Cardiovascular Risks with HRT

At QueerDoc, we used an informed consent model.  Informed consent happens when you can make decisions about your care WITHOUT the input of a mental health professional, if you have the capacity to understand the potential risks and benefits of your treatment.  Using an informed consent model is recommended by many professional bodies associated with gender affirming care.  Unfortunately, most health care providers aren’t very skilled at talking about risk. ^{1, 2, 3}  And if you don’t know the risk, how can you really provide INFORMED consent?

Trying to understand the long-term potential risk of HRT is challenging for many reasons.  A primary reason is we don’t have a lot of research and the research we do have is not high quality or not very applicable.  For today, we will focus on how HRT affects cardiovascular (heart and blood vessel) disease risk.  Because we can’t get enough acronyms, we’ll shorten cardiovascular disease to CVD for the rest of this blog.

CVD risk is complicated, but we know that the following factors can affect your risk of disease AND can be affected by hormones:

• Total body weight
• Total body fat, especially fat around your abdomen (visceral fat)
• Levels of certain types of fats circulating in your blood:
  • Low-density lipids (LDL)
  • High-density lipids (HDL)
  • Total cholesterol (and your ratio of LDL and HDL)
  • Triglycerides
• Increased amounts of homocysteine, which is by-product of protein metabolism

An article published in April of 2019 reviewed the many studies regarding cardiovascular disease risk in trans people. ⁴  You can read the full article online, but I will provide a broad overview here.  I’ve also included a link to the article in the citations at the end of this blog.

Not a lot of studies have been done on CVD risk in trans people, and the studies that have been done often don’t have a lot of people in them, or haven’t followed those people for a long time, so we don’t have a lot of data on long-term outcomes.  This makes them low-quality:  good quality studies include a lot of people to better account for natural variances in the data.  Also, heart disease may take a long time to progress from mild to severe (and risk naturally increases with age) – if a study group isn’t followed for a long time, the study may paint an incomplete picture.

Of the studies that have been done, they have not accounted for other CVD risks which could affect their conclusions about HRT use.  Some of these risks are age, how long the study participants have been taking HRT, obesity, and if the participants smoke (a big CVD risk factor!) They also do not take into consideration things that disproportionately affect transgender people and impact life expectancy, like minority stress, and, sadly, higher rates of HIV infection and suicide.

Additionally, these studies do not reflect the way we prescribe hormones here and now.  A lot of the research was done using different types of estrogen and anti-androgens than what we’re currently prescribing in the United States.  Finally, while the studies may ask the same questions, they vary in how they answer them.  That makes interpreting and applying the research tough!

The take home point is that our research on cardiovascular disease (CVD ) risk in trans people is poor, and there is still a lot to be learned.

Remember all this as you read onwards!  At the same time, studies have shown that HRT reduces stress, improves quality of life, and reduces tobacco use, and these things are heart healthy, reducing your risk of CVD. ^{5, 6}  Like we needed a study to know that!

Based on the review of the literature for trans feminine folx on HRT, here’s what the data suggests:

Changes that increase your risk of CVD:

• You are likely to gain total body weight and your body-fat percentage will likely increase.  This fat is more likely to be stored in your abdominal area.
• Your triglyceride levels will probably go up

Changes that decrease your risk of CVD:

• Your LDL cholesterol and homocysteine levels are likely to fall

What does this mean for heart disease events?

• Heart Attack Probability: Decreased risk of having a heart attack (myocardial infarction).  The amount of this decrease is unknown, but you are lower risk than people with testicles not taking any hormones and higher risk than people with ovaries not taking any hormones
• Stroke Probability: Decreased risk of having a stroke.  The results are really mixed. The data seems to suggest that strokes occur at higher rates than people with ovaries not taking any hormones but at lower rates than people with testicles not taking any hormones
• Blood clots:  Increased risk of having a blood clot (thromboembolic event).  Previously it was thought that the risk might increase as much 20-45 times, but newer studies suggest it is much lower – around 2 times the rate of people with ovaries not taking any hormones and people with testicles not taking any hormones.  Also, this risk is lower than the rate of people with ovaries taking hormones for birth control.

Important bits:

• The TYPE of estrogen taken seems to play a big role in this risk
  1. Say “NO” to ethinylestradiol (common in birth control)
  2. Say “YES” to 17B-estradiol (common in gender care)

• The WAY YOU TAKE your estrogen may or may not be a factor. We used to be certain that it did, but newer data seems to suggest it is the TYPE of estrogen not the HOW you take it
  1. Still the data says patches (transdermal) are the safest

• PROGESTERONE’s role
  1. Say “NO” to non-pregnane progestins (synthetic and common in birth control).  These DEFINITELY increase your risk of blood clots
  2. Say “YES” to micronised progesterone (prometrium) or pregnane derivatives like medroxyprogesterone acetate. These DO NOT increase your risk of a blood clot 

Based on the review of the literature for trans masculine folx on HRT, here’s what the data suggests:

• Taking testosterone can increase your total body weight, which is a risk factor for CVD.
  1. BUT testosterone can also cause an overall decrease in total body fat, which is a protective factor against CVD
  2. Gained weight may be lean muscle mass, which can be protective against heart disease.
• Testosterone often changes some lipid labs:
  1. It can cause higher homocysteine and triglyceride levels and lower HDL levels – all three of these can increase CVD risk 
  2. However, total cholesterol and LDL cholesterol usually don’t increase on testosterone
  3. This means that overall lipid profile changes may not affect CVD risk much 

What does this mean for heart disease events?

• Heart Attack Probability: No change in risk of having a heart attack (myocardial infarction). 
• Stroke Probability: No change in risk of having a stroke
• Blood clot Probability:  No change in risk of having a blood clot

We’re still learning!  This is what we know so far – it’s important to remember that this is based on very limited, poor quality, and not totally applicable data!  This is also only in relation to cardiovascular disease risk, not cancer, osteoporosis, or anything else.  

We do know from high-quality, reproducible research that managing your other individual risk factors for cardiovascular disease makes a huge difference to your overall health! Smoking less or stopping all together, eating healthy whole foods that are less processed and naturally low in sugar, getting regular exercise, maintaining a body weight in balance with your health, reducing your risk of HIV, and improving how you manage stress – all of these decrease your personal risk of cardiovascular disease as you age!!!  If you’re considering HRT, and choose QueerDoc as your provider, we’ll discuss your risks as a part of your care.

1. How Much Information About Adverse Effects of Medication Do Patients Want From Physicians?  Dewey K. Ziegler, MD; Michael C. Mosier, PHD; Maritza Buenaver, BS; et alKola Okuyemi, MD Arch Intern Med. 2001;161(5):706-713. doi:10.1001/archinte.161.5.706
2. Drugs Ther Perspect. 2015 Feb; 31(2): 68–76.  Do physicians communicate the adverse effects of medications that older patients want to hear?  Derjung M. Tarn, MD, PhD,1 Ariela Wenger,1 Jeffrey S. Good, PhD,2 Marc Hoffing, MD, MPH,3 Joseph E. Scherger, MD, MPH,4 and Neil S. Wenger, MD, MPH5
3. Physician Communication When Prescribing New Medications.  Derjung M. Tarn, MD, PhD; John Heritage, PhD; Debora A. Paterniti, PhD; Ron D. Hays, PhD; Richard L. Kravitz, MD, MSPH; Neil S. Wenger, MD, MPH
4. Cardiovascular disease in transgendered people: A review of the literature and discussion of risk. Leighton J September 30, 2019 Review Article https://doi.org/10.1177/2048004019880745
5. E. Coleman, W. Bockting, M. Botzer, P. Cohen-Kettenis, G. DeCuypere, J. Feldman, L. Fraser, J. Green, G. Knudson, W. J. Meyer, S. Monstrey, R. K. Adler, G. R. Brown, A. H. Devor, R. Ehrbar, R. Ettner, E. Eyler, R. Garofalo, D. H. Karasic, A. I. Lev, G. Mayer, H. Meyer-Bahlburg, B. P. Hall, F. Pfaefflin, K. Rachlin, B. Robinson, L. S. Schechter, V. Tangpricha, M. van Trotsenburg, A. Vitale, S. Winter, S. Whittle, K. R. Wylie & K. Zucker (2012) Standards of Care for the Health of Transsexual, Transgender, and Gender-Nonconforming People, Version 7, International Journal of Transgenderism, 13:4, 165-232, DOI: 10.1080/15532739.2011.700873
6. White Hughto JM, Reisner SL. A Systematic Review of the Effects of Hormone Therapy on Psychological Functioning and Quality of Life in Transgender Individuals. Transgend Health. 2016;1(1):21–31. doi:10.1089/trgh.2015.0008