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Hydrochlorothiazide Side Effects: Skin Cancer and More!

Few health professionals think hydrochlorothiazide side effects are serious. But a Danish study links HCTZ with squamous cell skin cancer.

The American Heart Association and the American College of Cardiology have issued guidelines about hypertension. The experts state that “normal” blood pressure is “Less than 120/80.” You have “elevated” blood pressure if your upper number (systolic BP) is between 120-129. Stage 1 hypertension occurs when systolic BP is between 130-139 or diastolic BP is between 80-89. That means at least half of all adults in the United States now have high blood pressure. The chances are good that many of them will be prescribed thiazide diuretics as first line therapy. But what are hydrochlorothiazide side effects? Is skin cancer one of them?

Is One of the Hydrocholorothiazide Side Effects Skin Cancer?

Now that it is summertime, we should all pay attention to protecting ourselves from sunburn. That is easier for some people than for others.

People with fair skin, red hair and blue or green eyes probably already know they are more prone to painful red skin if they venture out in the sun. But what about the nearly 10 million people taking the common blood pressure pill hydrochlorothiazide? Another 6.5 to 7 million take it in a combination antihypertensive medicine and may not even realize they are on it.

Why does that matter? Hydrochlorothiazide (HCT or HCTZ) makes the skin more sensitive to sunburn. Studies in Iceland (Journal of the American Academy of Dermatology, March 2021) and Australia (Basic & Clinical Pharmacology & Toxicology, Oct. 2020) have found that people taking HCT long term have a higher risk for skin cancer.

Ignoring Hydrochlorothiazide Side Effects:

Because HCTZ is prescribed so often to so many it is easy for healthcare providers to take this drug for granted. It is perceived by many to be super safe.

There are, however, a number of hydrochlorothiazide side effects. More about that shortly. One that may not be mentioned very often is an increased sensitivity to sunlight. It might be perceived by health professionals as a minor adverse reaction. But this reader suggests otherwise:

Skin Cancer Can Be a Big Deal:

“I am devastated to learn that the risk of skin cancer can be increased by hydrochlorothiazide. I have been on this blood pressure medication since around 2007.

“In 2016 I was diagnosed with squamous cell carcinoma, and I had to have five surgeries. The left side of my nose was removed. My septum collapsed during surgery, so they had to remove cartilage from my ear to rebuild my septum.

“It was truly a nightmare and the most painful thing I have ever had to go through. I was scared to death.

“I am so upset to find out that HCTZ leads to this type of skin cancer. No one ever told me.”

Hydrochlorothiazide Side Effects: Skin Cancer?

Another reader shared this story about HCTZ and skin cancer:

Q. For about two decades, I took the diuretic hydrochlorothiazide (HCTZ) to prevent recurring kidney stones. I’d had five years in a row dealing with these stones. Changing my diet and increasing my fluid intake didn’t help but the drug did.

A Danish study came out noting an increased skin cancer risk from HCTZ. My basal cell carcinoma and squamous cell carcinoma lesions were removed eight years into taking this drug.

The melanoma lesion on my scalp appeared the following year. By then, it had spread to my lungs and bones. When the study came out, my oncologist discontinued the HCTZ. This was many years into my cancer journey, though. Luckily, I am in my second remission with immunotherapy every three weeks for the last five years.

The Danish Study:

The Danish study you mention does indeed link thiazide diuretics with squamous cell carcinoma (Journal of the American Academy of Dermatology, April, 2018). This type of skin cancer is linked to excessive sun exposure. HCTZ sensitizes the skin to ultraviolet radiation from the sun. By making the skin more vulnerable to sunlight, skin damage and sunburn is more likely.

The study included 80,000 Danish citizens with non-melanoma skin cancer. Those who took the highest dose of hydrochlorothiazide for the most years were seven times more likely to develop squamous cell carcinoma than people who took no HCTZ. The scientists looked at other blood pressure medications and did not find any similar associations.

The UK Database:

More recently, investigators have confirmed the connection between HCTZ and a higher risk of squamous cell skin cancer (British Journal of Dermatology, Feb. 20, 2021). The Swiss and US researchers relied on a UK primary-care database. We doubt that many health care professionals are aware of this research.

The FDA Warns About HCTZ and Skin Cancer:

On August 20, 2020, the FDA strengthened its warning for people taking HCTZ. The agency now urges patients on this BP medicine to:

“protect their skin from the sun and undergo regular skin cancer screenings.” 

Many health care providers are unaware that blood pressure medications can make the skin more vulnerable to sun damage. Those that are aware of this risk may shrug it off as a relatively minor problem. That’s because they consider both squamous and basal cell carcinoma as relatively easy to treat.

Physicians should be alerting patients to hydrochlorothiazide side effects in general and this potential complication in particular. If you are taking HCTZ by itself or in combination with another BP medicine have you been encouraged to 1) to be especially careful about protecting your skin from the sun’s rays and 2) get regular skin cancer screenings?

Squamous Cell Carcinoma:

When most people think about common cancers they immediately imagine breast cancer, lung cancer, prostate cancer and colon and rectum cancer. According to the American Cancer Association, the projections are that in 2024 there will be:

313,510 cases of breast cancer
234,580 cases of lung cancer
299,010 cases of prostate cancer
152,810 cases of colorectal cancer

It comes as a total shock to learn that the American Academy of Dermatology estimates that:

“Incidence rates

  • Skin cancer is the most common cancer in the United States.
  • Current estimates are that one in five Americans will develop skin cancer in their lifetime.
  • It is estimated that approximately 9,500 people in the U.S. are diagnosed with skin cancer every day.
  • It is estimated that the overall incidence of BCC [basal cell carcinoma] increased by 145% between 1976-1984 and 2000-2010, and the overall incidence of SCC [squamous cell carcinoma] increased 263% over that same period.”

According to the Skin Cancer Foundation:

  • Basal cell carcinoma (BCC) is the most common form of skin cancer. An estimated 3.6 million cases of BCC are diagnosed in the U.S. each year.
  • Squamous cell carcinoma (SCC) is the second most common form of skin cancer. An estimated 1.8 million cases of SCC are diagnosed in the U.S. each year.

Most people do not worry much about skin cancer unless there is a diagnosis of melanoma. They assume that squamous cell carcinoma is not that big a deal. Although squamous cell carcinoma (SCC) is often successfully treated with surgery, it can occasionally be lethal.

An article in JAMA Dermatology (May, 2013) noted:

“Cutaneous squamous cell carcinoma [CSCC] carries a low but significant risk of metastasis and death. In this study, patients with CSCC had a 3.7% risk of metastasis and 2.1% risk of disease-specific death.”

Hydrochlorothiazide Side Effects and Squamous Cell Carcinoma:

The Danish researchers have been concerned about the link between hydrochlorothiazide and squamous cell carcinoma for some time. They reported in the Journal of Internal Medicine (Oct. 2017) that:

“Hydrochlorothiazide use is strongly associated with an increased risk of lip cancer.”

They described it as a “clear dose-response effect.” In other words, the greater the exposure to the drug the more serious the risk.

In their latest publication, they note:

“Recently, we reported a strong association between use of the diuretic hydrochlorothiazide (HCTZ) and squamous cell carcinoma (SCC) of the lip. We found a clear dose-response pattern, with an estimated 7-fold increased risk of SCC lip cancer with cumulative use of ≥100,000 mg HCTZ. Our findings were in line with the results of previous studies from the United States (US) and the recent classification of HCTZ as ‘possibly carcinogenic to humans’ (Group 2B) by the International Agency for Research on Cancer (IARC). As HCTZ is among the most widely used drugs in the US and western Europe, a carcinogenic effect of HCTZ would have a considerable impact on public health.”

The authors conclude:

“In conclusion, given the considerable use of HCTZ worldwide and the morbidity associated with NMSC [non-melanoma skin cancer], a causal association between HCTZ use and NMSC risk would have significant public health implications. The use of HCTZ should be carefully considered, as several other antihypertensive agents with similar indications and efficiency are available, but without known associations with skin cancer.”

Melanoma Is Scary!

The American Academy of Dermatology (AAD) states:

“It is estimated that 200,340 new cases of melanoma, 99,700 noninvasive (in situ) and 100,640 invasive, will be diagnosed in the U.S. in 2024.”

Melanoma gets attention. That is because it can be a hard-to-treat cancer and it can kill. The AAD goes on to note:

“Melanoma rates in the United States have been rising rapidly over the past 30 years — doubling from 1982 to 2011 — but trends within the past decade vary by age. There has been a 31.5% increase between 2011 and 2019.”

Thiazide Diuretics and Melanoma?

The link between thiazide diuretics and melanoma is controversial. A review of the medical literature offers this conclusion (Journal of Clinical Medicine Research, April, 2019):

“In this meta-analysis of observational studies, we found significant association between the use of thiazide diuretics and the risk of SCC [squamous cell carcinoma]. There were marginally significant associations between thiazide use and the risk of BCC [basal cell carcinoma] and MM [malignant melanoma].”

A connection between thiazide diuretics and melanoma is uncertain. A study from South Korea has even suggested that HCTZ might “have a chemopreventive effect against the development of melanoma” (Korean Journal of Internal Medicine, July, 2020).

But more recent research suggests that there could be a connection between thiazide diuretic use and melanoma (JID Innovations, May 2024). This meta-analysis reviewed 42 studies involving over 40 million participants. Hydrochlorothiazide wasn’t the only blood pressure pill linked to skin cancer. Other diuretics were also found to increase the risk for squamous cell carcinoma.

Some Practical Tips Regarding Drugs and Sun:

Many people take blood pressure pills daily for decades. If they are not warned to protect themselves from ultraviolet radiation, they may be putting themselves at risk for skin cancer.

Other medications can also sensitize the skin to the sun’s rays. That includes several types of antibiotics, nonsteroidal anti-inflammatory drugs (NSAIDs), statins, antihistamines and some heart medications.

Sunscreens help protect people from sunburn. It is less clear that they prevent skin cancers in people taking photosensitizing medications. Despite the proliferation of high SPF skin creams and sprays, rates of skin cancer have been rising steadily.

Here are some tips from the Skin Cancer Foundation:

  • Minimize exposure to UV radiation by staying under cover between 10 am and 2 pm.
  • Shield your skin with protective clothing and a wide-brimmed hat.
  • Put an effective sunscreen on any exposed skin, including the backs of the hands, ears, the back of the neck and the tops of the feet.
  • Lips also need protection! Thiazide diuretics have been linked to a higher risk of lip cancer (Cancers, May 2022).
  • Ask a dermatologist to do a whole-body skin review every year.

Health professionals, including nurses, dentists, pharmacists and physicians, should warn patients taking thiazide diuretics or other photosensitizing medications that these could increase the risk for sun damage. Minimizing that risk should also help reduce the chance of developing skin cancer.

The People’s Pharmacy Perspective:

Hydrochlorothiazide is considered very safe by most physicians. This diuretic is often the first line treatment for high blood pressure. What is especially concerning is that many patients don’t even realize they are taking HCTZ. That’s because it is frequently added to another drug such as an ACE inhibitor a beta blocker or an ARB. For a list of drugs containing hydrochlorothiazide, please visit this link.

Other Hydrochlorothiazide Side Effects:

There are a surprising number of hydrochlorothiazide side effects that often go unmentioned. They include electrolyte imbalances, elevated blood sugar, raised uric acid levels, muscle cramps, irregular heart rhythms, dizziness, elevated cholesterol levels, and dry eyes.

To learn more about hydrochlorothiazide side effects, visit this article:

Hydrochlorothiazide (HCTZ) Side Effects, Complications and Gout!

Share your own story about hydrochlorothiazide side effects in the comment section below. If you have done well with this drug we would like to hear from you as well. If you think this information is helpful, please share it with friends and family by clicking on the email icon at the top of this page or sending it via Facebook or Twitter.

Would you like to learn about other medications to help control hypertension or discover some non-drug strategies? Here is a link to our eGuide to Blood Pressure Solutions.

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About the Author
Joe Graedon is a pharmacologist who has dedicated his career to making drug information understandable to consumers. His best-selling book, The People’s Pharmacy, was published in 1976 and led to a syndicated newspaper column, syndicated public radio show and web site. In 2006, Long Island University awarded him an honorary doctorate as “one of the country's leading drug experts for the consumer.”.
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Citations
  • Adalsteinsson JA et al, "Association between hydrochlorothiazide and the risk of in situ and invasive squamous cell skin carcinoma and basal cell carcinoma: A population-based case-control study." Journal of the American Academy of Dermatology, March 2021. DOI: 10.1016/j.jaad.2020.08.025
  • Daniels B et al, "Risk of squamous cell carcinoma of the lip and cutaneous melanoma in older Australians using hydrochlorothiazide: A population-based case-control study." Clinical Pharmacology & Toxicology, Oct. 2020. DOI: 10.1111/bcpt.13463
  • Pedersen SA et al, "Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark." Journal of the American Academy of Dermatology, April, 2018. DOI: 10.1016/j.jaad.2017.11.042
  • Schneider R et al, "Risk of skin cancer in new users of thiazides and thiazide-like diuretics: a cohort study using an active comparator group." British Journal of Dermatology, Feb. 20, 2021. DOI: 10.1111/bjd.19880
  • Schmults CD et al, "Factors predictive of recurrence and death from cutaneous squamous cell carcinoma: a 10-year, single-institution cohort study." JAMA Dermatology, May, 2013. DOI: 10.1001/jamadermatol.2013.2139
  • Pottegård A et al, "Hydrochlorothiazide use is strongly associated with risk of lip cancer." Journal of Internal Medicine, Oct. 2017. DOI: 10.1111/joim.12629
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