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  • Writer's pictureJames W

hormones and mental health

I talk about hormone replacement therapy for men and women, how it is under-addressed in mental health, and why you should consider inquiring with your doctor. I preface with an experience with an MTF (male to female) therapy patient, since it relates to the discussion of hormones. I discuss male hormones in depth here.

Hormones are essentially genderized "Sex Steroids" that act like a messenger molecule throughout the body. (Yes I know genderized is not a word) Left unbalanced, your testosterone receptors are left high and dry.


MTF Therapy Patient

I moonlighted at a compounding Pharmacy located in San Francisco Bay Area. Things to know are how to make fentanyl lollipops, custom made tablets or capsules, suppositories for pets, palatable and tasty medication treats for dogs and the such. While compounding creams, lotions and ointment is nothing new, I admit I have never encountered a trans patient until this experience.

Typically, most Pharmacies software systems flag hormones if not proper for the gender. It almost always requires a manual override in the system and billing side. It is tedious to do, but not impossible. Most pharmacy software systems do not have a way of flagging transgender as a separate sex other than Male or Female. Also to consider is the central database of the PBM (pharmacy benefit manager) which requires patient information to be updated; this has to be done by the patient and requires him/her to call in.

What seemed unusual to me was creating an estrogen cream and non-commercially available estrogen/progesterone strength tablet(s) for an individual with a male name. I thought to myself, at first, that this did not seem right. In my prior experiences, I have never worked with trans patients before so this was new to me. I called the patient over the phone and received a rude awakening.

"Hi is this ______? This is James, Pharmacist over at ______________. I noticed we were compounding an estrogen cream which is usually given to female patients. Does this seem right to you?" What followed was an earful of colorful dialogue which I can't type out. To say the least, it was an eye opening exposure - for me. I wasn't trying to come off as an asshole but how was I supposed to know? This is not something I was exposed to during clinicals, residency or my academia. At times, providers do not meet face to face with the patient since they are handing the operational side of the business. While I am sure the Pharmacist handling the consult and clinical side of things understood the situation, I did not.


I admit, that I was not really sure how to approach this topic. I understood, like any normal human being, that this is a potentially sensitive topic. I wanted to learn a little bit more so I could provider better care in the future for similar patients. To preface, I did not have a trans friend before so it was difficult for me to relate, sympathize or understand. I did end up compounding the requested medications and later left that moonlight with some curiosity on how to be more sensitive to the needs of the trans community.

In my discovery, I found out that LGBTQIA training is mandated by a few payors now and it will definitely be a mandatory training component for health care providers in the future. While there is not a federal or state mandate for this training, it is a standard that some corporations are adopting. Interestingly enough, I did take the sensitivity training test and learned a lot.

I would later have a few MTF patients, in a skilled nursing setting. Drawing upon my experience and curiosity, I helped advise the clinical team to make better decisions.

testosterone deficiency


Understanding Anatomy

While having a MTF patient was an extraordinary experience for me, I have provided pharma care for both genders having hormones in the lower therapeutic range.

As a cycle of aging, our organs start to diminish and we lose our teenage drive. While females bloom much earlier than males, both populations may experience a decrease in natural hormone production starting in the 30s. We will, with certainty, experience this in our lifetime as we age. An 80 Year Old is NOT going to have the same natural hormone production as a 20 Year Old.

Depending how old you are (yes you, reading this blog), we are definitely not at the pre-pubescent stages of life where our hormones would be raging. Yes, I know - high school with a crazy time for everyone.

Testosterone is typically associated with Males while Estrogen is associated with females. Albeit, both hormones are actually important to both genders and require a delicate balance. Both are synthesized by Cholesterol through various pathways so it is important to eat a healthy diet.

Decrease in natural hormone production can lead to the following issues: high blood pressure, weight gain, diabetes, decline in mental cognition (smooth brain), fatigue, dis-interest in sex or libido, arrest of hair/collagen/skin growth, decreased red blood cell production, decreased muscle mass and decreased bone density . In short, it sucks.

Male Anatomy

In males, testosterone is not produced by the balls or testicles. In fact, it is synthesized in the adrenal gland which sits above the top of both kidneys. It is the same with females, however, the ovaries do function in testosterone production as well.

While your glands will convert DHEA or DHEA-S to testosterone, these hormones circulate through blood and binds to testosterone receptors of your cells which leads to a wide array of effects. "Cascade" is probably the better word to use here.

Female Anatomy

Remember I said testosterone is produced by females? Well the adrenal glands AND ovaries play a function here.

Estrogen production first begins in a part of your brain called the hypothalamus. Through a release of FSH (follicle stimulating hormone) or LH (lutenizing hormones), these will trigger the develop of "sex steroids." This can be viewed as gasoline to your vehicle; you need gas in order to drive. In crypto, this would be akin to gas like gwei in Ethereum for a transaction fee. Yes both male and females go through this production route.

Treatment Options for Males

So knowing how hormones our produced and understanding that natural hormone production decreases over time, what can we do about it?

We would need to run a diagnostic which, as of this moment, is done through a blood draw. A theranos-like concept diagnostic unfortunately does not work here since you need a lot more blood to measure hormones. I am sure we will see this technology in the future, where less blood volume is needed.

You will want to inquire about ordering a "Hormone Panel." Additionally, you will want to have your thyroid checked as well. This is typically ordered with routine check ups however the Hormone Panel is not.

Measuring Testosterone is a crap shoot

Depending which laboratory you go to, they utilize different guidelines set to determine the normal range of Testosterone. The range is widely huge and inconsistent. If you recall from my discussion above, the guidelines used are applied across the board of all ages. It should really be broken down by age, but unfortunately it is not. Here are a few examples below of how the reference range differs from Quest and Lab Corps, two major companies that handle lab diagnostics across the United States.

You'll notice that the range is widely different for both Testosterone, Free and Testosterone, Total. That seems really strange considering that all other things reference ranges that are consistent across the medical field. (Potassium, Sodium, Blood Glucose, PSA, etc)

The reality is that is it very possible for males in their 20s can have the same Testosterone levels of an 80 y/o; this person can go years without understanding why they are tired, lethargic, unmotivated. Unfortunately, this is not commonly screened by providers. Does it make sense for a 40 Year Old to have 270 ng/dL of Testosterone? No. It does not.

Depending which individual, practice or insurance company you speak to, Testosterone will not be prescribed or covered by insurance unless Testosterone, Total is less than 100. (Not equal to, but LESS THAN).

Typically, testosterone can be supplemented exogenously (not from natural sources) via table or injection. There are pellets but those hurt a lot and I rarely seem them used. It eliminates the need for weekly injections and can be changed out every quarter of the year. However these pellets are really huge and they hurt, A LOT to be put in. Pellets can be viewed as a concentrated and slow release of medication in a carefully formulated ball that is slowly absorbed your cells.

It is really important to screen and monitor your testosterone levels as you age. For the reasons above stated, we look at treating depression and anxiety with SSRI's or other psych medications. In reality, it s entirely possibly, and needs to be considered, that one's testosterone level is subtherapeutic.

Testosterone comes in many different esthers which affect frequency of dosing, length of duration, half-life and other pharmacokinetics. It is relatively cheap to purchase. Dosing of Testosterone Cyp maxes out at 200mg weekly. Anything over 200mg is considered "steroid levels" or "blasting". Studies have shown that steroid levels can potentially damage organs such as the liver and kidney. This is nuanced but I have to state the risks of blasting. The risk of having low testosterone is far worse, in my medical opinion, than having high testosterone.

Testosterone treatment for the most part is done empirically. We treat the patient, not the number. If someone does not feel well mentally, we need to strongly consider measuring Testosterone and supplementing.

Clomid can be used a treatment option before testosterone. This is a fertility drug.

Roid Rage

Testosterone gets a bad rap since it is a schedule 3 controlled medication. We are led to believe that this drug can be abused or cause dependency. There is a huge myth of "roid rage" which I wish to debunk. The thought here is that Testosterone will cause roid rage. However, this is much more nuanced in discussion.

Roid rage is essentially hyper aggression or an outburst of anger or violence. There are mixed studies on this topic. However, it can be inferred from studies that doses that are supratherapeutic (beyond what is normally prescribed or given), that there is increased aggression.

I cite an article here titled "Anabolic androgenic steroids and violent offending: confounding by polysubstance abuse among 10,365 general population men" The purpose of this article was to determine if anabolic steroids play a role in violence. Ultimately 10,000 Swedish males that were incarcerated were much more likely to report using anabolic steroids versus non-convicted individuals. However, I point out that correlation does not mean causation.

The article later concludes:

Our results suggest that it was not lifetime steroid use per se, but rather co-occurring polysubstance abuse that most parsimoniously explains the relatively strong association of steroid use and interpersonal violence.

While there are limitations of this study such as self-reporting and disclosures, it is highly unlikely that proper dosing of Testosterone or Exogenous Anabolics lead to roid rage. It is entirely possible that substance abuse plays a larger factor in this study.

In 1993, body builder Gordon Kimbrough killed his girlfriend. He mounted roid rage as a defense, which failed. He would be convicted of first degree murder.

In this study, titled Increased aggressive responding in male volunteers following the administration of gradually increasing doses of testosterone cypionate , it was concluded that increasing doses of Test Cyp increase aggression response.

In short, we need to consider what dosing of Testosterone one will be on. Anything that is 200mg or more is considered "Anabolic" and the possibility of increased aggression is much more likely.

convicted of first degree murder, roid rage is a bad defense.

Hormone Replacement Therapy, proper usage

So hormones are lipophilic in nature. It is important to wear gloves and be sensitive to demographics of your household. If you're using a cream for estrogen, it would not be proper to handle food preparation for children without washing hands first.

In recent development, drugs that are on the NIOSH list, which is pretty much everything, potentially can affect anyone who touches it. Hormone tablets, while they seem innocuous, should be handled with gloves.

making capsules.

Hair Loss

Depending where you are in the metabolism pathway, Testosterone is broken down by 5 Alpha Reductase to create 5 Alpha- DHT. Further metabolism of 5 Alpha-DHT creates byproducts which affect the growth of hair. While most people are vain about their hair line, is it possible that exogenous tesosterone can lead to hair loss in the wrong places. (Yes, the hair on your head)

There are medications such as finasteride that be used to address this issue. I would not recommend taking oral tablets and using a topical shampoo formulation here. The systemic effects of finasteride suck.

Mental Health

So we have an understanding of how hormones work now. Did you know that Depression, Anxiety or other Mental Health issues can be caused by subtherapeutic levels of Testosterone or Estrogen? More than 16 million Americans suffer from depression. This isn't readily obvious but testosterone plays a major affect here.

We have testosterone receptors in the brain which plays a significant role.

We understand that low testosterone can change your mood and may lead to symptoms of depression and anxiety. This can be seen as mood swings, irritability, stress, anxiety, depression, and so on. These symptoms are lumped together as "andropause" which is male equivalent of menopause in women.

We know that testosterone plays a role with libido, sexual function, muscle mass development, erectile function and so on. Symptoms of low testosterone is emotionally distressing which can create a downward spiral.

If you are in constant fight or flight mode, your adrenal glands produce high levels of cortisol. Cortisol can suppress the development of testosterone; this may be reversible or may be irreversible. The later is more likely. It is important to manage stress but unfortunately Silicon Valley work culture is difficult to get a handle on.

In short, consider having testosterone levels measured as the years go. This is not standard practice with most providers. If you feel like you are having depression and anxiety, know that there are other treatment options than SSRIs that can be looked at.

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