The inability to draw statistical comparisons based on gender differences is linked to the small number of female astronauts, resulting in an insufficient study sample. In addition, individual differences in physiological responses within genders are usually as large as, or larger than, differences between genders, so individual characteristics usually outweigh gender differences per se.

Despite these obstacles, a minireview in the November edition of the Journal of Applied Physiology, a publication of the American Physiological Society (APS), offers a summary of gender-specific physiological changes and health issues in astronauts for future consideration and in light of the expectation that the number of female astronauts will grow.

The review is part of the APS's fall focus on gender differences in physiology. It provides an overview of known and potential gender differences in physiological responses to spaceflight and covers cardiovascular and exercise physiology, barophysiology and decompression sickness, renal stone risk, immunology, neurovestibular and sensorimotor function, nutrition, pharmacotherapeutics, and reproduction.

Highlights of the review included:

Pharmacotherapeutics

Gender-related differences are known to exist with respect to clinical efficacy and adverse effects of drug treatment. There is a general consensus among clinical pharmacologists that pharmacokinetics and pharmacodynamics in women are different from those in men. Gender differences in gastrointestinal physiology and hepatic metabolism may contribute to differences in drug dynamics. In addition, hormonal changes during the menstrual cycle, renal blood flow, and body composition also play roles in gender-specific drug disposition.

Gastrointestinal Physiology and Hepatic Metabolism

Women may have adverse effects on their drug absorption, biovariability, metabolism, and elimination due to gender differences in gastrointestinal physiology and hepatic metabolizing enzyme systems. They also have altered bile composition, slower intestinal transit time, and higher gastric pH than men. During the first few days of spaceflight, there is a high incidence of space motion sickness (SMS) accompanied by decreased gastrointestinal motility. The combination of initial slower intestinal transit time and decreased gastrointestinal motility associated with SMS may adversely affect absorption and bioavailability of orally ingested medications more in female than in male astronauts. Clinically significant gender differences have been reported for drug elimination processes; these were predominantly linked to the gender-specific expression of metabolic enzyme systems. Differences between men and women in hepatic phase I and phase II metabolism have an important influence on drug metabolism. Men have higher levels of certain metabolizing enzyme isoforms, whereas women have higher activity levels of different isoforms. These differences in drug metabolism may partially account for the higher incidence of adverse reactions to drugs in women than in men.

Hormonal Changes

Menstrual cycle hormonal changes can also influence drug absorption, distribution, metabolism, and elimination, and oral contraceptive use can interfere with the metabolism of many drugs. Due to the absolute preclusion of pregnancy in space, many female astronauts choose oral contraceptives during the training period, and most continue to use them while on orbit. Changes in the renal, cardiovascular, hematological, and immune systems during menstruation are well known, and these physiological changes could influence the pharmacokinetics and pharmacodynamics of drugs by altering such variables as protein binding and volume of distribution of drugs, which could significantly worsen disease severity.

Normal Menstrual Function

Because space shuttle flights are considerably shorter than the average menstrual cycle length, no on-orbit studies have been done to determine the impact of microgravity on normal hypothalamic/pituitary/ovarian axis function. The primary concern is that anovulation might occur, resulting in continuous estrogen exposure, endometrial hyperplasia, and possibly menorrhagia. Second, there is some concern that hypothalamic amenorrhea and reduced estrogen levels could occur. The reason for concern is that the exercise necessary for long-term cardiovascular and musculoskeletal fitness may be strenuous enough to cause hypothalamic- induced hypogonadism with reduced serum estrogen levels. The combined effect of hypoestrogenemia and spaceflight-related calcium loss could lead to increased osteoporosis risk.

Menstrual Efflux and Retrograde Menstruation Many women normally experience some retrograde intra-abdominal bleeding during menses. Because of the effects of gravity, the blood products and cellular debris usually stay confined to the pelvis. The development of endometriosis is multifaceted, but exposure of the pelvic peritoneum to menstrual blood products is thought to be the primary cause of its development. Endometriosis is also primarily a pelvic problem in part because gravity keeps the menstrual products confined to the pelvis.

Although medical debriefing data from shuttle flights have not supported concern that retrograde menstruation increases during spaceflight, the role of gravity in menstruation should be investigated to determine whether retrograde menstruation is increased and how peritoneal fluid is distributed. In addition, radiation exposure at varying doses has been associated with the development of endometriosis in certain primate species.

Radiation, Fertility

Radiation concerns for women and men are generally similar except for exposure of the gonads and breast and thyroid tissue. Although the radiation exposure levels found in long-duration spaceflight may present an infertility problem for men, this is not likely for the more radiation-resistant ovary. However, the effect of space-based radiation on the chromosomes of oocytes is of considerable importance to women who may desire future pregnancies.

Compared with women, men are at considerably increased short-term risk from damage to gametes. However, the effect of neutrons, high-energy particles, and other radiation from space needs to be assessed for both men and women on prolonged missions so that they can make informed decisions regarding cryopreservation of gametes before flight.

The participation of women in spaceflight piques the interest of the public in issues relating to pregnancy and fertility in space. However, the radiation levels associated with spaceflight in low Earth orbit or deep space preclude pregnancies at this time. The National Council on Radiation Protection and Measurements guidelines limit radiation exposure to 500 mrem for an entire pregnancy and to only 50 mrem per month. The International Commission on Radiological Protection guidelines are more restrictive. On the International Space Station, radiation exposure to a pregnancy may approach 35,000 mrem or more. Radiation exposure on the International Space Station varies with altitude, solar cycle, and location of the astronaut in the space station. Thus, during a nine month pregnancy, exposure could range from 10,500 to 36,000 mrem, depending on the altitude of the station and the solar cycle.

Cardiovascular Physiology

Generally, women have lower blood pressure and peripheral vascular resistance and higher heart rates than men. In addition, women respond to cardiovascular stress with greater heart rate increases, whereas men respond primarily with greater increases in vascular resistance. In one study designed to examine postflight orthostatic intolerance, the presyncopal astronauts (five women and three men) were found to have greater increases in heart rate, greater decreases in blood pressure, and less of an increase in peripheral resistance in response to the postflight stand test than their nonpresyncopal counterparts (two women and 19 men). It was suggested that indirect vasodilatory effects of estrogen in premenopausal women may contribute to smaller vasoconstrictive responses in women compared with men during orthostatic stress.

Ventricular Dysrhythmias

New data suggest that cardiac dysrhythmias may be of greater concern during long-duration than short-duration spaceflight. In the general population, men in this age group have a greater risk of ventricular dysrhythmias than women. It would, therefore, be expected that in the astronaut population this would hold true as well.

Exercise Physiology

At the present time, 22 percent of the active astronaut corps are women (35 of 158). The average female astronaut is 42 years old (43 years for men) and weighs 60.7 kg (81.2 kg for men). In general, the average woman is 10 cm shorter and 13 kg lighter and has 11 percent more body fat, 8 percent less muscle mass, 10-14 percent less hemoglobin mass, and a lower level of aerobic fitness than her male counterpart. These gender differences can be expected to influence exercise capacity and thus the ability to perform specific tasks during spaceflight.

Aerobic Fitness

The average aerobic fitness, expressed as the maximal oxygen uptake of adult women is 2.0 l/min, compared with 3.5 l/min for men. When adjusted for differences in body weight, the average maximal uptake for women is 40 vs. 50 ml/kg for men. (These differences can be reduced still further.) Thus, for any task requiring a given absolute oxygen uptake, the average woman is working at a higher percentage of her exercise capacity than the average man.

This would result in a higher heart rate, higher body temperature, greater stress, and a quicker onset of fatigue during the exercise. These more severe exercise responses may result in a greater number of injuries and less tolerance for a stressful environment. For example, in a study of 124 men and 186 women during basic combat training, the women had a 51 percent injury rate compared with 27 percent for the men.

The average woman is less active and less fit than the average man. Therefore, when exercise data are normalized for fitness, the gender differences often are greatly reduced. If allowed to work at a similar percentage of their maximal exercise capacity, men and women would have similar cardiovascular and thermoregulatory responses. However, men tend to be faster than women during aerobic events due to their greater muscle strength and the mechanical advantage of their longer arms and legs. Women, on the other hand, tend to have a greater endurance capacity due to a greater reliance on fat metabolism during exercise; thus a glycogen-sparing effect might delay fatigue during long-duration events.

At this time, there is not sufficient data to compare the degree of aerobic deconditioning after spaceflight between men and women. However, in response to bed rest, the relative changes in aerobic capacity are similar between men and women despite the marked differences in absolute values.

Strength

There are obvious strength differences between the average man and the average woman. Body strength of the adult woman is about two- thirds that of the adult man. Upper body strength of the woman is 50 percent that of the man, whereas lower-body strength is 70 percent. Few data exist concerning strength changes in women after spaceflight or bed rest. Regional decreases in muscle volume were similar in two men and two women after eight days of spaceflight.

Some reports, however, indicate that women have a greater percentage of slow-twitch muscle fibers than men. Slow-twitch muscle fibers appear to be more affected by spaceflight than the fast-twitch fibers. If this is the case, women may be more susceptible to changes in muscle mass and endurance. This hypothesis has yet to be tested. In response to strength training, women and men have a similar proportional increase in lean body mass and strength, yet the total muscle girth of the women is less. These consistent differences in muscle mass of men and women are believed to be attributable to the anabolic effect of the 20- to 30-fold greater concentration of testosterone in men.

This summary is derived from a special task-force report developed by Deborah L. Harm, Janice V. Meck, Michael R. Powell, Lakshmi Putcha, Clarence P. Sams, Suzanne M. Schneider, Linda C. Shackelford, and Scott M. Smith, of the Human Adaptation and Countermeasures Office, NASA Johnson Space Center, Houston, Tx.; Richard T. Jennings, Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Tx., and Peggy A. Whitson of the Astronaut Office, NASA Johnson Space Center, Houston, Tx.

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