Is there evidence to support the use of progesterone or hormone replacement therapy (HRT) for generalized anxiety disorder (GAD) and/or panic disorder?

From the Guidelines

There is limited data supporting the use of progesterone or other hormone replacement therapy (HRT) for generalized anxiety disorder (GAD) and panic disorder, and it should not be considered first-line treatment for these conditions. Some studies suggest that progesterone may have anxiolytic effects, particularly in women experiencing hormonal fluctuations such as during perimenopause or the luteal phase of the menstrual cycle 1. Natural progesterone (typically 100-200mg daily) appears to have more calming effects than synthetic progestins. For perimenopausal women with anxiety, a combination of estrogen (such as transdermal estradiol 0.05mg) with progesterone (100-200mg) may be more effective than progesterone alone. However, the evidence for this is largely based on studies in transgender individuals, where hormone therapy has been shown to improve mental health outcomes, including anxiety and depression 1.

The mechanism of progesterone's anxiolytic effects may involve progesterone metabolites like allopregnanolone that enhance GABA activity in the brain, producing calming effects similar to benzodiazepines. Before considering hormonal treatments, patients should undergo thorough evaluation to rule out other causes of anxiety and should discuss the potential cardiovascular, breast cancer, and thrombotic risks associated with HRT. Standard anxiety treatments including SSRIs, SNRIs, psychotherapy, and lifestyle modifications remain the established first-line approaches, as supported by guidelines for social anxiety disorder 1 and anxiety in cancer survivors 1.

Key points to consider:

• HRT should not be considered first-line treatment for anxiety disorders
• Progesterone may have anxiolytic effects in women with hormonal fluctuations
• Natural progesterone may be more effective than synthetic progestins
• Combination of estrogen and progesterone may be more effective than progesterone alone
• Patients should undergo thorough evaluation and discuss potential risks before considering HRT for anxiety.

From the Research

Treatment Options for GAD and Panic Disorder

There are various treatment options available for Generalized Anxiety Disorder (GAD) and Panic Disorder, including:

• Cognitive behavior therapy
• Anti-depressants, such as selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors 2, 3, 4, 5, 6
• Benzodiazepines, although their use is limited due to potential for abuse and lack of antidepressant properties 3, 4, 5
• Other treatment options, such as pregabalin, tricyclic antidepressants, buspirone, and moclobemide 3, 4, 5

Hormone Replacement Therapy (HRT) and Progesterone

There is no consistent evidence to support the use of progesterone or other HRT for GAD and/or panic disorder in the provided studies 2, 3, 4, 5, 6. The studies primarily focus on the effectiveness of anti-depressants, benzodiazepines, and other pharmacological treatments for anxiety disorders.

Key Findings

• Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors are commonly recommended as first-line treatments for GAD and panic disorder 2, 3, 4, 5, 6
• Benzodiazepines may be considered as a possible first-line therapy in eligible patients, but their use is limited due to potential for abuse and lack of antidepressant properties 3, 4, 5
• Novel treatment strategies, such as medications that act on GABA, glutamate, and other neurotransmitter systems, are being explored 4