Why Progesterone Is Both Good and Bad for Mood (and How to Treat PMDD)

Mood effects of progesterone.

Progesterone is usually soothing to mood but can sometimes cause anxiety.

A negative mood reaction to changing levels of progesterone is called neurosteroid change sensitivity or premenstrual dysphoric disorder (PMDD) and affects about one in twenty women.

Also, see Top 6 natural treatments for premenstrual mood symptoms.

Contraceptive progestin drugs are bad for mood

Progestins are not the same as the body’s own progesterone, so should not come into this conversation. Unfortunately, many doctors, journalists, and even scientists confuse progestins with progesterone and 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. Progesterone’s calming neurosteroid effect is why progesterone capsules are usually sedating and why women can feel drowsy during times of high progesterone, such as the early luteal phase and pregnancy. Progestins do not convert to allopregnanolone, so progestins cannot soothe mood like progesterone can.

For women with PMDD, allopregnanolone does not calm GABA receptors but instead can stimulate them in a way that produces anxiety and other negative mood symptoms. It’s not that women with PMDD have more allopregnanolone; in fact, they may have less. Instead, their GABA receptors seem to have an abnormal response to allopregnanolone.

GABA receptor PMDD
A GABA receptor with its five subunits, and showing where GABA and neurosteroids bind.

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.

Another factor is the finding that progesterone can cause intestinal permeability, leading to high LPS endotoxin and negative mood symptoms in the luteal phase. According to the research, women are more at risk of this endotoxin effect if they have an underlying problem with chronic progesterone deficiency and high estrogen. 

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:

How to take progesterone for premenstrual mood symptoms

The better approach is to stabilize GABA receptors and, therefore, be able to tolerate the normal ups and downs of progesterone.

It’s also possible to take progesterone. For women with mild premenstrual symptoms (PMS instead of PMDD), low-dose progesterone (such as progesterone cream) can relieve premenstrual mood symptoms by relieving the “progesterone withdrawal” or “GABAergic withdrawal” that occurs at the end of the cycle

For women with neurosteroid change sensitivity and PMDD, a higher dose of progesterone (200 mg) can work better than a lower dose. That’s because of the bimodal association between serum allopregnanolone and adverse mood, which found that in women with PMDD, normal endogenous levels of progesterone are the worst for mood, but above endogenous levels (such as 200 mg) may be better. Very high doses above 400 mg are likely to cause depression in anyone, and unfortunately, the few studies of progesterone for premenstrual mood all used very high doses of 400 to 1200 mg

Natural treatment of PMDD

As I discuss in my summary blog post and podcast/YouTube video about premenstrual mood symptoms, other treatment strategies include:

👉 Tip: For many of my patients, avoiding cow’s dairy is the fastest way to reduce a mast cell or histamine reaction. Avoiding A1casein (and its inflammatory opioid peptide BCM7) can also improve levels of GABA.

👉 Tip: The therapeutic dose is 300 mg of elemental magnesium, so read the label carefully. Most magnesium capsules contain 100 mg.

👉 Tip: I get the best results with magnesium, vitamin B6, and the amino acid taurine (because taurine calms GABA receptors).

Dr Lara Briden
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