Can Progesterone Cause Anxiety?

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Reproductive Hormone

  • Progesterone is a hormone important in the regulation of the menstrual cycles of women. Normally progesterone levels rise during the last two weeks of the cycle to stop bleeding and allow the lining of the uterus (endometrium) to rebuild its tissues, so that the woman's ova (eggs) are receptive to the male's sperm cells.

    Progesterone and similar substances (progestogens and progestins) are present in birth control medicines, are used in menopausal hormone replacement therapy and to regulate unusual bleeding in menstruation.

Effects on Mood

  • Progesterone and progestogens increase levels of a brain chemical (monoamine oxydase, or MAO) known to exacerbate depression and irritability in women who already have a tendency toward depression. However, the combination of estrogen and progestogens used in birth control pills and hormone replacement does not seem to affect mood since the substances cancel each other's effects.

    Postmenopausal hormone interventions using different combinations of estrogen and progestogen/progesterone are examined in depth in the PEPI trial covered in the Journal of the American Medical Association.

How It Works

  • A bolus (injection) of progesterone stimulates the amygdala, a region of the brain that controls emotion, according to psychiatric research into the condition known as postmenstrual dysphoric disorder (PMDD). In PMDD, which some women experience anxiety and depression in the week before menstruation.

    Researchers at Radboud University in the Netherlands tested the progesterone-amygdala hypothesis and found that women given a dose of progesterone showed greater activity of the amygdala in MRI scans. The scientists suggest progesterone could also affect other areas of the brain involved in mood regulation.

    It's possible that increased progesterone excites the amygdala at the same time it prevents the prefrontal cortex from regulating that excitement because of altered sensitivity to estrogen, according to the Dutch research team.

    Women with PMDD have a genetic variation that distinguishes them from other women. Researchers at Radboud University speculate that this genetic difference may account for why some have this sensitivity and others do not.

    The U.S. Food and Drug Administration has approved several medications to treat PMDD: the antidepressants Zoloft and Serafem, controlled-release paroxetine Paxil CR and the oral contraceptive Yaz.

Progesterone and Bonding

  • Paradoxically, progesterone also appears to promote feelings of well-being and reduce levels of anxiety and stress. A study at the University of Michigan concluded that social bonding increases levels of progesterone, which also is linked with a desire to help others.

    The Michigan researchers believe progesterone may be related to oxytocin, a hormone instrumental in maternal responsiveness, trust and pair-bonding in humans and other mammals.

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