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Dr Mariano, I was diagnosed three years ago with adult onset hypogonadism and have been on TRT for since then. I have been at the point, for some time, where all my hormone levels, are well balanced I feel strong, energetic, and have an excellent sense of well being, however, one of the main reasons I sought treatment was for loss of libido, and this issue continues to be a real problem.
Initially, upon starting TRT, my libido was terrific again, but only for about a month or so and then it diappeared. Without mentioning names, I have been, over the last three years, to three doctors, all of who are considered to be top experts in the field of TRT and still no answers. The last doctor stated that the reason I experienced the increase in libido initally was what he called ” the initial surge in dopomine” . However, none of the doctors have been able to develop a protocol that helps maintain that effect.
Last week I had a consult with another doctor with a practice on the west coast that specializes in hormone therapy and this particular doctor feels that the problem may be in the area of brain neurotransmitters. He has suggested treatment with Trazadone, which he incidentally cited several studies where it was used to treat libido problems, included an urologist who cured his own impotence problems back in the 80’s using trazadone. He also talked about the use of Selegiline.
I was wondering if you would be so kind as to comment on this train of thought and about his suggestion using trazadone and Selegiline.
Thank you.
@jay 338 wrote:
Dr Mariano, I was diagnosed three years ago with adult onset hypogonadism and have been on TRT for since then. I have been at the point, for some time, where all my hormone levels, are well balanced I feel strong, energetic, and have an excellent sense of well being, however, one of the main reasons I sought treatment was for loss of libido, and this issue continues to be a real problem.
Initially, upon starting TRT, my libido was terrific again, but only for about a month or so and then it diappeared. Without mentioning names, I have been, over the last three years, to three doctors, all of who are considered to be top experts in the field of TRT and still no answers. The last doctor stated that the reason I experienced the increase in libido initally was what he called ” the initial surge in dopomine” . However, none of the doctors have been able to develop a protocol that helps maintain that effect.
Last week I had a consult with another doctor with a practice on the west coast that specializes in hormone therapy and this particular doctor feels that the problem may be in the area of brain neurotransmitters. He has suggested treatment with Trazadone, which he incidentally cited several studies where it was used to treat libido problems, included an urologist who cured his own impotence problems back in the 80’s using trazadone. He also talked about the use of Selegiline.
I was wondering if you would be so kind as to comment on this train of thought and about his suggestion using trazadone and Selegiline.
Thank you.
Many men that come see me still lack libido despite testosterone replacement therapy.
The initial improvement in libido with testosterone replacement may be associated with supersensitivity to dopamine that occur with chronic lack of testosterone, which increases dopamine production. Dopamine is very fickle as a signal. Raising dopamine continuously reduces nervous system sensitivity to dopamine (by reduction in the number of dopamine receptors). This is called tolerance. Once tolerance occurs, then libido is reduced to a baseline. This baseline is determined by multiple factors, the same ones which determine libido.
Libido requires many factors to be optimized including:
- Testosterone needs to be optimized – a good target is at least 650 ng/ml. Supraphysiologic values can cause changes which may also reduce libido (e.g. excess estrogen, etc.).
- Estradiol increases sensitivity to testosterone. Too much estradiol will suppress libido – one reason is that estrogen acts like an Monoamine Oxidase Inhibitor, which raises serotonin significantly. Serotonin suppresses libido by reducing dopamine signaling activity. Too little estradiol will impair libido by making cells insensitive to testosterone. Estrogen, itself, is directly important for sexual aggression or drive. Male territorial sexual behavior is driven by estrogen.
- Thyroid hormone needs to be optimized. Exogenous testosterone replacement, itself, reduces thyroid hormone production by reducing testicular thyroid releasing hormone production. The rise in testosterone may lead to a rise in estradiol, which may reduce free thyroid hormone by increasing thyroid binding globulin production from the liver. This would then create a functional hypothyroid state, causing problems with energy and libido.
- Hypothalamic-pituitary-adrenal dysregulation needs to be addressed. Low cortisol production impairs energy production and increases stress. (I no longer like the term adrenal fatigue since it overly focuses on the adrenal glands when the cause is elsewhere). Low progesterone may lead to an increase in anxiety, stress. Low DHEA can also impair libido. Low pregnenolone may impair concentration for sex.
- Excessive nervous system norepinephrine signaling (which may be a compensation for low thyroid, low cortisol, low iron, etc. to generate energy or body heat) may cause a loss of dopamine signaling – reducing libido. Thus, excessive norepinephrine production and its causes need to be addressed. The loss of dopamine signaling may be addressed separately but it may not be sufficient to do so since excessive norepinephrine will outweigh dopamine (e.g. if a freight train was coming at you, you would hardly have libido nor an erection).
- Nutrition has to be optimized. Without necessary and optimized nutrient availability for neurotransmitter and hormone production and metabolism (such as Vitamin A, C, D, B12, B6, Folate, Iron, Selenium, etc. etc.), then improving signal activity – such as increasing testosterone – would have little effect since the cellular changes in metabolism triggered by the signal cannot be activated.
Thus, when it comes to libido, there is a huge area to examine to determine what other treatments are necessary to improve libido. It is not adding testosterone alone.
Trazodone is a medication I would never give to a man who is not hypogonadal and old. Good testosterone plus Trazodone has a high risk of priapism. With one of my patients, all it took was a single first dose of 25 mg of Trazodone from a primary care physician to cause priapism – a medical emergency where the penis can die from lack of blood flow. The emergency room tried epinephrine injections to the penis but it did not work. So surgery was performed. He was distraught and suicidal when he came to me. His penis ended up being purplish, discolored and in a weird twisted shape after surgery. Trazodone is like playing Russian Roulette with your penis. The younger a man, the higher the probability of priapism.
Selegiline is a monoamine oxidase inhibitor (MAOI). MAOI inhibitors primarily increase serotonin. But they can also increase dopamine and norepinephrine. At low doses, Selegiline can avoid the dietary requirements of other MAOIs and high dose Selegiline, which are necessary to avoid excessive blood pressure and a stroke or heart attack. Selegiline is used in the treatment of Parkinson’s Disease since it can increase dopamine signaling significantly. For libido, perhaps Selegiline can increase libido via increasing dopamine. The problem is that it also primarily increases serotonin, may reduce libido by reducing dopamine production. If norepinephrine signaling is excessive, then the increase in serotonin may just be enough to reduce norepinephrine and restore dopamine production lost because of norepinephrine production. Thus on balance, perhaps libido would be restored. However, there is also a significant chance, via the serotonin increase that libido itself would be reduced. Clinically, I find Selegiline’s serotonin increase outweighing the other signaling changes it causes. Thus on whole, it suppresses llibido. But given the possibility it may improve it, it may be worthwhile to give it a try. I would still recommend the dietary changes at least in consideration since the point where tyramine and other substance in the diet can cause a stroke varies with people, though at doses from 5 to 10 mg a day of Selegiline, it seems save to have a regular diet for most people.
Dr M. Thank you for your comprehensive response. may I ask, do you currently accept new patients, and if so, do you trat patients who are out of state?
Thank you.
Selegiline is a monoamine oxidase inhibitor (MAOI). MAOI inhibitors primarily increase serotonin. But they can also increase dopamine and norepinephrine. At low doses, Selegiline can avoid the dietary requirements of other MAOIs and high dose Selegiline, which are necessary to avoid excessive blood pressure and a stroke or heart attack. Selegiline is used in the treatment of Parkinson’s Disease since it can increase dopamine signaling significantly. For libido, perhaps Selegiline can increase libido via increasing dopamine. The problem is that it also primarily increases serotonin, may reduce libido by reducing dopamine production. If norepinephrine signaling is excessive, then the increase in serotonin may just be enough to reduce norepinephrine and restore dopamine production lost because of norepinephrine production. Thus on balance, perhaps libido would be restored. However, there is also a significant chance, via the serotonin increase that libido itself would be reduced. Clinically, I find Selegiline’s serotonin increase outweighing the other signaling changes it causes. Thus on whole, it suppresses llibido. But given the possibility it may improve it, it may be worthwhile to give it a try. I would still recommend the dietary changes at least in consideration since the point where tyramine and other substance in the diet can cause a stroke varies with people, though at doses from 5 to 10 mg a day of Selegiline, it seems save to have a regular diet for most people.
Given my 10 year history of poor to no libido, I decided on trying Deprenyl (Jumex) 4 years ago. After reading about it’s pharmacodynamic, I placed an order for Jumex. The literature says it’s a selective MAO-type B inhibitor >10 mg/day. I did bother about the dietary restrictions despite keeping far below the 10 mg/day dose.
On the first week I was on 2.5 mg twice a week (skipping days between doses). No improvement in libido was observed. Second week, same thing, and yet no improvement in libido whatsoever, although my focus and mood slightly improved. On the third week, I bumped up the dosage to 5 mg twice a week, still skipping days between doses. Still no libido improvement in sight. So I decided to quit taking it. The day after I went cold turkey, I inadvertently had a square of dark chocolate. 20 minutes thereafter, I started getting extrasystoles–I thought it was unrelated and went on reading the book I was reading at the time. But more of them came about, and my heart rate I could feel was going up. I went outside walking around my home thinking that it’d take my mind away from what I felt might be a self-feeding vicious circle of anxiety. However, my heart rate was going up more and more, that is, more BPM and pounding, so much so that I could feel my carotid arteries bouncing. I then started feeling nauseated. There, I picked up the phone, called up a nearby friend of mine telling him that I was driving to his place, for I wanted him to take me to the ER as I wasn’t doing well at all. When I reached his place, I felt awful and panicky quite a bit. I had never ever felt that bad ever and I really thought I was having a heart attack or that something terrible was taking place or going to take place.
Once in the ER, I had no choice but to tell the physician that it was because I took a course of Selegiline Hydrochloride. Clearly they did nothing but to keep me under observation for a while, and that’s ok. On admittance to the hospital my BP was 188 over 111 with a HR in the 130ies.
It turned out that what I had was a bad panic attack, which I initially thought was a hypertensive crisis. I had never ever even came close to experiencing such an event in my life. I had some anxiety just like everyone does, cause life just happens, but nothing of that kind. I had 5 more of those panic attacks until DPR cleared my system I guess, which IIRC has a long clearing time.
I haven’t had any other panic attack since.
Since DPR is known to be a sympathomimetic, and that dark chocolate contains both PEA and theobromine, I take it that they synergised to bring about excessive SNS activity. DPR if I recall correctly also potentiate PEA.
Moral of the story is : I’ve learned some lesson on that day.
Many have told me that DPR shouldn’t have produced such an adverse outcome given the low dose I was on. However, I’m already naturally stimulated, so DPR + dark chocolate likely only magnified what was already present.
I do not think I’ll ever go back on DPR.
trazadone (100mg before bed) did something weird with my sex drive. It increase my ability to have an erection, even firmer. But it inhibited my drive. I also had some painful erections, but never lasted too long to make me go to the ER (plus the thought of them stabbing a needle into my dick wasnt to appealing).
Dr Mariano:
What is your opinon of Dopamine agonist therapy for libido issues using such medications as Bupropion or pramipexole, of example.
My reason for asking is that I recently read an article by Dr. Irwin Goldstein, Clinical Professor of Surgery at University of California at San Diego and Director of San Diego Sexual Medicine where he maintains his clinical practice. Dr. Goldstein mentioned that often men who’s hormones are properly balanced still experience libido issues and he has found these medications to invalauble to his success in treatment.
Just interested in your thoughts. Thank you.
@DrMariano 342 wrote:
Exogenous testosterone replacement, itself, reduces thyroid hormone production by reducing testicular thyroid releasing hormone production.
Is it a significant part of the TRH produced by the whole body?
From wikipedia :
In addition to the brain, TRH can also be detected in other areas of the body including the gastrointestinal system and pancreatic islets.
I wonder how much is made outside the brain and in testicles specifically.
That in itself could be a good reason to always take hcg with TRT.
@gu3vara 1025 wrote:
Is it a significant part of the TRH produced by the whole body?
From wikipedia :
In addition to the brain, TRH can also be detected in other areas of the body including the gastrointestinal system and pancreatic islets.
I wonder how much is made outside the brain and in testicles specifically.
That in itself could be a good reason to always take hcg with TRT.
Yes, a significant amount of TRH is made by the body, outside of the hypothalamus. This includes other parts of the brain and the testes.
An alternative to doing HCG is to simply optimize thyroid hormone signaling, thus bypassing TRH, TSH, etc. HCG is in short supply and thus can’t always be relied upon in treatment.
Libido can be cure by taking medications and taking care of our selves. But for me I rather take medicines for I have my nightly work I’m always tired and have no time for sex. that’s why I took wyld natural, to gain extra energy and to raise my libido for I have my wife waiting for me at home. What is your pill? They say viagra is good but I don’t want to try it coz im really satisfied wyld gave to me plus it is safe rather than that coz this is herbal supplement.🙂
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