We know that certain health conditions and diseases are sex-specific. Testicular cancer, for instance, is specific to men while uterine cancer occurs only in women. However, physicians should also be aware of certain not-so-obvious diseases that exert sex biases. These diseases—which on the surface may not be expected to affect men and women differently—exhibit differences in symptomatology, presentation, risk factors, prevalence rates, and mortality rates between sexes.

With this in mind, here are seven diseases that you may not know differ between men and women:

---

Infections

Everyone knows that hormone levels vary between men and women, with men harbouring higher serum concentrations of testosterone and premenopausal women exhibiting higher levels of progesterone and estrogen. Notably, these hormone differences can contribute to intriguing pathophysiologic differences between men and women. For instance, because of the anti-inflammatory effects of estrogen, women tend to experience a lower frequency of infection compared with men.

In one study published in the American Journal of Physiology, researchers obtained human nasal cells from adult male and female donors that were then treated with estrogen-like compounds before exposure to the influenza virus to determine whether estrogenic signaling on influenza virus infection affects outcomes. They found that only cells from female donors responded to the compounds and were able to fight off the virus.

---

Autoimmune diseases

Like infection, rates of autoimmune disease also differ among men and women. Some researchers have suggested that women develop autoimmune diseases at a greater prevalence than men due to hormone levels. Because estrogen greatly affects the immune system, women may develop autoimmune diseases like multiple sclerosis and lupus more frequently than men.

According to other experts, women may have evolved a strong immune response to protect developing fetuses. The drawback to this sensitive immune response, however, is that the immune system may overreact, attacking the body and causing autoimmune diseases to manifest.

Still, other researchers have suggested that this disparity may have less to do with estrogen and more to do with testosterone. In several studies, testosterone has been linked to protection against autoimmune diseases. Testosterone reduces the level of B cells, which are lymphocytes that release harmful antibodies. In a study published in Nature Communications, researchers found that testosterone suppresses BAFF, a protein that makes the B cells more viable. Genetic variations in BAFF have been linked to the risk of diseases like lupus.

“We have concluded that testosterone suppresses BAFF. If you eliminate testosterone, you get more BAFF and thereby more B cells in the spleen because they survive to a greater extent,” said coauthor Asa Tivesten, MD, PhD, professor of medicine, Sahlgrenska Academy, University of Gothenburg, Sweden.

---

Pituitary adenomas

On the whole, men usually form larger pituitary adenomas than women. Some researchers have suggested, however, that this difference in size could be due to sociocultural differences between men and women, not biological differences. Specifically, women tend to seek treatment earlier because of more pronounced symptoms such as irregular menstruation or infertility.

Furthermore, pituitary adenomas may affect sexual function in men, which can be an embarrassing problem to discuss with a physician. Consequently, men may delay going to the doctor until their pituitary adenomas are quite large.

---

Stroke

When most healthcare providers think of stroke, drooping of one side of the face and slurred speech instantly come to mind. Nevertheless, women who experience stroke often fail to present with these specific symptoms, which can make the diagnosis more challenging and less timely. Specifically, women who experience stroke often complain of headache, pain in the jaw or neck, and/or feelings of anxiety or confusion.

But stroke doesn’t just affect women differently than men only in terms of symptoms. Risk factors and outcomes also vary between the sexes. In four separate analyses published in Stroke, researchers found that women have unique risk factors for stroke—specifically preeclampsia—and suffer greater disability and significantly higher lifetime risks for stroke and mortality than men.

---

Substance use disorder

Men tend to misuse illicit drugs more often than women, and this difference yields more emergency department visits and overdose deaths in men.

“For most age groups, men have higher rates of use or dependence on illicit drugs and alcohol than do women. However, women are just as likely as men to develop a substance use disorder,” according to the NIH. “In addition, women may be more susceptible to craving and relapse, which are key phases of the addiction cycle.”

---

Depression

In 2010, the global prevalence of major depression was 5.5% in women compared with just 3.2% in men.

Authors of a review article published in the Journal of Psychiatry & Neuroscience suggested that this difference in prevalence may be due to hormone variances between the sexes:

“The fact that increased prevalence of depression correlates with hormonal changes in women, particularly during puberty, prior to menstruation, following pregnancy and at perimenopause, suggests that female hormonal fluctuations may be a trigger for depression. However, most preclinical studies focus on males to avoid variability in behaviour that may be associated with the menstrual cycle. Nevertheless, primate and rodent studies consistently implicate a role for female hormones, such as estrogen, in depression.”

---

Cancer

Men have a 50% chance of developing cancer during the course of a lifetime compared with women who have a 33% chance. Why the difference?

One explanation is that women have an extra copy of certain protective genes, which can control against uncontrolled cell growth. In some cancer types, this one difference could account for up to an 80% difference in cancer frequency.

This story is contributed by Naveed Saleh and is a part of our Global Content Initiative, where we feature selected stories from our Global network which we believe would be most useful and informative to our doctor members.