On Transgender Day of Visibility, we came across a number of relevant articles on the need for better representation of the Transgender community in various spheres of life.

Invariably, our attention turned towards their representation, inclusion & access to healthcare, especially with respect to kidney disease. This basic thought drove us to present you with evidence based insight into the risk & prevalence of kidney disease in the Trans community that can be linked to Gender affirmation treatments.

GENDER AFFIRMATION TREATMENTS & WHY TRANSGENDER PERSONS SEEK THEM?

First, let us explain two terms relevant to this topic that are often confused for each other, but in reality, are two separate concepts. These are “Sex” of a person and their “Gender”.

“Sex” of a person refers to a binary identity assigned at birth (male or female) based on external anatomic characteristics. This is what drives the necessary physiologic behaviour in the body that determines the natural hormonal & physical changes at biologic maturity. “Gender”, by contrast, refers to the psychologic, social, and cultural identity that a person displays while growing up.

Based on these definitions, in cis-gender persons, the “Sex” assigned to them at birth is in congruence with their “gender identity”. Conversely, in Transgender people, the “sex” they were assigned at birth does not reflect their own internal “gender identity” optimally. To minimize this mismatch, transgender persons seek out what we call Gender Affirming Treatments.

Such gender affirming methods typically include a slew of plastic reconstructive surgeries on reproductive organs & external genitalia with subsequent hormonal therapy. These pave the way for near-congruence between a Trans person’s internal gender identity and external gender expression.

CAN GENDER AFFIRMING TREATMENTS CAUSE KIDNEY DISEASE IN TRANSGENDER INDIVIDUALS? HOW?

Gender affirming methods typically include a slew of plastic reconstructive surgeries on reproductive organs & external genitalia with subsequent hormonal therapy. These methods help a transsexual individual achieve a better-matched external gender expression and eliminate gender dysphoria. However, on the flip-side, there is strong research evidence (referenced below) how these techniques may come with their own set of risks to both heart & kidney health.

I. PLASTIC / RECONSTRUCTIVE SURGERY (SEX REASSIGNMENT SURGERY)

“Sex-reassignment surgery” includes re-shaping the naturally existing external genitals into a form with the appearance of, and as far as possible, the function of genitals of desired post-transition gender. The technical name for this procedure is Phalloplasty.

Whether it is a male-to-female transition or vice versa, it involves a “re-sizing operation” on the urine outflow tract (urethra) within the genitals. This is a complex surgery that has its own set of potential complications. Most commonly, patients present with narrowing down of the urethra along sites of operation. (1) This has been reported in both transgender women (2) & transgender men (3). The technical name for this condition is Urethral Stricture. This can happen because of scar formation or skin contracture at the surgical site in course of healing. (2)

WHY IS THIS A CONCERN?

Urethral stricture is a concerning complication with regards to kidney health. Patients with this condition experience difficulty in urinating due to narrowed opening of the urethra. If left untreated over the years, it can cause urine retention with back-pressure on kidneys as a consequence. This can lead to a condition called “Hydronephrosis” (image below).

As the image above shows below, urine retention causes back pressure of urine on kidneys at the site of Renal Pelvis (where ureter starts). This presses over delicate kidney filters. Lack of treatment over time leads to Chronic Kidney Disease & Kidney failure.

IS THE URETHRAL STRICTURE TREATABLE?

Yes. If the patient presents with urethral narrowing with difficulty in urination early on, the surgeon can:

1. 1. Attempt to widen the narrowed zone(s) with a dilator under local anesthesia.
   2. Perform urethrotomy (cutting open the blockage with a scope)
   3. Remove the stricture by open surgery

To prevent these complications altogether, many surgical teams place a sterile bougie within the reconstructed urethra right after the phalloplasty. This is to prevent narrowing of the urinary opening & keep the new urethra patent (open) upon surgery. Further, training patients to conduct gradual, intermittent self-bougination afterwards is also effective in preventing strictures. (2)

It is still advisable for all transsexual members of the community to be vigilant with any symptoms of blockage to urinary outflow. Should this occur, they should report to their medical teams without delay.

II. HORMONAL THERAPY

Along with reconstructive surgeries, hormonal therapy as per desired gender expression forms an integral part of gender affirmation.

Before we can get to the specifics of transgender hormonal therapy and how these could adversely impact your kidneys, here’s a short crash course on non-reproductive effects of gender-specific sex hormones.

GENDER, SEX-HORMONES & KIDNEY HEALTH

Most readers here will know about the specific naturally-occurring sex hormones – Oestrogen (in females) and Testosterone (in males). These Sex hormones are key regulators of our sex and external gender expression.

But did you know every human has BOTH Oestrogen and Testosterone circulating in their bloodstream?

In fact, it is the precise control over the “Ratio” (balance) between Oestrogens & Androgens (collective name for Testosterone & its subtypes) in the bloodstream that contributes towards defining sex-specific traits of an individual. So healthy females have high Oestrogen & low androgen content in their bloodstream. It is the opposite in healthy males.

These are called sex-hormones for their differential presence & roles in binary sexes. But these don’t just control your reproductive health & behaviour. These hormones have significant impact on your heart health via their action on blood vessels, among other things. Since heart health & kidney health are closely inter-linked, the indirect impact of these hormone levels on kidney health carries equal clinical relevance.

RESEARCH EVIDENCE SUGGESTS:

In adult males, normal testosterone hormone or testosterone replacement therapy tightens and narrows blood vessels, increase platelet clumping & promote fat deposition over internal organs.

These actions contribute towards High blood pressure, High cholesterol (deranged lipid profile), Obesity & Insulin resistance (Type 2 Diabetes mellitus) — (4)

All the above a known strong risk factors for both Heart and Kidney disease. In addition, testosterone has a worsening impact on both pre-existing heart and chronic kidney disease as well. (5)

In adult pre-menopausal females, normal levels of Oestrogen in blood keeps blood vessels relaxed, dampens release of chemicals like Renin & Angiotensin-II that otherwise raise blood pressure within kidneys and reduces inflammation. This keeps blood vessels healthy, lowers blood pressure and is a protective factor in heart & kidney disease. (4)

Conversely, in women who have hit menopause, their Oestrogen content in blood falls below normal levels. This reverses all the favourable actions of Oestrogen. Plus, it also gives an upper hand to the baseline testosterone present in every healthy female otherwise. Together, these hormonal changes contribute to sustained high blood pressure. (4) If uncontrolled, it can cause kidney damage in due course.

As explained in the section above, sex hormones affect heart and kidney health in both cis-males and cis-females.

What’s different with Transsexual individuals is that hormone therapies aim to “block or reverse what’s endowed by birth and induce the desired form via external supplements”. To put it simply, the body is taken aback by such therapies that basically appear to ask it to “go against the flow”. Hence, the effects are likely to be more pronounced.

SO, WHAT DOES SUCH HORMONE THERAPY ENTAIL?

For Transgender Women (male-to-female transition), this is called Feminizing hormone therapy. Here, the aim is to decrease the pre-transition testosterone levels in the bloodstream to the normal female range (30-100 ng/dL). This decrease must not be a “relative decrease”. This means, the patient must be treated to produce less testosterone hormone naturally without having to supply higher-than-normal, mega-doses of Oestrogen hormone supplement.

The hormone squad apt for this job include:

1. 1. An Anti-androgen to dampen natural Testosterone secretion
   2. An Oestrogen supplement to raise blood levels of Oestrogen to the normal female range.

For Transgender Men (female-to-male transition), the treatment is termed Masculinizing Hormone therapy. The clinical target is to increase Testosterone levels in bloodstream to normal male physiological range. This comes to around 300-1000 ng/dL.

The hormone soldier that can handle this job is:

1. 1. A Testosterone hormone supplement like Testosterone undecanoate. This raises blood levels of testosterone and automatically dampens the natural secretion of Oestrogen hormone. So, there is no immediate need for an added Oestrogen-blocker in most cases.

Now, the urgency to attain a desirable gender expression at the earliest is perfectly understandable. This is especially true for those experiencing severe gender dysphoria. But in a bid to feel better in the shortest possible time frame, going overboard with hormonal therapy invites a slew of health complications.

Find below the list of complications that can potentially cause kidney disease.

Similar to cis gendered individuals as explained above, most of these complications of long-term Hormone Therapy are mediated via effects on blood vessels, blood composition and blood flow.

Complications of feminizing hormone therapy (6) that can increase your risk of getting kidney disease may include:

• • A blood clot in a deep vein (deep vein thrombosis)
  • High triglycerides, a type of fat (lipid) in your blood
  • High blood pressure (hypertension)
  • Type 2 diabetes
  • Cardiovascular disease
  • Weight gain

Testosterone therapy in Trans Men is relatively better tolerated than feminizing hormone therapy in trans women in terms of blood vessel related complications. Nevertheless, we list here the relevant the adverse effects of Masculinizing hormone therapy (7) that may predispose to kidney disease:

• • Developing an abnormal level of cholesterol and other lipids, which may increase cardiovascular risk (dyslipidaemia)
  • High blood pressure (hypertension)
  • Weight gain
  • Type 2 diabetes

So, to answer the chief question that we asked in the beginning, yes, some aspects of gender affirmative treatments may predispose an individual to chronic kidney disease & subsequent kidney failure.

This article attempted to help you understand why & how this happens to allow you to:

Stay aware

Make relevant informed choices

Remain vigilant after the necessary procedures regarding potential kidney harming complications

IS THERE ANY HURDLE WITH DELIVERING OPTIMUM CLINICAL CARE TO TRANS PEOPLE WITH KIDNEY DISEASE?

At this point, it is imperative that we reveal another important pitfall in clinical care in nephrology with regards to kidney disease in transgender individuals.

Normally, doctors monitor the extent of kidney damage in all patients with chronic kidney disease with what we call the Estimated GFR or eGFR. This is calculated as a mathematical formula.

The eGFR formula is yet to be updated with necessary research evidence for use in transgender individuals. It still works with binary sexes – male and female. So, there is little scope for accommodating the myriad physiological variations & pathological manifestations w.r.t. kidneys that can surface from gender-fluidity.

This effectively leaves the doctor with lack of clarity on a good clinical tool to monitor kidney health in transgender patients. As a consequence, adequate monitoring via eGFR formulae may not be possible in trans individuals.

This ceetainly calls for more research focus on this area of transgender medicine and ensure adequate inclusivity.

BEST PRACTICES TO KEEP KIDNEY DISEASE AT BAY AFTER GENDER AFFIRMATIVE TREATMENTS:

Seek gender affirmation treatment from a valid, properly certified professional team trained in Transgender Medicine and necessary Reconstructive surgery.

Inform yourself thoroughly of potential complications from the gender affirming treatments you plan to undergo and how best to avoid them.

Stick to your prescribed dosage for hormonal supplements as decided by your medical team.

Try not to let the urgency to attain gender congruence to make you go overboard with hormonal supplements. It must be gradual and continue for the appropriate duration under due medical supervision.

Stay vigilant about any complications that you may develop after the reconstructive surgery or from hormonal supplements. If you do, report to your medical team without delay.

REFERENCES

1. Gender Affirmation Surgery https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6626307
2. Urethral Stricture after Phalloplasty in Transgender Women https://www.sciencedirect.com/science/article/pii/S1682606X13000777
3. Urethral Stricture after Phalloplasty in Transgender Men https://www.kidneynews.org/kidney-news/features/cardiovascular-and-chronic-kidney-diseases-impact-of-sex-and-gender-compounding-underdiagnosis
4. Effect of Sex Hormones on Cardiovascular Health https://www.acc.org/latest-in-cardiology/journal-scans/2018/06/01/11/55/endogenous-sex-hormones-and-incident-cvd
5. Effect of Hormone Therapy on pre-existing heart and kidney disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5720528/
6. Risks of Feminizing Hormone Therapy    https://www.mayoclinic.org/tests-procedures/feminizing-hormone-therapy/about/pac-20385096
7. Risks of Testosterone Hormone Therapy   https://www.mayoclinic.org/tests-procedures/masculinizing-hormone-therapy/about/pac-20385099