Sex Differences and Sex Steroids Effects in Musculoskeletal Health

Purpose: The aim of this review is to assess the current evidence regarding the impact of relaxin on incidence of soft tissue hip injuries in women.

Methods: A trained research librarian assisted with searches of PubMed, Embase, CINAHL, and SPORTDiscus, with a preset English language filter. The review was completed per the Joanna Briggs Institute (JBI) Manual for Evidence Synthesis methodology. Included studies required assessment of relaxin effects on musculoskeletal health, pelvic girdle stability, or hip joint structures in human subjects. Letters, texts, and opinion papers were excluded.

Results: Our screen yielded 82 studies. Molecularly, relaxin activates matrix metalloproteinases (MMPs) including collagenases MMP-1/-13 and gelatinases MMP-2/-9 to loosen pelvic ligaments for parturition. However, relaxin receptors have also been detected in female periarticular tissues, such as the anterior cruciate ligament, which tears significantly more often during the menstrual cycle peak of relaxin. Recently, high concentrations of relaxin-activated MMP-9 receptors have been found on the acetabular labrum; their expression upregulated by estrogen.

Conclusions: Menstrual cycle peaks of relaxin activate MMPs, which locally degrade collagen and gelatine. Women have relaxin receptors in multiple joints including the hip and knee, and increased relaxin correlates with increased musculoskeletal injuries. Relaxin has paracrine effects in the female pelvis on ligaments adjacent to hip structures, such as acetabular labral cells which express high levels of relaxin-targeted MMPs. Therefore, it is imperative to investigate the effect of relaxin on the hip to determine if increased levels of relaxin are associated with an increased risk of acetabular labral tears.

Breast cancer and osteoporosis are common diseases that affect the survival and quality of life in postmenopausal women. Women with breast cancer are more likely to develop osteoporosis than women without breast cancer due to certain factors that can affect both diseases simultaneously. For instance, estrogen and the receptor activator of nuclear factor-κB ligand (RANKL) play important roles in the occurrence and development of these two diseases. Moreover, chemotherapy and hormone therapy administered to breast cancer patients also increase the incidence of osteoporosis, and in recent years, neuropeptide Y (NPY) has also been found to impact breast cancer and osteoporosis.Y1 and Y5 receptors are highly expressed in breast cancer, and Y1 and Y2 receptors affect osteogenic response, thus potentially highlighting a potential new direction for treatment strategies. In this paper, the relationship between breast cancer and osteoporosis, the influence of NPY on both diseases, and the recent progress in the research and treatment of these diseases are reviewed.