Does Melanoma Hit Men Harder?

Ever expected a disease to defy gender equality? Skin cancer is not supposed to discriminate, but melanoma seems to play favorites. Malignant melanoma is the fifth most common cancer worldwide.^[1] It is the deadliest type of skin cancer, and has a marked ability to spread to other sites in the body.^[1] While both men and women are at risk, research show the troubling trend of both higher risk and worse outcomes seen among men.^[2] In fact, men with melanoma are 1.5 times more likely to die, compared to women with melanoma.^[2] So, why are men losing the battle against melanoma more often? Is it genetics, late diagnoses, or a reluctance to wear sunscreen? Read along to find out all the answers, because when it comes to skin cancer, knowledge is not just power, it is survival.

Suspicious melanoma lesion: An irregular, dark pigmented spot with uneven borders, emphasizing the need for early detection and skin cancer screening

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Can you spot the cancerous mole?

Understanding the Risk Factors

A. Behavioral and Lifestyle Influences

Sun exposure

Different patterns of sun exposure are found to be associated with melanoma to varying degrees. Research evidence show that chronic sun exposure, which is when you are exposed to sun almost on a daily basis, does not increase your risk of getting melanoma.^[3] In contrast to this, melanoma is strongly linked with intermittent sun exposure, which is when people spend most of their time indoors but get intense sun on weekends or vacations, often resulting in sunburns.^[4]

Different methods of sun protection are found to lower melanoma risk in different amounts. Sunscreen provides lower protection compared to other methods such as seeking shade and using clothes to protect skin from the sun.^[4]

Delayed medical attention

“Skin awareness” plays a major factor in discovering melanoma. Women are more likely to pay attention to their skin, do self-examinations and visit a doctor at the slightest concern, which leads to early diagnosis.^[5] Similar to any cancer, the earlier you can diagnose melanoma, the better the treatment outcomes will be. Furthermore, the site of melanoma shows a difference based on gender. Women get it commonly on legs while men get it most of often in the trunk area, which is harder to see, leading to late diagnosis.^[4]

B. Biological and Hormonal Differences

Role of estrogen and other hormones

Role of sex hormones in melanoma outcomes is an interesting area, as lots of research have provided different conclusions. Sex hormones like estrogen and testosterone influence immune responses differently; estrogen (female sex hormone) boosts immunity, while testosterone (male sex hormone) weakens it. In melanoma, estrogen may reduce tumor growth, whereas testosterone increases aggressiveness.^[5]

Immune response variation

It is a well-researched finding that women in general have stronger immune systems than men.^[6] This offers women a better fighting chance against melanoma, as the immune system is the major contributor to detecting and destroying melanoma cells. This explains why women have better outcomes compared to men in fighting melanoma.

C. Other risk factors

Atypical mole syndrome

Atypical mole syndrome is a condition where you have many common moles as well as unusual or atypical moles.^[7] People with atypical mole syndrome have a 10.7% risk of developing melanoma compared to 0.62% in others.^[1] Furthermore, if two or more relatives have dysplastic moles and melanoma, the risk approaches 100%.^[1] Men show a higher rate of atypical mole syndrome, which may ultimately contribute to higher risk of men developing melanoma.^[7]

Genetic factors

While females have two X chromosomes, males have one X chromosome and one Y chromosome. Y chromosome is smaller than X, and carries a lot less genes. Some of these X linked genes which are seen in excess in females are believed to be protective factors against melanoma in females.^[4] For example the PPP2R3B gene (found on the X chromosome in women and the Y chromosome in men) is less active in men and linked to worse outcomes in melanoma.^[9]

Key Research Insights

As explained above, estrogen can improve the outcome of melanoma, due to its action via G protein coupled estrogen receptor (GPER). Activation of GPER results in increased pigmentation of cells and increased HLA cell surface protein expression, and these two factors are helpful for the body’s immune system to detect these abnormal melanoma cells.^[5] As women have more estrogen, this mechanism plays to their advantage. Researchers found that activating GPER with a drug that mimic action of estrogen slowed melanoma growth and improved immunotherapy effectiveness.^[5] This brings new hope for men with melanoma to increase efficacy of their treatment.

Interestingly, obese men with melanoma have better survival rates, possibly due to higher estrogen levels from fat tissue.^[8] These findings further suggest that GPER-activating drugs could enhance melanoma treatment, especially in men, by improving immune response and making immunotherapy more effective, offering hope for better outcomes in more patients.

Closing the Gap: Prevention and Treatment

A. Prevention Strategies

Sun protection

Melanoma prevention starts with sun safety. Wearing sunscreen (SPF 50+), protective clothing, and avoiding excessive sun exposure, especially during peak hours are major steps in melanoma prevention. Avoiding mid-day sun exposure and tanning beds will keep your skin safe.^[1] Male targeted grooming products can encourage men to protect themselves and bring awareness.

Routine skin checks

Early detection is just as crucial to beat melanoma. Routine skin checks help catch melanoma early when it is most treatable. Public health campaigns can educate communities on melanoma risks, warning signs, and the importance of regular skin checks, making early detection a shared responsibility. Furthermore, loved ones and partners can play a vital role in spotting suspicious moles in hard-to-see areas, encouraging doctor visits, and reinforcing sun-safe habits. These steps are especially important when it comes to men, who are generally less concerned about minor skin changes.

B. Advancing Treatment Options

Early detection makes it possible to remove the skin cancer surgically, but in advanced stages the options are limited. Melanoma is resistant to both chemotherapy and radiotherapy, which are the well-known modalities of cancer treatment.^[10] This highlights the need of new treatment options to achieve better outcomes in patients with melanoma. Currently, several new therapies are emerging, bringing hope to fight against melanoma.

Hormonal therapies

Recent research highlights the role of estrogen and GPER activation in melanoma treatment. Estrogen enhances immune response and slows tumor growth, suggesting that GPER-activating drugs could offer a new therapeutic approach, especially for men who naturally have lower estrogen levels. These drugs may boost immune system activity and improve melanoma outcomes when combined with existing treatments. A recent study shows that LNS8801 (a clinical GPER agonist) reduces the rate of growth of melanoma, giving practical evidence to the theory.^[11]

Gender-Specific Immunotherapy

Men and women respond differently to immunotherapy due to hormonal and immune system variations. Therefore, men may benefit from hormone-based therapies alongside immunotherapy, while women’s naturally stronger immune responses may allow for different dosing or treatment combinations. Gender-specific strategies could revolutionize melanoma treatment, ensuring better outcomes for all patients.

C. Educating the Next Generation

As lifetime sun exposure is a major risk factor, prevention should start as early as possible. This can be achieved by instilling lifelong sun safety habits in children via schools and community programs. Early education encourages responsible behaviors from a young age. By making sun safety a routine practice, children are more likely to carry these habits into adulthood, ultimately reducing their long-term risk of melanoma.

Conclusion

So, it is clear that melanoma does not play fair; melanoma hits men harder. The good news is, melanoma can be prevented by easy steps like early detection through routine skin checks and practicing sun safety habits. Also, new treatment options like GPER-activating drugs and personalized immunotherapy are offering fresh hope, especially for men. Educating the next generation about sun protection is what we should do today to prevent melanoma tomorrow. It’s time to take action; prioritize sun safety, get regular skin checks, and support the fight against melanoma by spreading awareness.