Progesterone is usually soothing to mood but can sometimes cause anxiety. A negative mood reaction to progesterone is called neurosteroid change sensitivity or premenstrual dysphoric disorder (PMDD) and affects about one in twenty women.
Here’s everything you need to know about progesterone and mood.
Contraceptive progestin drugs are bad for mood
Progestins are not the same as the body’s own progesterone, so shouldn’t come into this conversation. Unfortunately, many doctors, journalists, and even scientists confuse progestins with progesterone and so say “progesterone is bad for mood” when they really mean progestins are bad for mood.
Contraceptive progestins such as levonorgestrel, drospirenone, and norethisterone have all been linked with anxiety and depression, but mood symptoms from birth control are drug side effects, not PMS or PMDD.
Progesterone and the brain
For most women, progesterone is good for mood because it converts to a neurosteroid called allopregnanolone which calms GABA receptors in the brain. Progesterone’s neurosteroid effect is why progesterone capsules are sedating and why times of high progesterone (luteal phase and pregnancy) cause sleepiness. The progestin drugs of hormonal birth control do not convert to allopregnanolone, therefore are not soothing to mood.
For women with PMDD, allopregnanolone dos not calm GABA receptors but instead can produce anxiety and other intense mood symptoms. Women with PMDD have the same level of allopregnanolone; just have a different response to it because of a problem with GABA receptors.
GABA receptors consist of five subunits that reshuffle and change configuration to adapt to the normal ups and downs of allopregnanolone. With PMDD, the GABA receptors are less able to adapt to changing levels of allopregnanolone. The result, according to researcher Tory Eisenlohr-Moul, is neurosteroid change sensitivity and the mood symptoms of PMDD.
Conventional treatment of PMDD
Conventional treatment for PMDD includes:
- SSRI antidepressants to modulate GABA receptors, and/or
- hormonal birth control to shut down ovulation and progesterone.
The problem with this approach is that:
- SSRI antidepressants may increase the risk of osteoporosis.
- Contraceptive progestin drugs carry their own set of mood side effects.
- Women need ovulation and progesterone for long-term health. According to Professor Jerilynn Prior, “regular menstrual cycles with consistently normal ovulation [and progesterone]…will prevent osteoporosis, breast cancer and heart disease.”
The better approach is to stabilize GABA receptors and therefore tolerate the normal ups and downs of progesterone.
Natural treatment of PMDD
- Reduce histamine and mast cell activation, which reduces histamine-induced mood symptoms and may alter GABA receptors. Histamine is the main driver of the swelling and irritability attributed to “estrogen dominance.” Histamine is one aspect of chronic inflammation which is a known driver of premenstrual mood symptoms. Read The role of histamine and mast cells in PMS and PMDD.
👉 Tip: For many of my patients, avoiding cow’s dairy is the simplest way to reduce a mast cell or histamine response. Another potentially beneficial effect of avoiding dairy is to reduce exposure to a casein-derived neuroactive peptide called BCM7, which affects levels of GABA.
- Magnesium, which supports a healthy GABA response and relieves PMS by “normalizing the action of progesterone on the central nervous system.” The best form is magnesium glycinate or bisglycinate because the amino acid glycine also calms GABA receptors.
👉 Tip: The therapeutic dose is 300 mg of elemental magnesium, so read the label carefully. Most magnesium capsules contain 100 mg.
- Vitamin B6 (pyridoxine) has done well in at least one clinical trial for PMDD. It works by boosting GABA, lowering prolactin (high prolactin is another cause of premenstrual mood symptoms), and promoting the healthy clearance of histamine. The therapeutic dose is at least 50 mg pyridoxine or pyridoxal-5-phosphate, but I sometimes prescribe more to be taken during the days of mood symptoms. Check with your clinician because long-term high-dose vitamin B6 can cause nerve damage.
👉 Tip: I get the best results with magnesium plus vitamin B6 plus the amino acid taurine (because taurine calms GABA receptors).
- Natural progesterone capsules. It’s all about the dose. Because of the bimodal association between serum allopregnanolone and adverse mood, you might feel better on a 200 mg capsule compared to a cream. In other words, anxiety can be relieved by moderate dose progesterone but worsened by low or high dose. There are only a few studies of progesterone for premenstrual mood, and unfortunately, many of the studies used huge doses of 400 to 1200 mg that caused side effects rather than benefits.
Progesterone is also an effective treatment for premenstrual migraines.
Milder PMS symptoms
Milder premenstrual symptoms (PMS) that occur only during the final few days of the cycle are not neurosteroid change sensitivity like PMDD. Instead, they are simply withdrawal from allopregnanolone. PMS responds to many of the treatments listed here as well as progesterone cream, iodine (especially if you have breast pain), and the herbal medicine vitex (if you have high prolactin).