Dr. Katharina Dalton had pioneered using progesterone in suppositories or injections in large doses to treat severe PMS.(1) These women faced monthly havoc with high anxiety, fluid retention, sore breasts, feeling suicidal and homicidal, experiencing seizures, and excruciating migraines. Research conducted by Drs. Hargrove and Maxon, (2) demonstrated that oral use of progesterone was also effective if the progesterone powder was micronized (very small particle size) and delivered in edible oil. The minimum starting dose was 400 mg in divided doses and increased as needed to address the clinical symptoms. Doses could go as high as 2500 mg daily during the luteal phase and sometimes into the first 3 days of bleeding. Women used other dosage forms such as lozenges, suppositories, creams, gels, and rectal solutions to address breakthrough symptoms and administer the amount of progesterone needed for symptom relief.
This therapy was very successful for most. However, there are circumstances when progesterone dosing is troublesome. Here are some of the reasons that progesterone dosing might be problematic.
The Dose of Progesterone is too Small
We learned from the severe PMS cases that using MORE progesterone immediately would resolve mood issues, water retention, breast pain and tenderness, and headache easily. Often these symptoms are listed as side effects of using progesterone. These symptoms are all related to too much estrogen effect. Resolving this immediately with additional progesterone will bring comfort within hours. Unfortunately, many practitioners and their patients think that the solution is to use less progesterone. This will also stop some of these symptoms, but all the benefit of progesterone is lost. Evaluation and help with estrogen excess can help.
Progesterone Sensitizes Estrogen Receptors
Women with hysterectomy are often supplemented with estrogen only. Their practitioners tell them they no longer need progesterone since they do not need to shed the build-up of endometrial tissue. However, this dogma ignores the fact that the body has progesterone receptors all over the body. Progesterone is also normally made in the adrenal glands and independently by Schwann cells in the nervous system tissue. In the brain, progesterone is a neurosteroid and is made independently of the endocrine glands. Progesterone is a precursor of the most powerful brain hormone, allopregnanolone. These women have problems with anxiety and sleep that progesterone use can solve very easily. When a woman is on estrogen already and progesterone is being added, the stimulation of estrogen receptors magnifies the estrogen effect. (3) Using about half the amount of estrogen when progesterone is started is prudent or be ready to use more progesterone immediately if uncomfortable with breast swelling, fluid retention, anxiety and headache occur. Progesterone is exactly the hormone needed. Conventional practice dooms women to decades of sleep-aiding drugs, antianxiety and antidepressant drugs. Many of the hysterectomies performed are due to a chronic lack of progesterone. According to Dr. Katharina Dalton, these women need more progesterone than those with normal menopause.
Women have been propagandized into believing estrogen is the most important hormone for women, when in fact, it is progesterone that is the most abundant, followed by testosterone and then finally estrogen.
Progesterone is a Precursor for Hydrocortisone
When women have had chronic stress, their ability to make the powerful anti-inflammatory hormones, hydrocortisone and metabolites is diminished. (4) Women have had the benefit of abundant amounts of progesterone created during the luteal phase each month bestowing more resilience for the adrenal glands. If this deficiency exists when beginning progesterone, the body will divert that progesterone to restore the depleted hydrocortisone and metabolites. There may not be enough progesterone used to restore hydrocortisone and balance the effects of estrogen. The expected symptoms of excess estrogen such as water retention, breast tenderness, and headache can show up. Using more progesterone immediately will resolve these symptoms.
Progesterone causes bleeding
Progesterone is the endometrial secretory hormone. Expect that when enough progesterone has been used, the accumulated tissue will shed. This is a good thing. In the case of heavy bleeding in perimenopause, progesterone will oppose the excessive build-up by estrogen if used during the first half or follicular time of the cycle. Follicular levels of progesterone are produced by the adrenal glands and are essential to prevent too much endometrial buildup. Heavy bleeding during perimenopause is a common cause for undergoing hysterectomy but could be easily avoided if progesterone is used. Using extra progesterone when stressful situations occur can prevent later bleeding. When bleeding does occur, the build-up from the estrogen stimulation unbalanced by enough progesterone is now being shed. Unfortunately, at this point, women seek out their practitioners who may find no endometrial buildup.
Candida is Overgrowing
When the gut microbiome is disordered, starting the use of progesterone allows existing Candida colonies to overgrow even more. Symptoms such as brain fog, increased sinus problems, constipation or diarrhea, vaginal burning and itching, outbreaks in the skin, and blood sugar swings ensue. (5) Progesterone may be badly needed but it will be important to manage Candida overgrowth first. When progesterone is added, it may be helpful to use non-oral administration. Some organisms can produce estradiol. Some organisms or their excretion molecules can interfere with hormone activity by binding to hormones. Pregnenolone, a progesterone precursor, has less Candida influence and is worth exploring.
Progesterone Causes Sleepiness or Grogginess
One of the metabolites of progesterone is allopregnanolone. Allopregnanolone may be as sedating as barbiturates. The amount of conversion varies with individuals. This seems to occur most frequently with oral administration. Switching to vaginal, rectal, or topical dosage forms may help.
Mast Cells Release Histamine – When Progesterone is Deficit
“Mast cell activation syndrome (MCAS) causes a person to have repeated severe allergy symptoms affecting several body systems. In MCAS, mast cells mistakenly release too many chemical agents, resulting in symptoms in the skin, gastrointestinal tract, heart, respiratory, and neurologic systems. Mast cells are present throughout most of our bodies and secrete different chemicals during allergic reactions. Symptoms include episodes of abdominal pain, cramping, diarrhea, flushing, itching, wheezing, coughing, lightheadedness, rapid pulse, and low blood pressure. Symptoms can start at any age, but usually begin in adulthood.” (6) Mast cells contain receptors for sex and adrenal hormones. A dominance of estrogen tends to favor histamine reactions. Progesterone can mitigate the histamine release but should be in adequate amounts to balance estrogen. If insufficient progesterone is used, estrogen is magnified, and histamine-type reactions can occur.
The Estrogen Burden is Excessive
Frequently practitioners measure estradiol and assume that the results reflect the amount of estrogen activity. Excesses of estrogen can be found with estrogen metabolites, xenoestrogens from insecticides, pesticides, and heavy metals occupying estrogen receptors. (7) With deficiencies in sulfation and methylation, the liver will not conjugate estrogen for elimination. Some bacteria overgrowing in the gut microbiome will secrete beta-glucuronidase. This enzyme removes the conjugates from estrogen and allows estrogen to go back into circulation. This is called entero-hepatic recirculation. Identifying these issues and treating them can help restore the balance between estrogens and progesterone.
Heavy Metals block Receptors for Progesterone
When heavy metals such as mercury, cadmium, aluminum, lead, and more are part of the body burden introduced by amalgams, environment, and other intakes.
According to Dr. David Quig: “Hg [mercury] may also interfere with progesterone metabolism without affecting serum levels of progesterone. In vitro studies indicate Hg [mercury] binds to a free sulfhydryl group on the progesterone receptor and may thereby diminish progesterone binding and cellular response.” (8)The use of estrogen alone without progesterone balance can lead to copper toxicity. (9)
Exhaustion of CoFactors and CoEnzymes
Every biochemical reaction in the body requires cofactors which are essential minerals and coenzymes which are vitamins needed to complete the action. Progesterone metabolism is particularly dependent upon vitamin B6 and magnesium. When adding hormone supplementation, pay attention to adequate nutrition and/or nutrients. Dr. Guy Abraham engineered a nutrient product that he felt addressed the nutrient needs that were not always met in women with PMS symptoms. His paper outlines some of the nutritional needs in PMS. These nutritional guidelines also apply to menopause. (10)
Duped into Believing that Synthetic Drugs are Progesterone
Prempro and Provera contain a synthetic progestin called medroxyprogesterone. The Mirena IUD coil contains levonorgestrel, the patch, CombiPatch contains norethindrone acetate. Activell contains norethindrone acetate. These are just a few examples. Many are told by their prescribers that they are using progesterone but are really using these altered molecules. This will directly impact the progesterone receptor. Sometimes the effect is progesterone-like, such as shedding of the endometrial lining. Sometimes, the receptor is blocked by the progestin and no progesterone-like effect happens. Only actual progesterone achieves the expected results and helps balance estrogen.
Allergy to Progesterone
It seems strange that women could be allergic to their own hormones. Antigen-antibody complexes are proteins and steroidal hormones like progesterone are not proteins. Progesterone can and does bind to a carrier protein and it is this complex that can become reactive. Allergy desensitization techniques can be used to correct this, and some specialty labs have developed tests to measure this. (11)
This list is not exhaustive.
The deficiency of progesterone is responsible for much misery. Many women find progesterone supplementation life-changing and easy. However, there are some women who find progesterone supplementation troublesome and claim that they can’t use it. With guidance from a practitioner, sorting out the underlying causes could bring relief.