Serious Progesterone Side Effects and Brittle Adrenals – Part 2

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM

Read Part 1

Progesterone side effects can include tender breastProgesterone side effects include many unpleasant symptoms and dangerous conditions.

Nervous System and Muscular Effects

About thirty percent of users experience headache, fifteen percent experience dizziness, and twenty percent experience back or joint pain. Other symptoms include increased sweating, nervous tremors, and speech disorders.

Depression and Sleep

Excess progesterone regulates estrogen receptors down. With fewer estrogen receptors, the brain cannot respond to the hormone in the normal way. Its response to estrogen is needed for serotonin production. While this one of the many progesterone side effects is desirable for those who have insomnia, and many use natural progesterone as a sleep-aid as a result, the lack of serotonin can also cause depression.

Genitourinary and Gastrointestinal Progesterone Side Effects

Twenty-five percent of patients experience some breast tenderness that tend to subside with time, and ten percent experience vaginal discharge. Twenty percent of women will experience abdominal pain and a small number experience bloating, diarrhea and nausea. These GI symptoms are often attributable to activation of systemic candida.

Lowered Libido

Excess progesterone can block the conversion of testosterone to DHT causing a lowered sex drive. This primarily happens to men.

Water Retention

Water retention is likely caused by excess conversion to deoxycortisone, a mineralocorticoid made in the adrenal glands which causes water retention. Those who are prone to the estrogenic effect may also be susceptible to this.

Increased Androgen and Estrogen

Excessive progesterone can also lead to the increase in androgen production and ultimately increase estrogen as the body shunts the excessive progesterone to these other hormones. Estrogen dominance symptoms can emerge, both in males or females.

Low Immune Function

Cellular immunity is an important part of our overall immune system that protects us from viral infections. This is in contrast to bacterial infections that are attacked by macrophages or neutrophils from the innate arm of the immune system. Excessive progesterone suppresses the cellular immune system involving T and B lymphocytes. Upper respiratory infections increases, with more cold and flu-like symptoms.

Miscellaneous progesterone side effects can include:

  • Dry, chapped, itchy skin
  • Transient visual disturbances
  • Hearing difficulties
  • Runaway appetite
  • Weight gain
  • Unusual headaches
  • Male pattern baldness
  • Dry hair
  • Frequency and urgency in urination
  • Extreme thirst
  • Gynecomastia and nipple soreness
  • Lymph node congestion, especially at groin
  • Armpit smell
  • Lower extremity edema
  • Liver ache
  • Cough and weak lung
  • Heart palpitations

Progesterone Side Effects and Liver

Topical progesterone provides a seamless delivery of the hormone into the bloodstream. This delivery method prevents the complications associated with oral progesterone replacement, which gets processed through the gastrointestinal (GI) tract and liver. Because over 80 percent of natural progesterone is metabolized by its first pass through the liver, a much higher dose is required for oral delivery as compared to topical methods.

The liver can be burdened by progesterone side effectsAnyone with liver pathology either clinical or sub-clinical, is at risk with high dose progesterone. Those who have normal liver function according to laboratory tests, but who have sub-clinical and possibly unrecognized liver congestion, are also at risk for progesterone side effects.

While topically progesterone is better compared to oral for those with hepatic constraints, it is not without its own problems. When progesterone cream is administered through the skin, most of it goes into the bloodstream, but some also builds up and accumulates in the subcutaneous fat layer. With long term use, a cumulative saturation effect can result. The body?s self-regulation process is automatically activated, and the body initiates a down-regulation of progesterone receptors, making them more resistant to activation. This is the body?s way of rejecting excessive progesterone in the system. Effectiveness of the progesterone is therefore reduced. Unfortunately, precursors of progesterone such as pregnenolone are shunted to make DHEA, testosterone, and estrogen instead, thus creating a different set of problems as these other hormone levels rise.

Instead of lowering natural progesterone, a frequent clinical mistake is to do just the reverse ? increase progesterone in order to ?normalize? laboratory values.

As the body is subjected to more progesterone, the liver has to work harder and harder, as it has the burden of having to metabolize and detoxify excessive amounts of that hormone. In turn, this puts more stress on the adrenal glands. This vicious cycle only makes matter worse.

Brittle Adrenals

As mentioned above, progesterone is a precursor to many other important hormones. Excessive Progesterone side effects over time can trigger imbalances of other hormones including estrogen, testosterone, aldosterone, and cortisol by a variety of mechanisms. These include shunting, ?stealing?, and down-regulation processes. Those with pre-existing adrenal fatigue in advanced stages are most at risk due to already weakened pathway integrity in the adrenals where they are regulated.

Clinical symptoms that arise from excessive Progesterone side effects can include hyper adrenal function similar to Cushing?s Disease. Symptoms of high cortisol include: hypertension, insomnia, memory loss, feeling hot, edema, irritability, anxiety, muscle weakness, glucose intolerance, increased thirst, and increased urination. Fortunately, this is rare. Such hyper-cortisol symptoms can be fleeting, often lasting only for a short time.

The body?s self regulatory system usually will be triggered to rebalance the hormones and return itself to the normal state. For some, that works. For a small number of people, the body overshoots and enters a state of low cortisol output, similar to Addison?s Disease. This low cortisol results in symptoms that include: extreme fatigue, lymph stagnation, salt craving, low energy, low blood pressure, nausea, vomiting, diarrhea, abdominal pain, and muscle pain. These symptoms also can be fleeting in nature, only lasting a short time. Then the body reverts to the previous high cortisol state. The body is constantly in a state of extreme fluctuation like a yo-yo.

The blood sugar balance can be caused by progesterone side effectsThis is clinically referred to as brittle adrenals. The pattern resembles that of a roller-coaster ride that can occur multiple times during the day. The body is drained nutritionally and hormonally in its effort to effect self rebalancing. Over time, the body is unable to adjust and becomes destabilized. The HPA axis by this time is dysregulated. The body has lost its ability to self regulate and fine tune itself in terms of cortisol output. It is like taking a shower with alternating hot and cold water that is beyond one?s control ? but never the desired warm water.

Ultimately, such extreme swings in cortisol output also destabilizes the body?s metabolic pathways. Blood sugar regulation becomes problematic, and electrolyte imbalance follows along with fluid dysregulation. Like a light switch that has been flipped on and off multiple times continuously ? eventually it breaks. The body is unable to adjust in a timely manner to provide the cushion to handle the extreme hormonal variance. The effort drains the body and resilience is reduced. Such hormonal swings between two extremes, the high cortisol state and the low cortisol state, is a nightmare in the making. This is similar to brittle diabetes, where a person?s blood sugar can quickly go from high to low for no apparent reason.

With the phenomena of brittle adrenals, sufferers are unable to conduct a normal life. Swings between anxiety and depression, low appetite and hunger, low sodium and low potassium, constipation and diarrhea, and low and high magnesium are just some of the vacillating states experienced multiple times during the day. When the cortisol is high, one resorts to using phosphatidylserine, antihistamine, and anti-inflammatory drugs ? bringing some relief. When the cortisol is low, salt water, electrolyte replenishment, and vitamin C can be helpful. Unfortunately, these are simply symptomatic patches and the cycle repeats itself multiple times during the day.

Ultimately, this unrelenting roller coaster ride renders the body to a state of extreme weakness. Toxic reactive metabolite built-up can lead to hypersensitivity reactions, congested extracellular matrix, and receptor site damage. This process usually starts slowly but tend to gather steam as the body becomes weaker over time. Vital signs can become unstable. Multiple and frequent visits to the emergency room become the norm, often only to be told all is well and sent home to ?relax?. Sufferers are eventually bed-bound, because the liver and extra cellular matrix will become congested over time. Overall, the body becomes flooded in a sea of toxin quite toxic with reactive metabolite overload (RMO). The body?s defense is to activate the reactive metabolite response (RMR) as a last resort to reduce toxic metabolites. Multiple organs and systems are put on overdrive to remove as much reactive metabolites as quickly as possible. Intracellular communications and extracellular matrix congestion and burden increases. Inevitably, RMR will lead to additional reactive metabolites being generated. As the body?s toxic load increases, it eventually enters a positive loop of ever reducing stability. Unless multiple laboratory cortisol levels are being drawn and tracked multiple times throughout the day to track the fluctuating burden on the adrenals, doctors are universally lost to understand and eventually give up.

Take caution when dealing with progesterone side effectsThis brittle adrenal phenomena is not exclusively seen in those with progesterone overload, although it seems to be most common. Taking a step back, it is seen most commonly in a body that is weak to begin with at the foundation level, though it may not clinically evident. Other triggers of brittle adrenal include abrupt withdrawal from natural progesterone, inappropriate use of steroids, vaccine toxicity, rampant systemic inflammation, stealth infections, and end stage AFS.

Needless to say, those with brittle adrenals or symptoms resembling this must quickly seek professional help. Most conventional physicians are at a loss as far as knowing what to do. Recovery is possible with a comprehensive plan to stabilize the body?s adrenals, slowly returning cortisol output into balance and reestablishing feedback loops so the body can self regulate. Reactive metabolite volume must be kept under control, while extracellular matrix decongested. This is a very slow process that requires clinical skills, patience, understanding, and some trial and error, because the body is very unstable. The slightest wrong move can worsen the situation, even in the best of clinical hands.


While the use of natural progesterone has its place in rebalancing the body?s hormones, caution is advised when a stage of adrenal fatigue exists. The more advanced the state of adrenal fatigue, the bigger the risk.

Progesterone side effects, toxicity, and brittle adrenals are all very undesirable outcomes that can surface. The proper dosage, frequency, delivery system, and timing must be carefully factored in prior to using progesterone. An exit strategy should be in place beforehand when adrenal fatigue is present. Laboratory tests are unfortunately not helpful in this situation and can be misleading. Close clinical monitoring is required.

Read Part 1

? Copyright 2017 Michael Lam, M.D. All Rights Reserved.

Progesterone side effects


  • Crystal says:

    Thank you for the article. How does one treat the adrenal crash that comes after progesterone overdose? I began treating low cortisol (with a functional medicine doctor) in 2014. My cortisol improved, but progesterone remained low, so he put me on progesterone cream. I took it as prescribed, but the dose was definitely too high for me. I got much, much worse, and progesterone was off the charts high when we tested again. I tapered off and did a lot of detoxing. I never really recovered from that and still have very low cortisol (and low thyroid and progesterone again as a result). Nothing seems to work to bring the adrenals back online, and none of the functional medicine doctors or naturopaths I’ve seen seem to know what to do. How do I get out of this cycle?

    • Dr.Lam says:

      It needs to be done systematically and slowly. I cannot go into it here as it is too complex and is person specific. Find a doctor who knows what to do is key. This is well beyond self-navigation which can make you worse if you are already quite weak.

      Dr. Lam

  • Wendy says:

    What is the best lab test to continually monitor adrenal function?

    • Dr.Lam says:

      Saliva cortisol is commonly used, but it is not helpful if you don’t clinically correlate.

      Dr. Lam

  • Lisa says:

    Thank you for these helpful articles. How does one lower their progesterone cream in the best and healthiest way? I believe I have been using too much and worried about reducing too abruptly. Thank you

    • Dr.Lam says:

      If you do suspect a problem, you should seek professional help to avoid getting worse which can happen when you try to self-navigate when your body is weak or sensitive.

      Dr. Lam

  • Carol says:

    Be careful with progesterone creams: They can build up progesterone in your body. I had profound depression and lost a pound a day. Also be careful with the troche (under-tongue pill): My gums receded and my breasts hurt (and got smaller!) when I used this for just 6 weeks. So now, when I used it at all, I use a dab of over-the-counter progesterone cream on my wrists.

  • Victoria says:

    This is me. I have been suspecting this for some time but have been at a loss how to stop transdermal Progesterone. I started postmenopausal for debilitating hot flashes several yrs ago. Perhaps to make things worse recently I started vaginal estrogen for urethral caruncle and resulting persistent UTI. Cortisol has been tanked last few yrs and taking adrenal cortex not improving it. Eventually essential tremor/tinnitus, loose bowels, now back to constipation and now POTS like symptoms. Rapid breathing with exertion is most frequent and frightening symptom. I feel I can tell when there is saturation of Progesterone….I can smell it. Usually happens at end of pump usage but recently experiencing this intense smell at beginning of pump. I am not sure what my question is. This is all very overwhelming. Hearing that getting off Progesterone is complicated is not very reassuring. Would cutting back very, very slowly over a long period of time be the way to go about this complicated predicament? Thanks

  • Missy says:

    I have been on oral progesterone for years, reaching 300mg last year. I also have hypothyroidism and 4lows of cortisol. A couple of cycles ago I switched to oil applied vaginally. My old symptoms of overwhelming depression and despair have arisen in the second half of my cycle for the last two months. I’m told there is a transition period but this is hell on earth. The oral eliminated my depression but still my progesterone results were rock bottom and bc of the effect on the liver and adrenals I wanted to change to topical. Any advice? Thank you

    • Dr.Lam says:

      Different forms of delivery systems have their own unique characters that have to match the body in order to optimize the clinical outcome. To do it right requires a very detailed history and experience. Do not rely on lab exclusively as you can be mislead. There are many factors that the lab cannot account for in the body’s ability to assimilate progesterone. It is far more complex than what meets the eye.

      Dr. Lam

  • Brian Pearce says:

    Excellent article, although it skipped on the methodology of titration downwards. How quickly can one decrease the Prog dosage? My wife uses oral Prog. She exhibits most of these symptoms. Her hormonal specialist needs to read this article.

    • Dr.Lam says:

      Titration can be very difficult. Everyone is different, and it needs to be holistic in nature to be successful.

      Dr. Lam

  • Molly says:

    Thank you for both Part 1 and Part 2. I often think I must educate my doctor, though he is a functional medicine doc. This is very helpful as he has recommended increasing my progesterone over the years and I keep having trouble when the level goes up. Currently, he has upped me to 40 mg daily but I knew I was having trouble with that dose and your articles have helped me figure out why. Thanks again.