Progesterone is usually calming but can produce a paradoxical anxiety response in some women. It’s called premenstrual dysphoric disorder (PMDD) or neurosteroid change sensitivity and affects about one in twenty women.
It happens because progesterone interacts with GABA receptors in the brain and normally has a calming effect. The same natural level of progesterone can have a stimulating effect in women with PMDD due to a problem with the GABA receptors.
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
Progesterone’s neurosteroid effect is why many women feel sleepier during the luteal phase and pregnancy and why progesterone capsules are usually calming. Progestin drugs from hormonal birth control don’t have the same beneficial effect on the mood or brain because they don’t convert to allopregnanolone.
For women with PMDD, the same interaction between allopregnanolone and GABA receptors can produce anxiety and other intense mood symptoms. It’s not that women with PMDD have a different level of allopregnanolone; they just have a different response to it because of a problem with their GABA receptors.
GABA receptors consist of five subunits which reshuffle and change configuration to adapt to the normal monthly ups and downs of allopregnanolone. With PMDD, the GABA receptors are less able to do that and therefore less adaptive, leading to what researcher Tory Eisenlohr-Moul calls “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 find a way 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 because a higher external dose of progesterone can relieve the PMDD symptoms caused by fluctuating moderate levels of internal allopregnanolone. It’s all to do with the “bimodal association between serum allopregnanolone concentration and adverse mood” and means that lower level of endogenous progesterone or progesterone cream can cause anxiety but 200 mg capsule can be calming. 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, which works well if prolactin is high.