Review

International Journal of Impotence Research (2005) 17, S64–S67. doi:10.1038/sj.ijir.3901431

Genitourinary issues during spaceflight: a review

J A Jones1, R Jennings2, R Pietryzk3, N Ciftcioglu4 and P Stepaniak1

  1. 1NASA/Johnson Space Center, Houston, Texas, USA
  2. 2University of Texas Medical Branch, Galveston, Texas, USA
  3. 3M.S. Enterprise Advisory Services, Inc., Houston, Texas, USA
  4. 4Nanobac Life Sciences, Inc., Tampa, Florida, USA

Correspondence: JA Jones, MD, NASA/Johnson Space Center, Houston, TX, USA.

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Abstract

The genitourinary (GU) system is not uncommonly affected during previous spaceflights. GU issues that have been observed during spaceflight include urinary calculi, infections, retention, waste management, and reproductive. In-flight countermeasures for each of these issues are being developed to reduce the likelihood of adverse sequelae, due to GU issues during exploration-class spaceflight, to begin in 2018 with flights back to the Moon and on to Mars, according to the February 2004 Presendent's Vision for US Space Exploration. With implementation of a robust countermeasures program, GU issues should not have a significant threat for mission impact during future spaceflights.

Keywords:

spaceflight, genitourinary, reproduction, calculi, urinary retention

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Introduction

There are many physiological effects and medical issues that impact spaceflight missions. The genitourinary (GU) system is not uncommonly affected during spaceflight. In total, 10% of astronauts participating in Shuttle flights between 1981 and 1998 (89 missions), which included 508 crew (439 men, 69 woman) over 4443 flight days, reported GU symptoms during flight.

Obviously, issues in the GU system can adversely affect the sexual health of the astronaut and therefore have relevance to the focus of this special issue.

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Issues of GU health

GU issues during spaceflight can be categorized as follows: upper tract, lower tract, waste management, and reproductive health.

Upper tract

The two previously observed conditions affecting the upper tracts during spaceflight are calculi and related obstruction.

Urinary calculi have been observed on one occasion in-flight and 14 occasions postflight. The one in-flight episode occurred in a Russian cosmonaut during a long-duration mission on the Salyut, which nearly resulted in the crewmember being medically evacuated due to inability to control his pain resulting from transient obstruction of the upper collecting system from a stone lodged in the distal ureter. In total, 11 US crewmembers have had 14 urinary calculi following their spaceflights, all after missions less than 2 weeks in duration.1, 2

Space travelers are at risk of urinary calculi due to the mobilization of calcium from the bone when exposed to prolonged microgravity. Due to tight regulation of calcium levels in the blood, the mobilized bone mineral during periods of un-weighting is excreted by the kidney, resulting in increased concentration of calcium in the urine, and thereby increased solubility product of calcium salts like calcium oxalate. Long-duration spaceflight in LEO (Low Earth Orbit) poses a greater risk for an in-flight stone.

Exploration Missions envisioned for the Moon and Mars will vary in mission length from a few weeks to perhaps 2–3 y. During these missions, the transit phase from LEO to the planetary surface, traversing interplanetary space, will likely expose the crewmember to microgravity for extended periods, ranging from 4 to 6 days between the Earth and Moon to 4–9 months, depending on the propulsion system and vehicle trajectory. After reaching the planetary surface, the crewmember's musculoskeletal system will be under the influence of reduced or partial gravity. In the case of the Moon, the gravity is approximately 1/6 of that of the Earth, while on Mars approximately 1/3 (0.38 g). It is not currently known how well ambulation in partial gravity will maintain the musculoskeletal system on its own; hence, the need for both transit phase and planetary surface operational countermeasures. Also for Mars missions, a contingency management strategy has been developed at NASA/JSC for endoscopic management of a ureteral calculus during spaceflight under ultrasound guidance.3

A question currently under investigation at the NASA/JSC by N Ciftcioglu and co-workers is whether nanobacteria, which may have been found in 1996 inside a Martian meteorite, can play a role in the pathogenesis of human calcific diseases such as urinary and prostatic calculi. Nanobacteria or 'nanoparticles' have been found to reproduce more vigorously in bioreactor microgravity simulators, and thus may pose a greater hazard in microgravity than on the ground, if their human pathogenecity is proven.4, 5

Another potential countermeasure, which that has been evaluated in ambulatory bedrest subjects, and extensively in clinical use for osteoporosis patients is the bisphosphonate Aledronate.6 Bisphosphonates act by inhibiting the action of osteoclasts in mobilizing calcium from bone hydroxyapatite. Bisphosphonates, like AG, have the potential to be protective of both the musculoskeletal and GU systems by reducing the loss of bone mineral calcium. An ISS spaceflight study of the bisphosphonates Aledronate and Zoledronic acid was recently approved by nonadvocate review team reporting to NASA headquarters (Supplemental Medical Objective Leblanc, JA Jones et al). It is expected that bisphosphonates will be used synergistically with resistive exercise and perhaps AG if it is operationally employed for exploration missions.

The last countermeasure that may be effective for reducing the risk of urinary calculi in flight is currently under flight study on the Shuttle and ISS, is potassium citrate, in the form of Urocit-K™ (Mission Pharmacal).7 A mid-study interim analysis is being conducted by the investigators at the time of this manuscript preparation.

Lower tract

Urinary tract infections (UTIs)
 

UTIs have occurred on multiple occasions during spaceflight with multiple likely causative mechanisms. Certainly, individual physical and mental stress, dehydration and hygiene likely played a role during the UTI acquired during Apollo 13. Other hygiene issues such as collection devices and factors such as delayed access to voiding and urinary stasis are thought to also play a role in the UTI cases. One case of prostatitis on the Salyut resulted in sepsis and subsequently a medical evacuation of the patient. Diagnosis of UTI is aided on-orbit by urine chemistry analysis strips (US) and an onboard urine analyzer (Russian). The combination of symptoms plus positive findings of leukocyte esterase or nitrites on the urine strip make a diagnosis of UTI very likely. UTIs are easily treated with oral antibiotics flown in the ambulatory medical kit.

Countermeasures for UTIs include good perineal hygiene, clean urine collection system interface, adequate fluid hydration, and nominal time to void after urge to void sensed (minimal delay in voiding). Occasionally, if the GU system is compromised by an indwelling catheter or intermittent catheterization (ICC-Intermittent Clean Catheterization), then prophylactic antisepsis or antibiotics can be used, for example, qHS nitrofurantoin while receiving ICC.8

Retention
 

In the history of short-duration flight on the Space Shuttle, there have been four cases of urinary retention requiring bladder catheterization. The cause of these cases is again multifactorial, and includes pharmacologic side effects (anticholinergics such as antiemetics used to treat space motion sickness), delay in voiding (due to schedule and waste control system availability), impaired sensorium, and possibly even microgravity itself (psychological and lack of gravity vector differences in voiding technique).9 The added risks associated with long-duration flight for urinary retention are two-fold: (1) possibility of outlet obstruction from prostate or urethral infection/inflammation, and (2) progression or recurrence of a pre-existing condition, for example, a urethral stricture managed by dilatation, may have time to recur during a long-duration flight. Screening should be performed for preflight conditions with potential for recurrence/progression and most likely excluded from long duration flight eligibility.

Countermeasures for urinary retention include avoiding delays in voiding, selection criteria for predisposing conditions as mentioned above, plus close monitoring of crew receiving anticholinergic medications, to include ICC if required to drain urine from bladder before overdistension injury can occur.

Urinary waste

Urine is disposed of on-orbit via waste collection systems (WCS). Both the US and Russian toilets take advantage of negative pressure induced from fluid separation systems to effectively 'acquire' liquid waste from the crewmember (mild suction like a weak shop vacuum cleaner). In both systems, a funnel attached to a length of flexible tubing serves as the point of interface between the WCS and the crewmember.

Reproductive health

The known postflight effects of short duration (mean 9 day spaceflights) in LEO on all US astronauts, male and female, are as follows:

  • Have had normal conception in both genders within 1 week after space flight,
  • 56 post-flight pregnancies,
  • 11 pregnancies within 1 y of space mission,
  • 17 postflight births in female astronauts,
  • 9 miscarriages; 2 stillbirths in all astronaut couples (4/11 in female astronauts),
  • 2 with chronic genetic diseases,
  • 43 healthy children.

These data are summarized with the knowledge that not all potential conception events and spontaneous abortions are captured. This rate of loss compares reasonably to the US miscarriage rate over the last several decades of: 10–20%—women age 20s, 25%—age 30s, 33%—age 40, 50%—>45. Considering the usual delay in pregnancy and average age of conception and delivery in the US female astronaut corps, it does not appear that short-duration spaceflight has an adverse affect on the ability of astronauts to conceive and bear healthy children to term. However, age, due to the chosen delay in conception resulting in increased age, and perhaps other factors, for example occupational stress, there may be an issue with fertility in female crewmembers.

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Assisted reproductive technology

There are several factors that support the need for a policy at NASA regarding Assisted Reproduction Technology (ART) for astronauts. The primary concerns are age-related fertility decline that occurs as female astronauts delay pregnancies for training/spaceflight and the effect of radiation-induced gamete damage for individuals of both sexes. The per-cycle fecundability for natural and assisted cycles begins to decrease considerably in women at age 32. This is not a particular problem for men. Since the average age of an incoming female astronaut is 32, and many wish to delay pregnancy until after their first spaceflight, most are approaching 40 by the time an appropriate window opens for them to conceive. Pregnant astronauts are not allowed to train in the NBL, vacuum chamber, KC-135 zero G aircraft, or fly in T-38s during their pregnancies. Pregnancy is prohibited for spaceflight. Some international travel is also restricted. In order to complete necessary training and compete for flight assignment with their selection classes, they female astronauts often usually avoid pregnancy early in their astronaut careers.

Based on the analysis of the current astronaut pool, about 80% come to NASA without previously having delivered children. The average maternal age in successful pregnancies occurring after spaceflight is 41–42 y. By this time, the chance for genetic defects and miscarriage has increased considerably, as stated above, and fertility has declined. In fact, many astronauts have been unsuccessful in conceiving at this stage of their life even though they have used all the technology available. In addition, the known miscarriage rate in female astronauts after spaceflight exceeds 40%. While this high rate is most likely due to age, it reduces the chance of successfully completing a pregnancy. Figure 1 is compiled from SART data and was provided by Dr Bill Gibbons from the Jones Institute at the Eastern Virginia Medical School. This was the first institution in the US to perform successful IVF. It clearly shows the reduction in successful pregnancies with IVF based on age, with the decrease beginning at 32 y of age (exact average age of a new astronaut). Spontaneous pregnancies undergo a similar age-based decrease. We do not know if spaceflight per se affects fertility (Figure 1).

Figure 1.
Figure 1 - Unfortunately we are unable to provide accessible alternative text for this. If you require assistance to access this image, please contact help@nature.com or the author

% of successful pregnancies vs age in women using own vs donor eggs.

Full figure and legend (40K)

The effects of long-duration flight and especially exploration class spaceflight on the reproductive capacity of humans are not currently known.

Since the radiation environment found on Earth does not contain the highly ionized heavy particles found in space that penetrate tissue deeply and may cause important nuclear damage, it is difficult to provide guidance regarding risks to male or female gametes in spaceflight. On-going studies at the Brookhaven National Laboratories accelerator may help reduce the risk uncertainty. One solution to this problem is to provide a program for individuals of both sexes to store gametes on Earth for future use. This is especially true for planned exploratory missions to Mars missions, where there is still sizeable uncertainty about the biological effects of high-energy particle radiation (HZE) on the reproductive tissues. For women, banking eliminates the potential problem of damage to gametes due to galactic cosmic radiation, solar particle events, and trapped radiation. It also augments fertility since the pregnancy and miscarriage rates for embryo transfer are dependent on the age of the gametes at the time of collection. Cryopreservation of embryos is preferred because the technology to store oocytes is not yet reliable. Eventually, other options may include the cryopreservation of ovarian tissue. For male crewmembers, sperm cryopreservation technology is well established and easily implemented with long-duration storage capability.

There is no currently NASA-sponsored program for assisted reproductive technology for astronauts of either gender. The female astronauts who have used ART for fertility reasons (approximately 10 individuals or about 25% of all women astronauts) have done so at their own expense. NASA is considering the budgetary impact of supporting ART services for its crewmembers. The delay in obtaining pregnancies while younger is due in large part to the unpredictable flight schedule and sacrifices made for the program during training. Other than the problem with radiation exposure to gametes, this situation is unique for the female astronauts because the male astronaut's ability to have a family is not tied to the flight or training schedule.

In-flight reproductive activity is possible from studies on multiple species that have flown in space on several prior short duration flights, both in the Russian (Bion) and US (Shuttle) programs. There have been both normal and abnormal reproduction patterns in animals observed during spaceflight. Animals studied include those pregnant prior to launch and those pregnant immediately after launch. Several species were observed to have diminished mating rates and relatively higher number of fetal deaths compared to terrestrial controls, but only in specific species, while other species did not seem to be adversely affected during spaceflight.

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Conclusions

GU medical events have shown to be an issue for both short duration and long duration spaceflight, and are anticipated to also be a potential issue for future exploration missions as well. This is based on actual historical pre-, in- and postflight medical events, as well as assessment of what future flight challenges lay ahead. However, a well-designed strategy of selection, monitoring, and preventive medicine with effective countermeasures, along with an easily implementable program of early imaging diagnosis and minimally invasive contingency intervention, should prevent GU issues from having any significant mission impact for solar system exploration.

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References

  1. Pietrzyk RA, Jones JA, Sams CF, Whitson PA. Characteristics of renal stone formation among US astronauts. Aviation Space Environ Med 2005 (submitted).
  2. Pietryzk R, Whitson P, Jones J, Sams C. Overview of renal stones and space flight. Bulletin of the 14th International Academy of Astronautics—Humans in Space Symposium: Living in Space: Scientific, Medical, and Cultural Implications, Banff, Alberta, Canada, May 22 2003.
  3. Jones JA, Johnston S, Campbell M, Billica R. Endoscopic surgery and telemedicine in microgravity, developing contingency procedures for exploratory class space flight. Urology 1999; 53: 892–897. | Article | PubMed | ISI | ChemPort |
  4. Jones JA et al. Association of calcifying nanoparticles within serum and prostates of patients with prostatic inflammation and hyperplasia: a preliminary analysis. Society of Inflammation and Infection in Urology Session at the American Urological Assn. Annual Meeting, San Antonio, TX 2005 May.
  5. Kajander OE, Ciftcioglu N, Katya A, Garcia-Cuerpo E. Characteristics of nanobacteria and their possible role in stone formation. Urol Res 2003; 31: 47–54. | PubMed | ISI |
  6. Young LR. Artificial Gravity' Encyclopedia of Space Science and Technology Vol 1. John Wiley and Sons, Inc.: New York, 2003 pp 138–151.
  7. LeBlanc AD et al. Alendronate as an effective countermeasure to disuse induced bone loss. J Musculoskel Neuron Interact 2002; 2: 335–343. | ChemPort |
  8. Pietrzyk RA et al. Renal stone risk during space flight assessment and countermeasure validation. USRA/DSLS Bioinvestigator's Workshop Abstract Volume. Annual Meeting. Galveston, TX, 2005 January 10–12.
  9. Jones JA, Whitson P. Genitourinary issues in space medicine. In: Barratt M (ed). Clinical Space Medicine 2005 (in press).
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Acknowledgements

Dr Larry Lipshultz, Department of Urology, Baylor College of Medicine, Adrian Leblanc at USRA and Shannon Melton at Wyle Laboratories.

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