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The Role of Testosterone in Hypogonadism

Author Olivia Reid covers The Role of Testosterone in Hypogonadism on BackTable Urology

Olivia Reid • Jan 3, 2024 • 31 hits

Urologists Jose Silva and Mohit Khera speak on the nuanced role of testosterone in both the understanding and diagnosis of hypogonadism in male patients. Dr. Khera challenges the notion of using only one value for diagnosis, emphasizing the need to align symptoms like low energy, libido issues, and erectile dysfunction with the measured total testosterone.

Additionally, the misconception that aging alone causes testosterone decline is debunked with the studied impacts of comorbidities like diabetes, metabolic syndrome, obesity, stress, sleep deprivation, and shift work on testosterone levels. Lifestyle changes can have as great of an impact on testosterone levels as supplementation or treatment, given the bi-directional relationship between weight loss and testosterone levels. A comprehensive panel encompassing various hormone markers, vitamin levels, and testosterone levels, alongside symptom interpretation, are taken to yield a hypogonadism diagnosis.

This article features excerpts from the BackTable Urology Podcast. We’ve provided the highlight reel in this article, and you can listen to the full podcast below.

The BackTable Urology Brief

• Symptoms of hypogonadism include low energy, libido issues, erectile dysfunction, increased fat, and decreased muscle mass and require alignment with low testosterone (below 300 nanograms per deciliter) for diagnosis.

• Testosterone originates from cholesterol, with 90% from testicles and 10% from adrenal glands, and its breakdown leads to estradiol and dihydrotestosterone production.

• Lifestyle factors including diet, exercise, sleep, and stress reduction have been seen to impact testosterone levels.

• Lab evaluation for hypogonadism includes a measurement of total and free testosterone, LH, FSH, prolactin, estradiol, DHT, TSH, IGF-1, vitamin D, and B12.

• Poor sleep quality, instead of low testosterone levels, is often the primary cause of symptoms of fatigue, necessitating the importance of effective sleep patterns.

The Role of Testosterone in Hypogonadism

Table of Contents

(1) Hypogonadism Symptoms, Diagnostics & Misconceptions

(2) The Testosterone Pathway & The Impact of Lifestyle

(3) Diagnostic Approach to Hypogonadism: Essential Lab Markers

Hypogonadism Symptoms, Diagnostics & Misconceptions

Hypogonadism, clinically defined as a serum testosterone level below 300 nanograms per deciliter, presents a diagnostic challenge due to its symptomatic variability. Dr. Mohit Khera explains the drawbacks of using a specific testosterone level value as the sole criterion, stating the necessity of aligning symptoms with lowered testosterone levels for an accurate diagnosis. The most common symptoms expressed by male patients with hypogonadism include low energy, libido issues, erectile dysfunction, increased fat deposition, and decreased muscle mass.

In fact, there are many cases in which patients come in with testosterone levels above 300 yet still exhibit significant symptoms, necessitating treatment despite the laboratory readings. Oftentimes, patients attribute symptoms of hypogonadism with the natural process of aging which leads to underdiagnosis and undertreatment of the condition. Additionally, both patients and physicians often hesitate to broach the topic of sexual dysfunction, resulting in the silent suffering and missed opportunities for treatment in this patient population.

[Dr. Jose Silva]
Today, we're going to talk mainly about testosterone: low testosterone, hypogonadism, the pathophysiology of those patients, and what to look for when we're seeing those patients in the office. Mo, can you define hypogonadism?

[Dr. Mohit Khera]
Yes. Hypogonadism essentially means a man having a low serum testosterone value. The number you want to remember that we use is 300 nanograms per deciliter. I have a little problem using that number. I think that it's not really fair that we pick one number for everyone in the world, and if you're below that number, you feel bad and above that number, you feel good, but the number we use is 300. We were involved in some international guidelines that pushed that number to 350 and we can get into that. If a man has a low testosterone and he has signs and symptoms of low testosterone, then that patient suffers from hypogonadism.

[Dr. Jose Silva]
Not just only the patient with testosterone less than 300, do you need the symptoms also?

[Dr. Mohit Khera]
You bring up a very good point. Listen, so I have many patients that come in, and let's talk about the symptoms: low energy, low libido, erectile dysfunction, decreased muscle mass, increased fat deposition, some depression, and poor sleep. These are very common symptoms in men who have low testosterone. The most sensitive specific symptoms are the sexual symptoms, meaning libido and erectile dysfunction. If a man comes in with a testosterone level of 450 and he has every sign and symptom of low testosterone, you cannot treat him, because he doesn't have the testosterone value. Conversely, if he comes in with a level of 250 and says, "I feel great," I wouldn't treat him either. He really has to have both signs and symptoms and a low serum testosterone value.

[Dr. Jose Silva]
You mentioned that patient with increased adipose tissue. I have seen in my practice that sometimes some people are used to low testosterone and they don't know it versus the patient that has that decrease in the past six months and they will see it. Are you seeing those patients that have just constant low T and they just ride life, because that's what they know?

[Dr. Mohit Khera]
Yes. If you think about the symptoms I mentioned, low energy, low libido, ED, increased fat, decreased muscle, many men say, "I'm just getting older, right? This is just part of aging”. The reality is they don't realize that they suffer from a condition that can be treated and help to reverse many of these signs and symptoms. You're absolutely right. I think many people just accept it without getting tested to see if there's a potential treatment option.

[Dr. Jose Silva]
I'm sure you see it in your office also. Sometimes the wife is actually the one bringing the husband in saying, "Hey, I have seen it," and the husband either doesn't want to talk about it or, like you mentioned, they think that it's normal with age. Most of the time I think they're just embarrassed.

[Dr. Mohit Khera]
Yes. I talk about this, many times I call it suffering in silence. I know we're talking about testosterone, but when you talk about ED, erectile dysfunction, Peyronie's, low testosterone, many men are truly embarrassed to talk about sexual dysfunction and their symptoms. We know that the majority of men do suffer, and will suffer in silence. They think there's no treatment option or that their primary care doctor won't take them seriously. I'll tell you, my wife is a family practitioner. I said to her, do you screen for ED and low testosterone? She says, "To be honest with you, I have to go through diabetes, hypertension, sleep apnea. My patients are very sick. It's hard to get through everything in a short period of time." I think a lot of physicians don't go through when it gets to sexual dysfunction, don't get to sexual dysfunction on the chain.

[Dr. Jose Silva]
Just like you mentioned, I always ask the patient, "Hey, are you having low libido?" Because like you mentioned, most of the patients are just suffering in silence and they come because of BPH, even a kidney stone. When you start asking the patient, “hey, yes, I think”, or sometimes even in the office, they can see an ad for testosterone and they can see the symptoms, they can read it and say, "Hey, doctor, I think I have low testosterone."

[Dr. Mohit Khera]
Many times patients are almost relieved that you asked them. If you just say, "Mr. Smith, do you suffer from rectal dysfunction?" They will say, "Actually, I do." It's almost like, there’s finally someone asking me. "Tell me about your libido," which is not commonly asked. Now, conversely, many patients do come in specifically for those symptoms. They say, "Look, I got ED," or, "I have low libido." I would tell you that many men just suffer from silence when they really don't have to.

Listen to the Full Podcast

Testosterone & Hypogonadism: A Clinical Perspective with Dr. Mohit Khera on the BackTable Urology Podcast)
Ep 124 Testosterone & Hypogonadism: A Clinical Perspective with Dr. Mohit Khera
00:00 / 01:04

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The Testosterone Pathway & The Impact of Lifestyle

In the male body, testosterone originates from cholesterol, with 90% produced in the testicles and the remaining 10% from the adrenal glands. Testosterone is broken down into estradiol and dihydrotestosterone, which plays a role in conditions like gynecomastia, benign prostatic hyperplasia (BPH), and hair loss. Contrary to previous beliefs of andropause being solely age-related, the decline in testosterone can be primarily attributed to comorbid conditions like diabetes, metabolic syndrome, and obesity, rather than aging alone. Additionally, stress, sleep deprivation, and shift work can significantly impact testosterone levels.

Dr. Khera asserts that the four pillars to focus on when attempting to change testosterone levels via lifestyle changes include stress, sleep, diet, and exercise. This is due to the findings that sleep deprivation causes a rapid decline in serum testosterone levels, whereas weight loss, through diet and exercise, often leads to a substantial increase in the testosterone produced in the body.

[Dr. Jose Silva]
Going back to those symptoms or prior to that, in terms of the testosterone pathway, can you just give us a review of how testosterone works in the body?

[Dr. Mohit Khera]
Yes. Remember that testosterone comes from cholesterol. That's the basic building block for testosterone. Remember that the majority of testosterone in men comes from the testicles. Roughly 90% will come from the testicles. Roughly 10% will come from the adrenal glands. As men get older, there is a slight decline in testosterone production from the testicles. Then testosterone, remember, is broken down into two very important things. 0.3% of testosterone is broken down into estradiol. That's why you can get gynecomastia. Then 6% to 8% is broken down into dihydrotestosterone, which has been implicated for BPH and hair loss. It's very important to know the breakdown, because many times, patients will get anastrozole when they get testosterone. They'll give them finasteride. They'll give them medications to block the conversion. That is the essential pathway for testosterone.

Remember that testosterone, when I first started my practice, I thought that there was this thing called andropause, meaning that if you get older, men's testosterone goes down, because they're just getting older and they're going to suffer from low testosterone. Now, we know that's not true. Andropause is really not a true entity. Men who are very healthy do not see a significant decline in their total testosterone levels as they get older. It is the acquisition of comorbid conditions, diabetes, metabolic syndrome, obesity, and obesity is one of the notorious, that drops their testosterone as they age. Getting these comorbid conditions drops it. It's not aging in itself. Now aging does do one thing that's important, and we'll get into this, is that aging does increase SHBG. As the SHBG goes up, your free testosterone will go down as you get older, but we don't see significant declines in total testosterone in healthy men.

[Dr. Jose Silva]
So, do you see patients that are completely healthy that have low testosterone?

[Dr. Mohit Khera]
I do, but remember, there are many other factors that can drop their T, right? For example, stress and sleep. If you sleep deprived someone, five nights in a row, you can see a 15% decline right off the bat in their serum testosterone levels. That's important. There are many things that can drop their T: injury, traumatic brain injury. There's a lot of things you can see in healthy people that can still go down, but the majority, over 65%, of hypogonadism fell into three buckets. There was a wonderful study by Dr. Corona, came out of Italy. If it was secondary hypogonadism, it was obesity, metabolic syndrome, or diabetes, that’s 65% right there.

[Dr. Jose Silva]
You mentioned sleep deprivation. What about patients, and I always find these patients very hard to treat, patients that work at night?

[Dr. Mohit Khera]
Yes, it's difficult. It's very difficult, because the shift workers tend to have lower serum testosterone values, because of this fragmented sleep, but it's a risk factor. Now, it's not the whole thing. Sleep is just, I tell the patient, it's a pie. Sleep is a part of the pie, it's not everything. The four pillars I tell everyone they have to focus on are diet, exercise, sleep, and stress reduction. Again, it's diet, exercise, sleep, and stress reduction. I don't have a pill on the planet stronger than diet, exercise, sleep, and stress reduction. That can help with many things. Just forget testosterone. Diabetes, hypertension, joint pain, depression. I can go on and on. I tell patients, 50% of this is you helping me with diet, exercise, sleep, and stress reduction. I'll manage the hormones. Together, this team approach is very effective. Just giving someone testosterone and they keep not exercising, eating terribly, smoking, doesn't help as much.

[Dr. Jose Silva]
That's a fair point, a good point, actually. I always tell a patient, "Hey, you need to do it yourself also. This will help you." For example, the patient tells me, "I don't even have energy to do exercise." This might give you some, but you need to start doing it. You cannot expect everything to be done from testosterone.

[Dr. Mohit Khera]
Yes. What I've been focusing on and paying a lot of attention to lately is weight loss. Weight loss has this very strong bi-directional relationship with testosterone. There was a great study called the European Male Aging Study. What they showed was that if you lost 10% of your body weight, you can see almost 100 nanograms per deciliter increase in serum testosterone. If you lose 15% of your body weight, you can get almost 250 nanograms per deciliter increase in your serum testosterone. The converse is true. If you gain weight, you'll see a decline as well in testosterone. The best studies are with the bariatric surgery literature. When patients do bariatric surgery, they typically can see almost 250-300 nanogram per deciliter increase in their serum testosterone. I do feel that patients who lose weight not only benefit from an increase in natural testosterone, weight loss actually helps with a lot of the symptoms that we see with hypogonadism, meaning energy. Energy being the most. You tell someone to lose 15, 20, 30 pounds, their energy level goes up. They sleep better. We focus really heavily on weight loss.

Diagnostic Approach to Hypogonadism: Essential Lab Markers

When evaluating a patient presenting with symptoms of low testosterone, Dr. Khera outlines checking total testosterone first, followed by free testosterone. Free testosterone can be calculated using an online calculator which takes into account both total testosterone and SHBG. This additional calculation is vital, as free testosterone is the most sensitive indicator of symptoms. Next, for a comprehensive assessment, LH, FSH, prolactin, estradiol, DHT, TSH, IGF-1, vitamin D, and B12 are measured. Vitamin D and B12 supplementation can be used to address deficiencies, aiding in both immunity and potentially increasing testosterone production. Prior to beginning testosterone therapy, Dr. Khera stresses the importance of evaluating PSA and hematocrit levels due to the potential risks of erythrocytosis.

[Dr. Jose Silva]
You have that patient tell you, "Dr. Khera, I have symptoms of low T." What's the next step? What labs do you order?

[Dr. Mohit Khera]
Sure. Typically we'll check a testosterone, and I do check a free testosterone initially. The guidelines will say, just check a total testosterone. If the total testosterone is low, then you're supposed to repeat the total testosterone and check other labs, meaning LH, FSH, prolactin. I'm at an academic institution, so I do like to check other parameters like estradiol and DHT. Those are my go-to. Then how do you know if it's really due to low testosterone? Maybe he has hypothyroid. Maybe there's other things going on. I do check TSH, and we do use peptides a lot, so I'll check an IGF-1 to check the growth hormone level as well. Then I always check vitamin D and a B12 just to make sure that they're in check as well. Those are my go-to labs when I know that someone is hypogonadal. I will check a PSA and a hematocrit, because if I'm going to start them on testosterone, I gotta make sure the PSA's okay. I want to make sure they don't have a baseline elevation of erythrocytosis before I start them on it. Because again, erythrocytosis can be an issue.

[Dr. Jose Silva]
You mentioned vitamin D and I, we always talk, I'm in Florida, a lot of sun. We always were taught in medical school that vitamin D, sun exposure. I see a lot of workers that, they're always outside and I see a lot of patients with low vitamin D. Do you replace them, if you see a patient with a vitamin D?

[Dr. Mohit Khera]
Yes, I do. I think that there's several reasons. It helps with immunity. It helps with the testosterone production, endogenous testosterone production as well. If the levels are low, but sometimes people just don't absorb, you'll start at 1,000 units a day, 2,000, you have to go to 5,000, 10,000. Then eventually, you just may use the prescription version, which is 50,000 once a week just to get the levels up. I do think it's important. I do like vitamin B12. I think it can be helpful as well when people are talking about fatigue. Those are the ones I check, but I still go back to, I say, "Look, if you're really tired, the number one cause of fatigue is not low testosterone." The number one reason for fatigue is poor sleep. It's not the amount of hours that you're sleeping. It's how efficient you're sleeping as well. For example, Jose, if you went to bed last night and you slept eight hours, but you were only 30% efficient and I went to bed last night and I only slept five hours, but I was 80% efficient. I will feel better, the efficiency. It's really important that people get sleep. It's not just the amount of hours they're sleeping there. Sleep is very important. Number one, I say, I can give you all the testosterone you want, but if you don't sleep, you will be tired. There's nothing I can do about it. You have to sleep. If you want to sleep better, control your sugars, don't eat three hours before you go to bed, work out for me, manage your stress. It all comes together. Each one of those four pillars play off each other.

Podcast Contributors

Dr. Mohit Khera discusses Testosterone & Hypogonadism: A Clinical Perspective on the BackTable 124 Podcast

Dr. Mohit Khera

Dr. Mohit Khera is a professor of urology at Baylor College of Medicine in Houston, Texas.

Dr. Jose Silva discusses Testosterone & Hypogonadism: A Clinical Perspective on the BackTable 124 Podcast

Dr. Jose Silva

Dr. Jose Silva is a board certified urologist practicing in Central Florida.

Cite This Podcast

BackTable, LLC (Producer). (2023, October 4). Ep. 124 – Testosterone & Hypogonadism: A Clinical Perspective [Audio podcast]. Retrieved from

Disclaimer: The Materials available on are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.



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