Many transgender people are often worried about drug interactions when taking PrEP with their Gender-Affirming Hormone Therapy (GAHT). Drug interactions occur when two drugs affect each other's blood levels, increasing or decreasing their concentration and, thus, efficacy.
It can be concluded from multiple studies that PrEP does not seem to significantly affect the blood levels of feminizing hormone therapy in transgender women. However, some of the hormones used in the feminizing-hormone therapy regime seem to slightly lower the blood concentrations of Tenofovir, a drug used in the PrEP regime. However, this decrease in blood levels is not significant enough to cause a loss in efficacy – at least with the daily dose PrEP regime.
While this conclusion is drawn from the data collected in multiple studies, it is still inconclusive. The reason behind this inconclusiveness is that most of these studies analyzed Tenofovir levels in the blood. At the same time, the mucosal and intracellular levels of Tenofovir matter when it comes to the efficacy of the drug.
HOW DOES PrEP INTERACT WITH GENDER-AFFIRMING HORMONE THERAPY (GAHT)
A major study and one of the first studies regarding PrEP and GAHT drug interactions was the iFACT 1 study by the Red Cross HIV Clinic. The study reported in 2018 about the drug interactions between the drugs included in the PrEP regimen and the GAHT therapy. The study recruited 20 transgender women who were on the GAHT therapy, including both estradiol and cyproterone. The study followed these transgender women for seven weeks and concluded multiple confirming results.
The participant transgender women were on Gender-affirming Hormonal Therapy for three weeks, after which they were started on PrEP (Tenofovir/Emtricitabine). Their GAHT therapy was stopped after two weeks, and the participants continued taking PrEP. GAHT therapy was then initiated again three weeks later, and PrEP was continued as well.
After seven weeks, the study concluded that neither PrEP nor the GAHT therapy had significant effects on each other's blood levels. The study found that transgender women on the GAHT therapy and PrEP showed almost similar blood levels of drugs at week seven (at the end of the trial) as were measured at week 3 and week 5 individually. This result means that taking PrEP while on gender-affirmation hormone therapy did not seem to reduce blood levels on estradiol, which meant that transgender women could continue taking HIV-preventive medication while continuing their feminizing hormone therapy. However, medication like GAHT should be taken 4-6 hours apart from PrEP regimens to increase efficacy.
Regarding PrEP, the study found a 13% decrease in the participants' blood levels for these drugs. While technically a decrease in overall drug levels in the blood, the study concluded that this decrease was not significant enough. The resulting PrEP levels in the blood were still above the minimum levels required for optimum efficacy of the drugs.
Taking pre-exposure prophylactic treatment for HIV in the transgender community has always been a subject of confusion. Part of this confusion stems from a shocking lack of knowledge about PrEP in the transgender community, particularly among transgender women. Multiple studies have attributed misconceptions about PrEP as having adverse effects on GAHT to be the leading cause of low adherence with PrEP in transgender women.
Although personal concerns about PrEP in transgender women are a major factor, it is not the only one. Studies indicate that provider hesitancy and a general lack of promotional campaigns for PrEP among the transgender community also play a major role in the low utilization of prophylactic treatment among the transgender community. These factors took roots from a lack of supporting evidence that PrEP does not interact adversely with GAHT. Moreover, research into this issue wasn't always prioritized up until 2018.
FHT AND ON-DEMAND PrEP
Traditionally, PrEP forms part of a daily pill schedule that is taken for as long as protection from HIV is required. This can mean taking PrEP indefinitely. Although PrEP does not carry many side effects and the daily pill schedule is relatively easy to follow, taking a daily pill isn't exactly the easiest thing for many people. Most people worry about the side effects of taking a pill daily for the rest of their lives, which poses a problem. A shorter, much flexible schedule of PrEP exists, although it is not approved in the U.S.
On-demand PrEP is the short version of the traditional PrEP regimen that serves to protect against HIV.
Studies looking into the interactions between PrEP and FHT also look at the relationship between FHT and the on-demand schedule of PrEP.
These studies, however, found that when taking PrEP with FHT, the on-demand schedule does not build up enough concentrations of the drug in a person's blood to confer protection against HIV. Therefore, the current guidelines discourage using on-demand PrEP with FHT if adequate protection against HIV is required.
HOW DOES THE FEMINIZING HORMONE THERAPY WORK?
Feminizing Hormone Therapy, or FHT, works by bringing about changes in the body that are more consistent with the female gender. FHT is ideal for people with gender dysmorphia who don't identify with their gender at birth. FHT is also ideal for non-binary and intersex individuals.
Feminizing Hormone Therapy has three components:
- Anti-androgen therapy/androgen blockers
- Estrogen replacement
- And progesterone supplements
The anti-androgen component works by blocking the effects of testosterone, a hormone responsible for bringing changes in the body consistent with the male gender. These changes are necessary to bring about feminizing changes in the body. These changes include:
- Shrinking of testis
- Decrease in the overall muscle mass
- Thinning of facial and body hair
Estrogen and progesterone are given to bring about feminizing changes in the body. These changes include the development of breasts, increased fat deposition on buttocks and face, and softer skin – all of which are consistent with the female gender.
Feminizing Hormone Therapy can be used individually or in conjunction with gender reassignment surgeries to change the gender of a person effectively. This treatment is indicated for everyone who does not agree with their assigned gender and wants to change it to the feminine gender.
WHAT ARE THE SIDE EFFECTS OF FHT?
Like all medications, feminizing hormone therapy also carries some risks. The drugs in this therapy are off-label, meaning that the FDA does not indicate these drugs for this purpose. Therefore, most of the use-aspect of these drugs is directed by your physician's knowledge and experience.
The anti-androgen component of the therapy carries the following risks:
- Polyuria (increased urinary frequency)
- Polydipsia (increased thirst)
- Hypotension (reduction in blood pressure)
- Hyperkalemia (increased potassium in the blood, which causes arrhythmias)
- Fatigue & weakness
- Low bone density
Androgen blockers also make it difficult to assess prostate health. People who are assigned male at birth over 50 with a strong history of prostate cancer in their families should get annual prostate examinations when taking FHT.
Estrogen can cause all sorts of problems as well. Some of the side effects caused by estrogen are mild and go away on their own. Other side effects are much severe and require physician care. Some of the common side effects of estrogen include:
- Mood swings
- Mild to severe headaches
- Nausea and vomiting
Other complications that are not as common include:
- Deranged liver enzymes
- Formation of gallstones
- Development of diabetes
- Raised blood pressure
Estrogen can also increase the risk of occurrence of certain medical conditions. Therefore, a complete health checkup is required before this therapy is started. Your physician may ask you about your medical and surgical history and any positive family history that may be significant. Estrogen may not be right for you if you have a risk of any of these conditions:
- Breast cancer
- Diabetes mellitus
- Heart disease, such as valvular problems
- High blood cholesterol
- Kidney dysfunction
WHAT ARE THE SIDE EFFECTS OF PrEP?
PrEP is a treatment regimen that may carry some risks. Most of the side effects of PrEP are benign and disappear after some time without any medical intervention. Almost all of these side effects are experienced when PrEP is first started. These include:
- Decrease in appetite
- Weight changes
- Pain in abdomen
The side effects of PrEP can vary depending on your dose and the choice of drugs you're currently using. Some long-term complications might develop in a fraction of patients. The most dreaded long-term complication of PrEP is a damaged liver. There are multiple danger signs that you should keep an eye out for when taking PrEP. Consult your doctor immediately if you notice any yellowing of eyes, dark urine, decreased appetite, abdominal pain, or an irregular heartbeat.