Introduction

As humanity plans for long-duration missions to the Moon and Mars, understanding the unique health risks for a diverse astronaut corps is paramount. The space environment presents multiple hazards, primarily microgravity and high-energy galactic cosmic radiation (GCR), which can impact human physiology in complex ways. This review synthesizes current scientific knowledge to address a critical question: does spaceflight increase the risk of developing gynecological cancers in female astronauts? By examining data from terrestrial, simulated, and spaceflight studies, the authors aim to define the potential risks and identify crucial gaps in our understanding.

Research Objective

This review aimed to provide a comprehensive summary of the research concerning spaceflight and gynecological cancer risk. The primary goals were:

• To review the known effects of the two main space-environmental factors, space radiation and microgravity, on the female reproductive system.
• To evaluate existing in vitro (cell-based) and in vivo (animal) studies related to gynecological cancer development in simulated and real space conditions.
• To identify critical knowledge gaps and outline future research priorities needed to develop effective screening protocols and countermeasures for female astronauts.

Key Findings

The review consolidated evidence from a wide range of studies, revealing a field with more questions than answers, but with several key takeaways:

• There is no direct evidence of increased gynecological cancer rates in the current female astronaut population. However, this conclusion is limited by the small number of female astronauts and their relatively short-duration missions, primarily within the protective magnetic field of Low Earth Orbit.
• Animal models provide a significant cause for concern. In one key study, female mice exposed to simulated GCR (heavy iron ions) showed a dramatically higher incidence of ovarian tumors, with 47% developing unilateral tumors compared to just 14% in the unexposed control group.
• Simulated microgravity has complex and sometimes contradictory effects on cancer cells in vitro. While it can induce apoptosis (programmed cell death) in some cancer cell lines, it also alters key signaling pathways (e.g., PI3K/Akt) involved in cell survival, proliferation, and resistance to chemotherapy.
• Spaceflight is known to cause immune system dysregulation, leading to the reactivation of latent viruses like Epstein-Barr virus (EBV) and cytomegalovirus (CMV). This raises a potential, though unproven, risk for the reactivation of oncogenic viruses like Human Papillomavirus (HPV), the primary cause of cervical cancer.
• A major limitation is the reliance on terrestrial analogs. Ground-based studies cannot fully replicate the unique, chronic, low-dose, mixed-field radiation environment of deep space, making direct risk extrapolation difficult.

Methodology

This publication is a comprehensive literature review and does not present new experimental data. The authors synthesized findings from a broad array of scientific studies, including:

• Organisms/Subjects: Data from human astronaut health monitoring, animal models (primarily mice and rats), and various human gynecological cancer cell lines (ovarian, cervical, endometrial).
• Experimental Conditions: The review analyzed data from actual spaceflight missions on the International Space Station (ISS), ground-based microgravity simulators (e.g., clinostats, Random Positioning Machines), and particle accelerators that simulate components of GCR.
• Key Techniques Analyzed: The paper covers research utilizing a range of techniques, including histology (tissue analysis), molecular biology (gene and protein expression), and systems biology approaches to assess cellular changes and carcinogenesis.

Importance for Space Missions

This review directly addresses a critical health risk for long-duration exploration missions to the Moon and Mars, where astronauts will face significantly higher cumulative radiation doses outside of Earth’s protective magnetosphere. The findings are vital for:

• Informing Medical Standards: The evidence underscores the need to refine medical screening, in-flight monitoring, and post-flight surveillance protocols specifically for female astronauts.
• Countermeasure Development: Identifying the primary risk pathways is the first step toward developing and validating effective countermeasures, which may include optimized spacecraft shielding, radioprotective pharmaceuticals, and targeted dietary interventions.
• Ensuring Crew Health: Protecting the long-term health of an increasingly gender-diverse astronaut corps is essential for mission success and the future of human space exploration.

Knowledge Gaps & Future Research

The authors highlight several critical areas where knowledge is lacking, which must be addressed to ensure astronaut safety:

• The synergistic effects of combined microgravity and space radiation on gynecological tissues are largely unknown and represent a top research priority.
• The long-term impact of using hormonal contraceptives in the deep space environment on cancer risk, drug effectiveness, and overall health is not understood.
• Further research is urgently needed to determine if oncogenic viruses like HPV are reactivated during spaceflight and how this might alter cancer risk.
• There is a significant lack of omics data from female reproductive tissues in NASA’s GeneLab and other open science repositories, which limits our ability to model risks and identify protective mechanisms.

Results

This review consolidates the sparse but concerning evidence regarding gynecological cancer risks associated with spaceflight. While definitive human data is not yet available, the potential threats from radiation-induced tumorigenesis in animal models, cellular dysregulation in microgravity, and immune-mediated viral reactivation are significant enough to warrant a focused, robust research effort. Addressing the identified knowledge gaps is essential for developing the evidence-based medical protocols and countermeasures required to protect the health of female explorers on pioneering missions to the Moon, Mars, and beyond.