Progesterone Power: The Life-Changing Hormone You're Missing

Often overlooked and considered a “female-only hormone” progesterone has a plethora of benefits in both men and women securing a vital spot as a foundation in HRT. Progesterone is a steroid hormone that is produced via the ovaries in women, testes in men, and adrenal glands in both sexes. It acts as a precursor to other vital hormones such as testosterone and cortisol. It is primarily known due to its effects on regulating the menstrual cycle, supporting pregnancy, and balancing estrogen in women however in men this hormone supports testosterone production and prevents estrogen dominance. Typically, after the age of 30 progesterone levels slowly decline leading to a plethora of symptoms such as poor sleep, mood swings, anxiety, weight gain, and brain fog.

A common scenario that I encounter frequently is a woman in her 30s to 50s who reports frequent exhaustion during the day, irritability, and frustration due to the inability to go to sleep at night. When she does go to sleep, she has difficulty staying asleep and waking up multiple times throughout the night with anxiety or cold sweats. After discussing lifestyle factors, she will usually report despite routine physical activity and moderation in her diet to the best of her abilities a continued weight gain specifically around the midsection. These complaints are common in both a woman who is not currently on HRT or has had a hysterectomy and is only on an estradiol component.

While I hear these complaints in men once testosterone is initiated they usually subside. When a man starts TRT this can increase the amount of progesterone produced in the adrenal glands and although it does not appear there is a large quantitative difference in progesterone between 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 great effect on anxiety and sleep for reasons will be discussing shortly. I personally take 200 to 300 mg of progesterone when I’m having difficulty sleeping and it 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 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 spikes leading to fat storage predominantly around the midsection or belly. 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. 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 T4 toT3, and up regulating thyroid peroxidase. So, basically, it helps to increase the amount of thyroid hormone while improving its efficiency.

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 feelings of calmness and reduced anxiety.

I do want to take a moment to elaborate further on the calming effects of progesterone as this is one of the most beneficial aspects for both men and women. 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, acting as a brake on an overstimulated mind. When there is 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 severe cases, seizures. When progesterone is metabolized one of its primary metabolites, allopregnanolone acts as a powerful modulator of GABA amplifying its brake-like effects on the brain.

Often times when I follow up with a woman who has recently started HRT including progesterone she will describe this as a “turning down the volume” effect on a noisy or chaotic mind. While used less often in a man from my experience I have treated several with oral micronized progesterone when despite optimizing TRT they continue to have anxiety or insomnia and want a natural alternative option to medications such as mood stabilizers or sedatives. Having taken it myself on several occasions I can attest to the feelings of “turning down the volume” on a noisy mind but also a better sense of wellbeing the next day.

Key effects of progesterone, allopregnanolone, and GABA receptor activity result in anxiety reduction, better sleep, mood stabilization, and neuroprotection. 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 need to dive a little 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 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 an injury. Additionally, it helps restore the protective sheath around neurons, preserving their functionality and enhancing brain recovery while mitigating apoptosis which is a natural process that removes damaged or unneeded cells from the body. Lastly, Progesterone stimulates the growth of new neural connections in a process called neurogenesis essentially rebuilding the brain’s neural network after 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? While progesterone comes in a variety of forms such as oral, transdermal, pellets, and patches the most common variations are pills and creams. From the research available today I recommend oral micronized progesterone as a first-line therapy due to its conversion to allopregnanolone via the liver and this is where all of the calming and sleep-promoting effects come from however no two people are the same and some women are very sensitive to these effects to a point where it may be too much. In these cases, the cream is a better option due to the ability to bypass the liver and avoid the conversion to allopregnanolone.

One concern with the creams is that due to the larger size of the progesterone molecule, it may not be adequately absorbed into the capillaries causing less protection against estrogen dominance. I have heard several experts dispute this claim and report that while on progesterone cream checking levels is tricker because it will under sense on blood work and over sense on saliva testing.

How much to give and when to give it are also highly controversial due to the variabilities in thought processes among experts and the lack of study designs used for this specific population. Regarding dosage, this varies anywhere from 50 mg to 400 mg, and I personally start my patients off at 200 mg which seems to be a great dose for achieving anxiety reduction and promoting sleep. 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 every other day and even every day. There is speculation that the progesterone receptor can be down-regulated with everyday use causing a desensitization effect in addition to down-regulating the estradiol receptor.

I typically start most of my patients on every other day dosing but often times what I hear is that on the days they do not 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 of cases that the progesterone will decrease the estradiol levels, but this is an easy fix while on estradiol replacement. 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 what I was talking about.

Q&A

Question: Can TRT be injected like insulin?

Answer: I assume he is asking if testosterone can be injected subcutaneously, and the answer is absolutely. This is often the administration route I recommend to men who have never taken it before. Now there are a couple things to keep in mind here one is the type of carrier oil used in the testosterone and the second is the needle size. I have all of my testosterone compounded with grapeseed oil which is less viscous or thick and less inflammatory on the body compared to its commercially available counterparts cotton seed and sesame seed oil. I also provide my patients 27 gauge, ½ inch needles which are the same ones used to inject insulin. These small changes make injecting twice daily more manageable. The biggest difference between intramuscular and subcutaneous injections is the rate at which it is absorbed. Intramuscular injections due to having a greater blood supply to the area will be absorbed quicker. This is not a significant factor when injecting at least twice per week.

Question: I am a 38-year-old man 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. Why is my testosterone level lower?

Answer: This is more common than you guys think however it has 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 the testosterone from a needle and thinks that it’s making too much. Assuming he’s using testosterone cypionate that means he is getting the peak effect of the medication in about 3-4 days and half of the medication is out of his system in a week. Now going one week further means that he is having half of the half out of the system. So from the initial 200 mg he is only working with about 50 mg now but there are a lot of variables to this and I am just making a broad assumption based on normal half-lives of a medication. 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 it your natural production would start again but in that 2 week window, you are pretty vulnerable. So as I’ve said before I recommend at least twice weekly injections to avoid this issue.

Question: I’m a 39-year-old female looking to get on HRT. I had a hysterectomy 5 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?

Answer: While this is not medical advice, I do not see any reason why you cannot have progesterone. I have heard this 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 and breast protection properties.

Steel City HRT and Weight Loss is a clinic that provides safe and affordable hormone replacement therapy (HRT) and weight loss to men and women in Pueblo, Colorado. If you have any questions or would like to schedule an appointment to discuss treatment don't hesitate to call, text, or email at [email protected] or (719) 669-4223.