Twenty-five-year-old research suggested that high levels of testosterone in African American men (as compared to white and Asian men) were partly to blame for incidences of prostate cancer.

But more recent studies suggest that estradiol hormones paint a fuller picture of Black people’s chance of receiving a prostate cancer diagnosis.

Read on for a comprehensive look at the most recent science and news behind this.

Most prostate cancer requires testosterone to survive in the body. In 1941, researchers Huggins and Hodges showed that castration (at the time, this meant actual removal of the testicles) reduced the impact of the disease for men with metastatic prostate cancer.

In the past 80 years or so, a cornucopia of research on testosterone’s interaction with the androgen receptor and subsequent growth stimulation of prostate cancer led to the development of multiple medical treatments for prostate cancer.

For people with high risk disease, androgen deprivation therapy (ADT) typically decreases serum testosterone levels to castrate levels. This is done through oral medications, injectable medications, or surgery to remove the testicles (though this procedure is rarely done today).

It’s important to note that while ADT is quite effective at treating prostate cancer initially, it’s not a curative treatment if used alone. Rather, it’s often used alongside radiation therapy and sometimes in conjunction with surgery when it’s believed that the cancer is curable.

If you’re treated with long-term ADT, it’s common to eventually develop castrate resistance. This is when the cancer finds a way around the reliance on testosterone and is no longer deterred by testosterone deprivation.

The relationship between testosterone levels in Black men and the development of prostate cancer is controversial.

Older studies suggested a possible relationship between higher average testosterone levels in Black men and the development of prostate cancer.

But newer studies show that after age 40, testosterone levels in Black and white men are similar.

A 2006 study found dihydrotestosterone levels (the more potent form of testosterone that’s present in actual prostate tissues) to be about the same for African American and white men.

Population-level studies showed that testosterone levels in younger men tend to correlate with prostate cancer incidence in older men, but these studies didn’t show causation.

There are three estrogen hormones: estradiol, estrone, and estriol.

Role of estradiol

Estradiol is considered the “strongest” of the three.

It has a well-established role in egg maturation and ovulation as well as thickening the uterine lining to allow egg implantation in women.

Role of estrone

Estrone, weaker than estradiol estrogen, is produced in both the ovaries and in fat tissue. It’s the estrogen hormone responsible for most of the effects related to sexual development in young women.

Role of estriol

Estriol is the weakest of the three estrogens and is practically undetectable outside of pregnancy, which is when it serves its main purpose.

It’s often used to treat menopausal symptoms as part of hormone replacement therapy. It may help with hot flashes, vaginal dryness, and even insomnia.

Though estradiol originates in the ovaries for women, in men it can be produced through a process called aromatization. This process basically converts testosterone to estradiol.

In men, estradiol likely plays many roles, including maintaining strong bones, metabolizing glucose, and stabilizing vasomotor symptoms like hot flashes or night sweats. It may also help with brain function.

In male patients treated with estradiol, breast growth (gynecomastia) is a common side effect resulting from the stimulation of estrogen receptors on breast tissue. Some studies have suggested that higher estradiol levels may lead to low libido, as well.

Estrogens work to suppress tumor growth in prostate cancer. In the medical community, interest in using estradiol in addition to standard ADT for prostate cancer treatment is increasing.

A large randomized trial from the United Kingdom in 2021 recently showed that advanced prostate cancer patients treated with estradiol transdermal patches achieved similar levels of castration as with ADT alone.

The findings also revealed no increase in cardiovascular events such as heart attack or stroke, which have been associated with standard ADT treatment.

Importantly, estrogens have been shown to have a significant effect on prostate cancer that has stopped responding to standard ADT. Estrogens may also help prevent some of the known side effects of ADT like hot flashes.

Men on testosterone replacement therapy can sometimes experience elevated estradiol levels when excess testosterone is aromatized, or converted, to estradiol.

Overweight or obese men can also have higher levels of estradiol due to aromatization in the fat tissues. As noted earlier, the role of race is controversial and hasn’t been definitively shown to influence estradiol in either direction.

Rarely, a genetic condition called excess aromatase activity can lead to the acceleration of testosterone conversion. This is characterized by gynecomastia, small testicles, and extreme growth in childhood height.

Studies, including a 2014 report, have shown that African American women have higher follicular fluid estradiol levels throughout the menstrual cycle.

In African American men, there’s conflicting evidence. A 2014 study looking at estradiol and testosterone in both Black and white men found only a modest difference in Black men’s free testosterone levels — that is, they were only slightly higher than white men’s.

In addition, the findings didn’t detect a significant difference in serum estradiol levels between Black and white men.

An older study from 2007 showed higher estradiol levels in Black men compared to white and Mexican American men.

Finally, a 2013 study showed lower estradiol levels in adolescent Black men as compared to white and Hispanic men.

In conclusion, there isn’t enough evidence to support the idea of Black people having higher levels of estradiol hormones than people of other ethnicities.

Unequal access to healthcare has led to generally lower levels of prostate cancer screening, which can, in turn, lead to Black men being diagnosed at a more advanced stage of the disease.

Routine PSA screening with or without a digital rectal exam starting at age 45 is recommended for Black men.

More recently, researchers are especially interested in learning more about how the tumor microenvironment, or the conditions surrounding the cancer, might influence tumor growth or survival.

An increasing body of work, including a 2021 study focusing on racial disparity in prostate cancer, suggests that diabetes, obesity, and even high blood pressure can increase prostate cancer incidence.

Several older studies of predominantly white men have shown no significant association between prostate cancer and estradiol levels.

A 1996 study showed an inverse relationship, meaning that low estradiol levels were associated with higher prostate cancer risk.

While Asian men, in general, are known to have a lower incidence of prostate cancer, rates are increasing in many Asian countries.

While I am not aware of any specific studies looking at estradiol levels in this population, there’s some data to suggest that high soy intake (which contains phytoestrogens) can be beneficial in prostate cancer. Soy intake tends to be high in many Asian countries, so there may be a link there.

As noted earlier, we don’t have evidence that high levels of estradiol contribute to prostate cancer. In fact, several studies have suggested that estradiol may be a treatment for patients with prostate cancer, especially in advanced stages.

That said, estradiol treatment has not yet made its way into prime-time treatment for prostate cancer and is still considered investigational, as its specific role and timing of treatment remains to be worked out in detail.

Dr. Joseph Brito is an ABMS board certified urologist at Yale Medicine, providing general urologic care, with a special focus in minimally invasive surgical techniques and urologic oncology. Dr. Brito completed his residency at Brown University and is fellowship trained in clinical oncology at Yale.