The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans.
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A study that assessed pain in patients who underwent arthroscopic anterior cruciate ligament (ACL) reconstruction at an outpatient facility in the United States did not find sex differences in pain at the immediate postoperative evaluation.398 However, on the first day after surgery, females had higher mean VAS pain scores than males. Rosseland345,346 assessed pain immediately after and 1-year after an arthroscopic ACL procedure. Two hours after the procedure, 84% of the females reported at least moderate pain compared with 57% for men.
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Overall, each study reported sex differences in at least one pain outcome, but, similar to heat pain, discrepancies among pain outcomes occur between indices of cold pain within studies. For example, Jones et al205 observed sex-related differences for cold pain tolerance but not threshold. Based on the present set of studies, it appears that sex differences in cold pain are consistent, particularly for suprathreshold measures such as tolerance and pain ratings.
Sex hormones can affect disease pathophysiology, which can affect disease-related pain. For example, the effects of estrogens on bone deposition and cartilage homeostasis could influence the development of articular pathology and pain.400 Of more direct relevance to pain are the hormonal contributions to inflammation. In general, women show a heightened inflammatory response compared with men.394 Although beneficial for wound healing and response to infection, this more robust inflammatory response places women at significantly greater risk for a variety of painful inflammatory autoimmune conditions, including rheumatoid arthritis, osteoarthritis, and systemic lupus erythematosus. The inflammatory response to various triggering events involves plasma extravasation, chemotactic attraction of leukocytes, and, in turn, stimulated release of inflammatory cytokines and growth factors.
Furthermore, duplications of the SOX3 locus were detected in three cases of 46,XX testicular DSD10). SOX3 analysis can be considered the next step for the diagnosis of 46,XX SRY-negative testicular DSD with normal copies of SOX9. A family study recently reported that 46,XY persons with a 178 kb duplication in a region about 500 kb upstream of SOX9 were completely normal fertile males, whereas 46,XX SRY-negative persons in the same family with duplications were clinically infertile males6). In this report, two of the three paternal cousins of their probands are known as infertile and the two probands share the same paternal haplotype for the SOX9 region, confirming the possibility that the father was indeed the carrier of the same triplication. Therefore, we should investigate family members of 46,XX male patients caused by SOX9 duplication. The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare condition with an estimated prevalence of one in 20,000 males1).