Disclaimer: This article is intended solely for informational and educational purposes only. It does not constitute medical advice.
Postoperative nausea and vomiting (PONV) is a common complication of anesthesia that can delay recovery and cause significant patient discomfort. Women experience PONV more frequently than men, making female sex an established risk factor (1). Yet the biological reasons for this difference remain uncertain. One possible explanation involves estrogen and testosterone, which may affect susceptibility to postoperative nausea through different physiological mechanisms.
Recent research has strengthened the possibility that sex hormones contribute to PONV risk. Soloniuk et al. compared transgender patients receiving hormone therapy with cisgender patients undergoing similar surgical procedures (2). Transgender men receiving testosterone were slightly less likely to require additional antiemetic medication following surgery than cisgender women, while transgender women receiving estrogen were more likely to require these medications than cisgender comparison groups. The differences associated with estrogen therapy were approximately 10 to 14 percentage points, compared with about 4 percentage points for testosterone. Although these findings suggest opposing hormonal associations, these groups may differ in clinical characteristics beyond hormone exposure. Furthermore, the effects of administered hormones may not directly reflect those of naturally occurring hormones, limiting conclusions about their independent effects on PONV.
Estrogen may contribute to nausea through its effects on gastrointestinal function. Al-Shboul et al. demonstrated that estrogen relaxes gastric smooth muscle through a mechanism involving nitric oxide and cyclic guanosine monophosphate (3). Since coordinated gastric contractions are necessary for normal stomach emptying, this effect could potentially slow gastric motility and increase susceptibility to nausea. However, the study examined gastric muscle activity rather than postoperative symptoms. While the findings provide a possible physiological explanation, they do not establish whether estrogen-related changes in gastric motility meaningfully increase postoperative nausea and vomiting risk.
The relationship between estrogen and PONV becomes less clear when examining natural hormonal fluctuations. Estrogen concentrations vary throughout the menstrual cycle, particularly around ovulation, prompting researchers to investigate whether postoperative nausea follows a similar pattern. Honkavaara et al. reported increased retching and vomiting during the periovulatory phase following middle ear surgery (4). However, a more recent prospective study by Narayanan et al. found no significant association between preoperative estrogen concentrations and PONV among women undergoing diagnostic laparoscopy and hysteroscopy (5). These conflicting findings suggest that estrogen levels alone may not reliably predict postoperative nausea. Differences in surgical procedures, hormonal fluctuations, and other perioperative factors may influence the relationship.
Testosterone's potential role in PONV is less understood. One proposed explanation for its association with lower antiemetic requirements involves its ability to suppress estrogen activity. Testosterone can reduce endogenous estrogen production and alter estrogen receptor expression, potentially limiting physiological responses associated with estrogen exposure (2). This suggests that testosterone may influence PONV indirectly rather than exerting a direct antiemetic effect. However, the available clinical evidence does not establish which mechanism is responsible, and direct investigations measuring testosterone concentrations alongside postoperative symptoms remain limited.
Overall, estrogen and testosterone may contribute to the higher incidence of PONV in women, but the evidence remains limited. Studies of hormone therapy have found differences in postoperative antiemetic use, while studies measuring naturally occurring estrogen have not consistently found the same association. These findings support further investigation of the relationship between estrogen, testosterone, and postoperative nausea and vomiting.