Serious Progesterone Side Effects and Brittle Adrenals

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

Understanding progesterone side effects are not always easyThe widespread and common use of natural progesterone (hereafter referred to as progesterone) for hormone balance and menopausal symptoms, especially estrogen dominance, has potentially important negative clinical implications when used by those with a weak body – such as those with Adrenal Fatigue Syndrome (AFS). Excessive progesterone can cause imbalances with many other hormones in the body, making progesterone side effects and toxicity both serious and hard to identify. Extreme caution should be used when considering progesterone, and this article details why.

Although a natural compound, inappropriate use of natural progesterone can worsen sub-clinical liver congestion, trigger multiple progesterone side effects and toxicity symptoms, and worsen adrenal fatigue. Abrupt withdrawals can also result in adrenal crashes and potentially cause irreparable damage. In the extreme, it can lead to a state that is known as brittle adrenals, where the body exhibit fluctuating symptoms resembling both extremes of cortisol level (too high and too low). Fortunately, this affects only a small number of AFS sufferers, but if you are one of them, life is downright miserable.

Short-Term Improvement

When a patient complains of fatigue or menopausal discomfort to a doctor, the typical medical workup consists of investigating thyroid function, anemia, and metabolic issues. Female and male hormones are often investigated by way of saliva or serum laboratory tests. Functional or alternative medicine practitioners commonly obtain diurnal cortisol, estrogen, progesterone, DHEA, and testosterone as baseline hormonal information through laboratory studies. While most laboratory studies are normal, DHEA and progesterone level are often low.

At this point, patients are told they have a hormonal imbalance and will need natural hormone replacement that can include estrogen, progesterone, and sometimes also testosterone. Typically, patients are also given thyroid support, vitamin C, vitamin B, glandulars, herbs, DHEA and pregnenolone at the same time. Such a multi-hormone approach is designed to replace diminishing hormones the body may be experiencing. The key to success or failure of such an approach lies largely in the dosage and delivery system of the hormone replacement. Some doctors tend to be quite aggressive, while others are more conservative.

This symptom patching “shotgun” approach often produces positive results in the beginning. For most sufferers, the fatigue of unknown origin improves. Anxiety tends to improve as well, due largely to progesterone side effects. There is a general increase in energy, with fewer energy slumps. Sleep tends to improve from natural progesterone’s sedative effect. A sense of calm returns. Symptoms consistent with estrogen dominance, include: PMS, water retention, brain fog, anxiety, and heavy menses. Because progesterone opposes estrogen, these symptoms may subside if a person is indeed in estrogen dominance. For some, the benefit is significant and remarkable. They are given what appears to be a new lease on life. For the first time in years, many report feeling vibrant and energetic with a positive outlook on life.

Long-Term Decline

It can be unpleasant dealing with progesterone side effectsUnfortunately, for most this honeymoon does not last indefinitely. While some people continue to do well on such a program, many report this multiple hormone replacement approach gradually loses effectiveness over time. Those who are already in advanced stages of adrenal fatigue prior to beginning such program are particularly vulnerable to progesterone side effects. Over months or years, there is a slow but gradual loss of the positive clinical outcome as compared to the initial benefit. As time progresses, many return to their doctor for more help.

To achieve the same effect, physicians generally recommend more hormone replacement by way of stronger dose. Thyroid replacement, for example, progresses over time from primarily a low dose T4 replacement program, to a combination of T4/T3 replacement, then finally to a high dose strong T3 replacement. In like manner, the dosage of transdermal natural progesterone may start at a 20 mg dose, but ultimately can be much more. Sufferers may be switched to other delivery systems, such as sublingual forms, to enhance absorption. Oral progesterone favored by most physicians may start at 100 to 200 mg per day but can be increased significantly over time.

Is this the right strategy? Let us take a step back and understand what progesterone actually do first physiologically in our body.

Natural Progesterone 101

Progesterone is one of the major female hormones, along with estrogen, produced by the ovaries. These two hormones work together to regulate a woman’s menstrual cycle. Natural progesterone has an identical chemical structure to that made in a woman’s body by the ovarian corpus luteum. It is not the same as the synthetically derived progesterone referred to as progestins, which are chemically modified and recommended by conventional doctors. Progestins have the opposite effect to natural progesterone. They are used as morning after pills to trigger abortions and in birth control pills. To be clear, this discussion deals only with natural progesterone.

Progesterone is a calming hormone. It opposes estrogen. It is known as a lipophilic hormone. In other words, it “loves fat” such as adipose tissues. It tends to stay in areas of the body where such tissue is prominent, such as the abdomen and organs. All steroid hormones love fat, including estrogen and testosterone. However, progesterone loves fat the most out of them all. When hormones are trapped in fat, the body can only metabolize a limited amout a day. One study reported that it took four months for women to clear half of the 42 mg per day dose they used for 40 days. Excessive progesterone therefore may lead to accumulation in the body. This accumulation can have negative effects.

Natural progesterone is available in pill form, as a topical gel, vaginal gel, sublingual spray, or as an oil. Under normal conditions in healthy individuals, 20 to 30 mg a day for women and 6 to 10 mg a day for men is considered a physiological amount. There usually are little, if any, progesterone side effects.

Progesterone side effects can be caused by hormonal pillsHowever, the same cannot be said for those with adrenal fatigue or those who take high doses. Many in advanced stages of adrenal fatigue cannot tolerate natural progesterone, even in small amounts. Healthy women on high dose progesterone can develop toxicity symptoms over time.

This occurs for many reasons, including progesterone’s own intrinsic properties as well as it being a precursor to many other hormones. A flow-through to other hormones includes estrogen and its metabolites, testosterone and its metabolites, DHEA, aldosterone, and ultimately, cortisol can occur.

Improper Use of Natural Progesterone

To understand this, first it is helpful to know how natural progesterone should be used and the many ways its inappropriate use can be problematic.

Progesterone in the Wrong Place

As mentioned above, natural progesterone cream is lipophilic in nature. It tends to accumulate in our adipose tissue. For fast delivery, application to areas with ample blood supply is preferred. This include the neck, wrist, under the tongue, and inner arm. Not everyone does well with fast delivery, and adrenal crashes may be triggered. Those in advanced stages of AFS tend to have the biggest risk. For these people, application to fatty areas such as the abdomen may be most appropriate because the release is gentle and slow. The proper location for applying the cream, therefore, depends on each person’s needs and state of adrenal fatigue.

Progesterone Side Effects Mimic Estrogen Dominance

Estrogen dominance exhibits symptoms such as: water retention, anxiety, breast tenderness, spotting, dizziness, hot flashes, fatigue, headaches, nausea, and irritability. These symptoms may become worse when first beginning natural progesterone.

Because estrogen and progesterone receptor sites are very similar at the cellular level, estrogen receptor sites can ‘wake up’ when occupied by progesterone molecules, enhancing the action of estrogen for a short period of time. It is easy to draw the conclusion that this is a sign the body is responding well to the progesterone, and sufferers are encouraged to “brave through” this estrogenic effect, as it is supposed to eventually go away. However, ignoring the underlying dysfunction when alerted by the body is a recipe for disaster.

Fortunately, this is usually short lived for most, lasting a few days to a few weeks. For some, however, this is just the beginning of their nightmare. The more advanced the adrenal fatigue, the higher the risk of this phenomena. Clinically, this is more prevalent in those with sensitive or thin bodies as well. It points to underlying receptor site dysfunction or liver congestion.

Stress Interferes with Progesterone

If there is concurrent stress that activates the body’s stress handling HPA hormonal axis, as is the case in adrenal fatigue, natural progesterone side effects can make matters worse. In other words, if your body’s ability to deal with stress is compromised, progesterone does not improve symptoms.

Stress can increase progesterone side effectsStress triggers the body to put the adrenal glands on overdrive to increase output of the anti-stress hormone cortisol. This is what happens in the early stages of adrenal fatigue. Cortisol, unfortunately, competes for progesterone receptors. The higher the level of stress experienced, the more cortisol the adrenals produce. This means that those receptor sites may be occupied by cortisol rather than progesterone. This leads to reduced progesterone availability to cells. Also, progesterone is a precursor to the synthesis of cortisol. In times of stress, progesterone may be shunted to make more cortisol, resulting in less progesterone being available to the cell as well. Multiple mechanisms therefore can result in lower than normal levels of free progesterone during stress, while estrogen dominance symptoms rise. This may be reflected in laboratory test showing lower than normal progesterone levels in absolute terms, or a low progesterone to estrogen ratio. Physicians not alert to this lowered progesterone level in times of stress may prescribe progesterone in their best intention to increase the progesterone level.

In other words, if you are not managing your stress levels properly, the natural progesterone cream you are currently using may not be effective. Physicians may then prescribe cortisol. Sometimes it can be helpful, but cortisol has its own set of problems, including tolerance, resistance, dependency and withdrawal issues. In addition, cortisol can also lead to loss of magnesium and potassium, further complicating the clinical picture and triggering electrolyte imbalances. Menstrual bleeding may increase as estrogen dominance symptoms worsen. High dose progesterone is often prescribed to control or offset estrogen overload and excessive bleeding. This can trigger a host of side effects and toxicity issues.

Long-Term Overdose is Possible

While a one-time overdose of natural progesterone cream is rare (except in people who are very weak or sensitive), the body’s ability to handle excessive progesterone can be overwhelmed over a long period of time. Progesterone side effects and toxicity are eventually triggered due to a cumulative saturation effect of progesterone in the cells. The common belief that natural progesterone is “harmless”, even in high doses, is quite naïve.

Abrupt Cessation Can Trigger Withdrawal

Stopping progesterone abruptly without proper titration can also be problematic. Many have experienced a huge wave and additional surging of progesterone as it comes out of our tissues soon after abrupt withdrawal. It is a very unpleasant experience. An aldosterone surge can occur that leads to electrolyte imbalances – which in severe cases requires hospitalization.

Progesterone Side Effects

Progesterone 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

Progesterone side effects can include tender breastTwenty-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 side effects 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 side effects suppress 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 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.

Anyone 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.

The liver can be burdened by progesterone side effectsInstead 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 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 can include a hyper adrenal function similar to Cushing’s Disease. Symptoms of high cortisol include an inability to tolerate glucose, weakness of muscles, feeling irritable or anxious, feeling too hot, feeling thirsty, urinating more than usual and memory loss. Fortunately, this is rare. Such hyper-cortisol symptoms are fleeting and last only for a short period.

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: feeling nauseated, vomiting, diarrhea, abdominal pains, lacking energy, low blood pressure, craving salt, pronounced fatigue, muscle pain or lymph stagnation. These symptoms also can be fleeting in nature, disappearing relatively quickly. Then the production of cortisol catches up and overloads the body with cortisol once again. In these cases, the body is wracked with fluctuations with cortisol hitting both highs and lows.

Those that suffer like this are said to have brittle adrenals. The pattern of cortisol throughout the day is like a roller coaster with multiple ups and downs. The nutritional reserves and hormonal balance are strained over, and over each time the body tries to rebalance. It eventually reaches a point where the body cannot respond properly and loses stability. Hormonal axes like the Hypothalamic-Pituitary-Adrenal (HPA) axis will be malfunctioning. The ability to regulate and fine tune cortisol output is lost. Cortisol levels careen wildly and seemingly randomly, unable to stay at a healthy equilibrium point. This can be compared with brittle diabetes, a form of diabetes which can see very quick swings in blood sugar levels with no apparent reason.

The body’s metabolism and other functions will also feel the effects of the extreme cortisol swings. The ability to maintain fluid balance diminishes and is lost, also preventing the body from being able to maintain its electrolyte balance. Blood sugar levels, too, are unable to be properly regulated. Many systems in the body are thrown out of order once the cortisol balance is broken. The body cannot provide a cushion against the ill effects of this hormonal roller coaster. Every time the body tries and fails to push cortisol back towards its equilibrium, it uses up more and more resources and reduces its resiliency.

The blood sugar balance can be caused by progesterone side effectsPeople with brittle adrenals suffer a disrupted life. The violent swings in hormone levels produce wild swings in mood and physiology. Sufferers vacillate between loss of appetite and hunger, depression and manic anxiety, potassium and sodium overload, diarrhea and constipation, too much and too little magnesium, among others. Using anti-inflammatory or antihistamine drugs, or phosphatidylserine can help with high cortisol. Symptoms of low cortisol can be eased using Vitamin C or rebalancing electrolytes and salt water. However, with the constant and unabating swings occurring multiple times within a single day, these remedies only provide temporary short-term relief.

As the body continues to lose control and do damage to itself, it becomes weak as it completely drains the body’s reserves. The body’s filtration and detoxification systems are unable to function as the body has no resources to keep them functioning properly. Metabolic and functional byproducts are not cleared away and build up to toxic levels in the body. This can cause further ill effects such as hypersensitivities and damage to receptor sites. Symptoms become so pronounced that the sufferer becomes bed-bound and visits to the hospital emergency room become routine. Even so, doctors cannot identify any malady, and the suffer is only prescribed rest and relaxation.

The body is overwhelmed by the deluge of toxic metabolites, a state known as reactive metabolite overload (RMO). Faced with this, the body engages a reactive metabolite response (RMR) as a final last ditch effort to counter the toxic load. The body tries to run its detoxification systems at full power to flush out the toxins. However, with all the body’s systems already misfiring, this response is unsuccessful and ends up producing even more toxic metabolites. This positive feedback loop keeps the body spiraling out of control. Any single cortisol test will only tell a fragment of the bigger picture, so unless a sequential set of tests is done and tracked throughout the day, doctors will not be able to see what is actually going on, much less explain it.

The phenomena known as brittle adrenals is not exclusive to those suffering from progesterone overload, although it seems to be most common. Tracing to the root of the issue, brittle adrenals tend to show up in those that do not have a stable foundation of health. Brittle adrenals can have triggered such as steroid use, systemic inflammation, stealth infections, increased toxic load, advanced adrenal fatigue, or stopping progesterone supplements or creams.

It is important to seek professional help if you find yourself with symptoms of brittle adrenals. Conventional doctors will usually not be able to explain what is going on or offer a route to recovery. A proper recovery plan needs to gently nudge cortisol output into a regular pattern. As cortisol output levels come back towards equilibrium, the body will naturally reestablish the healthy feedback loops that keep hormone levels in balance. The body will begin to regain the ability to regulate these levels. Toxic metabolites from the body’s own functions must be controlled while the body’s detoxification functions are slowly rehabilitated, and the extracellular matrix decongested. Successfully helping the body through this requires patience, knowledge and some trial and error. The body will be very unstable at first, so even an experienced clinician needs to take care not to make the body worse.


Take caution when dealing with progesterone side effectsWhile 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.

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

Dr. Lam’s Key Questions

Yes, it can, but because males do not require as much progesterone internally, that is usually not a factor. Given the high amount of estrogenic compounds that we are all exposed to, regardless of whether we are male or female, it is good to consider low dose progesterone for a male to offset estrogen when indicated.

If a male has too much estrogen in his body, he may develop estrogen dominance and cause problems in the prostate, such as BPH or Prostate cancer. Taking progesterone may help to balance this out.

Progesterone side effects