So we eventually end up doing everyday dosing because the whole point of HRT is to avoid
feeling like crap, right?
Welcome to the Hormones Happen podcast, a podcast designed for individuals like you
who are curious about the amazing benefits of hormonal placement therapy.
I'm your host Jeremiah and I'm a nurse practitioner who specializes in HRT.
I've seen firsthand the debilitating effects of hormone deficiency and have personally experienced
the benefits of optimization.
My goal is to arm you with information regarding the good, the bad, and even taboo aspects
of HRT while answering your burning questions.
Please join me for today's episode of the Hormones Happen podcast.
Welcome back to the Hormones Happen podcast.
Last time we talked about the amazing benefits of estradiol for both men and women and today
it'll be a very similar topic.
However, we're going to be talking about the redheaded stepchild of hormone replacement
therapy called progesterone.
Many people just like estradiol feel that this is a female only hormone.
However, there are a plethora of benefits for both men and women that all occur from
progesterone.
So without further ado, let's get into it.
Progesterone is a steroid hormone that is produced in the ovaries in women, the testes
in men, and the adrenal glands in both sexes.
It acts as a precursor to other vital hormones such as testosterone and cortisol.
It's primarily known for its effects on regulating the menstrual cycle, supporting pregnancy,
and balancing estrogen in women.
However, this hormone also supports testosterone production in men and prevents estrogen dominance.
Now, typically after the age of 30, progesterone levels slowly decline, leading to a plethora
of symptoms such as difficulty sleeping, mood swings, anxiety, weight gain, brain fog.
Is this starting to sound like low testosterone a little bit?
Perhaps.
A common scenario that I often see play out in my office is a woman between the ages of
30 and 50 coming to me with a main complaint of difficulty sleeping, irritability, and
just feeling anxious when she was never an anxious person before.
And when she does go to sleep, she has a hard time staying asleep, oftentimes waking up
with anxiety or even with cold sweats.
That's the main complaint.
The other complaint I often hear is a woman, same 30 to 50, will come in saying that she
eats healthy.
She exercises routinely, however, she just continues to have weight gain and just fat
accumulation, especially around the midsection.
Now, I don't only hear these complaints from a woman who's not on HRT, but if a woman has
had a hysterectomy in the past and is now on estradiol without progesterone, I oftentimes
hear the same exact complaints, sometimes to even a worse degree.
While I do hear these similar complaints in men, typically once we start testosterone,
they subside.
When a man starts TRT, this can increase the amount of progesterone that's produced in
the adrenal glands.
And although it doesn't appear that there's a large quantitative difference between progesterone
in men and women, it does appear that men are less sensitive to the outward effects
such as anxiety, insomnia, and weight gain.
I have, however, supplemented progesterone in men with a great effect on anxiety and
to help with sleep.
I personally take 200 to 300 milligrams of progesterone when I'm having a difficult time
sleeping and it honestly works miracles.
Let's talk about progesterone's role in weight management for a minute.
There are several mechanisms in which progesterone helps to control weight gain, such as regulating
cortisol, balancing estrogen, and supporting thyroid function.
Progesterone acts as a buffer to the stress hormone called cortisol.
And when progesterone levels are low, cortisol levels spike, leading to a fat storage predominantly
around the midsection or belly.
Now, although estradiol promotes fat loss, high levels can cause fluid retention and
progesterone helps to regulate this by decreasing bloating or swelling in the extremities.
And finally, progesterone has a reciprocal relationship with the thyroid by decreasing
thyroid binding globulin, increasing the activity of thyroid hormones, increasing synthesis
and metabolism of thyroid hormones, increasing conversion of T3 to T4, and up-regulating
thyroid peroxidase.
So basically, it helps to increase the amount of thyroid hormone while improving its efficiency.
Another physiological effect of progesterone, which I do feel contributes to weight loss,
specifically fat loss, is its ability to increase thermogenesis.
Progesterone does increase your basal temperature.
And I've noticed firsthand that if I take a progesterone and go to the gym the next
morning, I do sweat a lot more than if I had not taken the medication.
Some other amazing benefits of progesterone include a positive effect on bone health by
stimulating osteoblast activity, promoting brain and nerve repair, maintaining healthy
blood vessels, and reducing inflammation.
One of the most beneficial and quickly recognized effects of progesterone is the calming effect
that it has by increasing the production of GABA, which is a neurotransmitter that promotes
relaxation and well-being, leading to fillings of calmness and reduced anxiety.
I do want to further elaborate on some of the anti-anxiety and calming effects of progesterone,
as this is one of the most beneficial aspects for both men and women.
Now, the interaction between progesterone and gamma-aminobutyric acid, or GABA, receptors
is truly amazing.
GABA receptors are a key component of the brain's inhibitory system, and are responsible
for the calming effects that promote relaxation, and they act as almost a brake on an overstimulated
mind.
When there's not enough stimulation of the GABA receptors, the brain experiences symptoms
such as increased neuronal activity, leading to symptoms like anxiety, nervousness, difficulty
relaxing, mood swings, trouble sleeping, and in very severe cases, seizures.
When progesterone is metabolized, one of its primary metabolites, allopregninalone, acts
as a powerful modulator of GABA, amplifying its brake-like effects on the brain.
It's been known colloquially as the valium of the brain for this reason.
Oftentimes when I follow up with a woman or man who's recently started HRT or TRT and
I've used progesterone, they'll describe the sensation as almost turning down the volume
on a noisy or chaotic mind.
Now it is used less often in men, but typically if a man is on TRT and they're still having
a lot of anxiety, progesterone is a very useful tool in your toolkit to help to combat that.
Now like I've said, I've taken progesterone and I still do, and I can attest to the fact
that it helps you sleep, but it also helps produce a sense of calmness the next day.
And it varies from person to person, but progesterone's amazing effects on essentially sensitizing
the GABA receptor is paramount.
Key effects of progesterone, allopregninalone, and GABA receptor activity result in anxiety
reduction, better sleep, mood stabilization, and neuroprotection.
Now let's go one step further into the neuroprotective or brain protective properties of progesterone.
I try to keep this podcast more conversational and less academic, but to really emphasize
the benefits of brain health and progesterone, we really do need to dive a little bit deeper.
So stay with me on this.
Research has shown that progesterone exerts neuroprotective effects, offering hope for
better outcomes in cases of traumatic brain injury, stroke, and even neurodegenerative
diseases, but how does it do this?
The powerful anti-inflammatory effects of progesterone help to reduce damage, promote
repair, and enhance recovery after an injury to the brain, but it also helps to stabilize
the blood-brain barrier, which is a critical structure that protects the brain from harmful
substances after injury.
Additionally, it helps restore the protective sheath around neurons, preserving their functionality
and enhancing brain recovery while mitigating apoptosis, which is a medical term for the
natural process that removes damaged or unneeded cells from the body.
And lastly, progesterone stimulates the growth of new neural connections in the process called
neurogenesis, which is essentially rebuilding the brain's neural network after an injury.
Now that we've talked about the importance of progesterone for both men and women and
the issues associated with low levels, what options do we have regarding replacement?
Now progesterone, much like testosterone and estradiol, comes in a variety of forms, including
oral, transdermal, pellets, patches, and probably some that I'm not even aware of.
I will tell you the most common variations are pills and creams.
From the research available today, I always recommend as first line an oral micronized
progesterone because of the conversion to allopregnanolone when it's metabolized by
the liver.
Now there are some women who are overly sensitive, and probably men too, I just haven't experienced
it, who are overly sensitive to the effects of allopregnanolone.
And despite decreasing the dosage, they just report feeling drowsy the next day.
And so for these individuals, cream is a great option because at the end of the day, the
main benefit to the progesterone and the most important aspect is basically antagonizing
the effects of estradiol to prevent uterine lining thickening while you're on HRT.
Now with the cream, you will not get the same neurocognitive benefits as far as the anti-anxiety
or the increased sleep effects, but you're still getting the most important aspects,
which is preventing negative complications of HRT.
Now I've seen quite a bit of variance as far as the studies and expert opinion regarding
the oral versus the creams of progesterone, but one concern with the creams is that progesterone
is a larger molecule size and there's concerns that it may not be adequately absorbed into
the capillaries causing less protection against estrogen.
I have heard several experts dispute this claim and report that while on progesterone
cream checking levels is trickier because it tends to under sense on blood work and
over sense on saliva testing.
So it's really difficult to say, does the cream protect the uterus as much as the oral
virgin?
And it's really impossible for us to know because I do not think there have been any
significant studies where they've done, you know, uterine lining biopsies or specific
ultrasound imaging to really assess it.
But at the end of the day, these are all calculated risks that we have to take and we have to
consider.
And so my first line is the oral.
Second line would be the creams from me.
Now this is not medical advice.
This is just how I run my practice.
How much to give and when to give it are also highly controversial due to the variabilities
and thought processes among experts and the lack of study designs used for this specific
population.
Now regarding dosage, this varies anywhere from 50 to 400 milligrams.
I will start my patients off at 200 milligrams, which appears to be a great dosage to help
with anxiety reduction and promoting sleep.
Now that's not to say that I haven't had to make dosage adjustments, either decreasing
it or increasing it from there.
But 200 just seems to be a great middle of the road starting point from my experience.
Some experts believe you should mimic a natural menstrual cycle and use the progesterone for
14 days at the beginning of the month, then refrain from use for the rest of the month.
Whereas some say use every other day or every day.
Now my biggest issue with the 14 day on 14 day off approach is that the 14 days that
you're taking it, you feel great.
You're sleeping great.
Your anxiety is controllable.
But the 14 days that you're not taking it, you feel horrible, maybe even worse.
So from my personal opinion, I do not see the point in not treating those symptoms that
you're coming to me to treat.
The reason that the 14 day on 14 day off and every other day frequencies exist is because
there is some speculation that the progesterone receptor can be down regulated with everyday
use causing like a desensitization effect in addition to down regulating the estradiol
receptor.
Now, while it will down regulate the estradiol receptor, I haven't seen any research or scientific
studies that do show that everyday use will down regulate the progesterone receptor needing
you to increase your dosage to get the same effect.
I typically start most of my patients on every other day dosing, but oftentimes what I hear
is that on the days they don't take it, they feel like crap.
So we eventually end up doing everyday dosing because the whole point of HRT is to avoid
feeling like crap, right?
I have seen in a couple cases that the progesterone will decrease the estradiol levels, but this
is an easy fix while on estradiol replacement.
We just increase the dosage.
So as you can see, there are several different ideologies regarding how, how much, and when
to take progesterone.
Remember when I said the world of hormone replacement therapy was still the Wild West?
This is exactly what I was talking about.
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All right guys, let's get into some Q&A's here.
I have a couple questions.
Can TRT be injected like insulin?
Well, this is a great question.
I am assuming he just means subcutaneously.
So the answer is absolutely.
Now subcutaneously just means the fat tissue, whereas intramuscular is just into the muscle.
Now there are a couple variables you want to take into account here.
One of them being the carrier oil that's mixed with testosterone.
Now testosterone is hydrophobic, meaning that it hates water.
So it has to be mixed with some type of oil.
There are some oils that are more inflammatory than others.
For example, grapeseed oil and cottonseed oil.
These are the ones you would typically get.
Let's say Walgreens, CVS.
Whereas grapeseed oil, which is the oil that I personally use for all of my testosterone
products is not as viscous or thick and it's also not as inflammatory.
The other thing you want to take into account is the size of the needle.
Traditionally needles as big as 23 to 25 gauge, one and a half inches were used to inject
deep intramuscular.
For subcutaneous or even shallow intramuscular, we use, well, insulin needles, 27 gauge half
inch needles.
These are small enough to be able to inject the fat, but big enough to be able to inject
the muscle without really worrying about hitting any major blood vessels.
Definitely not the bone.
And it gives you a lot of freedom as to where you want to inject.
Now the biggest difference between subcutaneous and intramuscular injection is the absorption
times because there's greater vascular supply to the muscle.
So if you inject it into the muscle, it's going to absorb more quickly, which is not
really a big deal if you're injecting it at least twice a week.
If you're doing it only once a week, which I don't recommend, then subcutaneous may be
a better option for you just because it's going to be more of a slower absorption rate.
And the one other caveat to subcutaneous is that when you do inject it, you're going to
develop a little bit of a nodule, which is the oil depot.
And if you rub it, it'll usually just dissipate a little bit, but it can be a little irritating
for most.
I've done both subcutaneous and intramuscular.
I much prefer intramuscular.
I just feel that it gives me better symptom relief and better effect.
Why is my testosterone level lower?
First question, I am a 38 year old male on TRT and my doctor has me on 200 mg every two
weeks.
When I started the shots, my testosterone level was 214, but when I recently got my
levels checked, it was 60.
I feel good a couple of days after my injection, but feel worse than before treatment the week
leading up to my next shot.
This is more common than you guys think.
However, it's been a minute since I've seen dosing every two weeks.
As a little background here, when you take an exogenous form of testosterone, whether
that be injections, creams, or pills, your endogenous or natural production stops because
your brain doesn't know you're now getting testosterone from a needle and it thinks that
it's making too much.
So it stops its natural production, which is called shutdown.
Now, assuming he's using testosterone cypionate, that means he's getting a peak effect of the
medication in about three to four days and half the medication is out of his system in
a week.
We call this a half life.
Now, going one week further means that he's essentially getting half of the half out of
his system.
So from the initial 200 mg, he's really only working with about 50 mg, but there are a
lot of variables to this and I'm just making a broad assumption based off normal half-lives
of medication here.
So remember, the natural production of testosterone is still shut down, but now as the exogenous
levels fall, you actually dip below your starting testosterone level.
Now, if you were to stay off of it, your natural production would start again, but in that
two week window, you're pretty vulnerable.
So as I've said before, I recommend at least twice weekly injections to avoid this issue.
All right, this last question hits pretty close to home as far as this podcast goes
right now.
I'm a 35 year old female looking to get on HRT.
I've had a hysterectomy five years ago and my PCP is telling me that I cannot have progesterone
now.
I am thankful that she has started me on estrogen and while I do feel a lot better, still have
a lot of anxiety and difficulty going to sleep.
What are your thoughts?
Pretty good timing for this type of question.
And I do want to preface this with this is not medical advice, just my personal opinion
as an HRT provider.
Now, I don't see any reason why you cannot have progesterone.
I have heard this many, many times before and while it is not necessary in terms of
preventing endometrial hyperplasia due to not having a uterus, you would still benefit
tremendously from the effects of progesterone, including the bone protection, breast protection,
and of course the palethora of the mental benefits that you get from progesterone.
Now one thing to consider is, you know, did they spare the ovaries?
Now even if they did a hysterectomy and they left the ovaries, I would say from my experience,
these women are still having hormone deficiency symptoms.
And when I check the blood work, they're objectively low as well.
So even if the ovaries are spared, I'm still seeing from my experience, these women highly
benefit from HRT.
But as far as progesterone use after a hysterectomy, there's no data, literature or research that
shows risk, but you will get benefit.
I want to thank everyone for listening to today's episode of the Hormones Happen podcast
and hope that you were able to find some value in the information that was provided today.
If you have any questions that you would like to have discussed on the podcast, please send
them to the email listed below or message us on the StillCity HRT and Weight Loss Facebook
page.
And remember, you are not alone in the war on hormones.
Stay optimized.