 2011, a report from a National Academy of Sciences' decadal survey emphasized the need to examine and understand the influences that sex and gender have on physiological and psychological or behavioral changes that occur during spaceflight.

In response, NASA and NSBRI assembled six workgroups to investigate and summarize the current body of published and unpublished human and animal spaceflight research data.

The groups focused on cardiovascular, immunological, sensorimotor, musculoskeletal, reproductive and behavioral implications on spaceflight adaptation for men and women. In June 2013, NASA and NSBRI hosted a virtual workshop to present the groups' findings.

The Journal of Women's Health published the manuscripts in the Nov. 2014 issue, available here.

As NASA sets its sights on longer-duration spaceflight deeper into the solar system, the health and safety considerations for its astronauts grow increasingly complex.

The agency, in partnership with the National Space Biomedical Research Institute (NSBRI), is researching risk-reducing countermeasures and developing technologies to advance human health and ensure operational performance in deep space. Together they are investigating personalized medicine for astronauts who may spend years living and working autonomously away from planet Earth.

A key consideration in personalized medicine is the crewmember's sex and gender. Although in recent years the definitions have become more nuanced in the clinical community, "sex" is defined here as the classification of male or female according to an individual's genetics and "gender" refers to a person's self-representation as male or female based upon social interactions.

We know that on Earth, major components of the human body are influenced by sex and gender factors. Taking gravity away from the equation imposes an entirely new element on our understanding of the health implications of sex and gender differences.

"Fortunately, we have the International Space Station," said Dr. Marshall Porterfield, Director of Space Life and Physical Sciences Research at NASA Headquarters.

"Station provides us with years of biological data on male and female astronauts, and many of them continue to participate in ground-based studies to evaluate the lasting effects of spaceflight."

Much of this data is available to the public through the Life Sciences Data Archive (LSDA) and the Lifetime Surveillance of Astronaut Health (LSAH), but there is an imbalance of data available for men and women, primarily due to fewer women who have flown in space.

The "Impact of Sex and Gender on Adaptation to Space" is a compendium of the work groups' six individual manuscripts, an executive summary, and a commentary. It is the most current, comprehensive report on sex and gender differences related to human physiology and psychology in spaceflight and on Earth.

The full compendium is available here.

Each workgroup included scientists and clinicians from academia, NASA or NSBRI, and other federal agencies and was co-chaired by one representative from NASA or NSBRI and one from the external scientific community.

The groups identified certain sex- and gender-related differences that impact the risks and the optimal medical care required by space-faring women and men. It represents innovative research in sex- and gender-based biology that impacts those individuals that are at the forefront of space exploration.

"Harnessing the power of 21st century personalized medicine, as practiced at leading medical schools and hospitals, will further mitigate the human health risks inherent to long duration deep space missions," said Jeffrey P. Sutton, M.D., Ph.D., NSBRI's President, CEO, and Institute Director.

The groups observed that the disparity of spaceflight data available for men and women who have flown in space - 477 men vs. 57 women as of June 2013 - makes it difficult to derive concrete conclusions based on sex and gender alone. In the latest crew selection, NASA selected eight astronauts, comprising four women and four men. This is a positive step toward increasing the participation of female astronauts in spaceflight and experimentation.

"This is the first major integrated examination of the issues of sex and gender in relationship to space exploration," said Dr. Mark Shelhamer Chief Scientist for NASA's Human Research Program at Johnson Space Center.

"There are, in many cases, sex-based differences in the response to the stressors of space flight." He believes that is important to recognize-not ignore-such differences, and to provide countermeasures that are appropriate for each subpopulation or even to each individual.

The Sex and Gender work groups released five recommendations:

+ Select more female astronauts for spaceflight missions.

+ Encourage and facilitate the participation of more female and male subjects in both ground and flight research studies.

+ Focus on the responses of individual astronauts to spaceflight and return to Earth.

+ Include sex and gender factors in the design of the experiments.

+ Incorporate sex and gender and other individual risk factors into NASA-funded research programs

A summary of the Sex and Gender work groups' major findings is listed below:

+ Orthostatic Intolerance, or the inability to stand without fainting for protracted periods, is more prevalent upon landing in female astronauts than in their male counterparts. One possible reason for this observed difference in orthostatic intolerance between the sexes is reduced leg vascular compliance, which was demonstrated in bed-rest studies - which is a ground analog for spaceflight.

+ Women have greater loss of blood plasma volume than men during spaceflight, and women's stress response characteristically includes a heart rate increase while men respond with an increase in vascular resistance. Still, these Earth observations require further study in space.

+ The VIIP syndrome (visual impairment / intracranial pressure) manifests with anatomical ocular changes, ranging from mild to clinically significant, with a range of corresponding changes in visual function. Currently 82% of male astronauts vs. 62% of women astronauts (who have flown in space) are affected. However, all clinically significant cases so far have occurred in male astronauts.

+ Changes in function and concentration of key constituents of the immune system related to spaceflight have been reported. However, differences between male and female immune responses have not been observed in space. On the ground, women mount a more potent immune response than men, which makes them more resistant to viral and bacterial infections; once infected, women mount an even more potent response. This response, however, makes women more susceptible to autoimmune diseases. It is not clear if these changes on the ground will occur during longer space missions, or missions that involve planetary exploration (exposure to gravity).

+ Radiation presents a major hazard for space travel. It has been reported that female subjects are more susceptible to radiation-induced cancer than their male counterparts; hence radiation permissible exposure levels are lower for women than men astronauts.

+ Upon transition to microgravity after arriving at the International Space Station (ISS), female astronauts reported a slightly higher incidence of space motion sickness (SMS) compared with men. Conversely, more men experience motion-sickness symptoms upon return to Earth. These data were however not statistically significant, due both to the relatively small sample sizes and small differences in the incidence of SMS reported by the men and women astronauts.

+ Hearing sensitivity, when measured at several frequencies, declines with age much more rapidly in male astronauts than it does in female astronauts. No evidence suggests that the sex-based hearing differences in the astronaut population are related to microgravity exposure.

+ The human musculoskeletal response to gravity unloading is highly variable among individuals and a sex-based difference was not observed.

+ Urinary tract infections in space are more common in women and have been successfully treated with antibiotics.

+ There is no evidence of sex differences in terms of behavioral or psychological responses to spaceflight. Analysis of ISS astronauts' neurobehavioral performance and sleep measures showed no sex or gender differences using the Psychomotor Vigilance Test (PVT) of alertness and Visual Analog Scales of workload, stress, and sleep quality. Since all all astronaut candidates undergo a robust process of psychological screening and selection, the likelihood of an adverse behavioral health condition or psychiatric disorder is greatly diminished.