Special Considerations When Using Progesterone Cream

For the most part, progesterone cream is extremely well tolerated. However, progesterone can significantly affect how the body functions, and people tend to react to hormones differently, so some people may experience side effects from progesterone. When side effects occur, they are usually temporary. A major benefit of bioidentical creams is that it is easy to titrate the dose or change the area of application and thus reduce or avoid side effects. 

Side effects may include:

• Headaches and/or dizziness (extremely rare)
• Acne (uncommon)
• Sleepiness (only when used orally)
• Menstrual spotting or heavier periods
• Nipple tenderness in women

In most cases, progesterone cream actually eliminates the first three side effects listed. 

Headaches - Women with migraine headaches secondary to estrogen may find that their headache disappears within minutes after using progesterone. In the rare cases where headaches do occur as a side effect of progesterone, Dr. Platt’s protocol recommends either temporarily reducing the dose or applying the cream on the inner ankle, which allows the progesterone to attach to many receptor sites as it moves through the bloodstream before reaching the head.

Acne, which can be triggered by elevated testosterone, often improves with progesterone because the progesterone can lead to a decrease in testosterone production in women who overproduce it. This is often seen in cases of polycystic ovarian syndrome (PCOS). However, progesterone can also downregulate into other hormones including testosterone, and thus can cause acne. If this is the case, I would decrease the dose or ask the patient to apply it on her ankle. This side effect should eventually disappear. If the problem persists, obtaining a prescription for spironolactone, 25–50 mg/day, may be helpful. This drug can block the production of testosterone.

Sleepiness or fatigue is rare as a side effect of progesterone cream, but it is common with any type of oral progesterone, including Prometrium, progesterone troches, and drops placed under the tongue. This is because any form of oral progesterone goes directly to the liver, where it converts into allopregnanolone, which does cause fatigue. This is why Prometrium is always prescribed at bedtime. With progesterone in cream form, on the other hand, fatigue from hypoglycemia is usually eliminated, since progesterone controls insulin.

Fatigue - Because progesterone can block adrenaline, a person starting on progesterone cream may experience a noticeable loss of energy, especially if he or she has been “living on adrenaline” (for example, those with a type A personality). If thyroid levels are on the lower side of normal, excess adrenaline can sometimes mask the fatigue typically associated with subclinical hypothyroidism. In this case, the person, when first starting progesterone cream, can experience significant fatigue, which can be eliminated by adding thyroid medication.

In some people, the sudden drop in adrenaline has a dramatic effect on the body comparable to the sudden withdrawal from a psychoactive medication, and can cause unpleasant side effects, such as uncontrollable crying. I have seen this most often in people whose level of adrenaline—the rage and anger hormone—was very high. The crying jag is most likely an expression of relief and is a temporary phenomenon.

Rarely, some people show an increase in adrenaline-like symptoms such as palpitations, nervousness, and trouble sleeping. The cause for this is unclear. It could be the body responding to the sudden drop in adrenaline by increasing the production of this hormone. Or it could be related to progesterone blocking the insulin receptor sites of brain cells, which in effect lowers the sugar level inside the brain cells, causing the release of adrenaline to raise the sugar level. In these cases, I recommend reducing the dose of progesterone temporarily, allowing the body to acclimate to it more slowly, and then gradually increasing the dose to an effective level. Or they may have Type III diabetes, insulin resistance to the brain.

If menstrual spotting occurs when a woman starts using progesterone cream, or if the menstrual flow is heavier, it is often because the progesterone is bringing about healing of the uterus. These effects usually go away after several months. In some cases, progesterone can initially downregulate into estradiol (one of the three forms of estrogen), in which case the progesterone dose may actually need to be increased to balance the increase in estrogen. This side effect is more commonly seen when using a low dose (2%) over-the-counter progesterone cream.

Women trying to conceive may want to replicate the hormonal pattern of the normal menstrual cycle, which means not using the progesterone cream from day one to day ten of their cycle.

Because there are many progesterone receptor sites around the nipples, some women may experience tenderness in this area when first starting on progesterone cream. In these cases, the dose can be cut in half until the discomfort disappears and then returned to full dose.

Progesterone causes apoptosis (death) of breast cancer cells. For this reason, I consider progesterone beneficial for women who have or have had breast cancer that is progesterone receptor site positive. Most oncologists would probably disagree. However, their knowledge of progesterone is usually limited to synthetic progestins, such as Provera (medroxyprogesterone), which can cause the same side effects as estrogen: breast cancer, blood clots, and weight gain. Bio-identical progesterone, which behaves in the body quite differently from synthetic progestins, has none of these side effects.

Remarkably, the State of California has, for some reason, decided that bioidentical progesterone causes cancer. This is in spite of the fact that in the 70 years of its existence it has never been demonstrated to cause cancer. Ironically, estrogen is a known cancer-causing chemical, yet it is injected into animals to fatten them (even though injecting a carcinogenic substance into an animal for this purpose is illegal).