Each year in the United States, the menopause transition is experienced by 1.5 million women.  With this change in the hormonal milieu comes troublesome symptoms, including vasomotor symptoms, decreased libido, insomnia, changes in mood, fatigue, and changes in cognitive functioning.  

Fatigue is a common problem among middle-aged women; however, it has received less attention in terms of its treatment.    

Because sleep disturbance is such a common issue in perimenopausal women, the first approach to managing fatigue is assessing for and addressing sleep problems.  There are a variety of options for managing sleep disruption in midlife women, including cognitive behavioral therapy, gabapentin (Neurontin), benzodiazepines, and sedative-hypnotic agents.

Fatigue may also be a symptom of depressive and/or anxiety disorders.  With regard to pharmacologic treatment of these symptoms, selective serotonin and serotonin -norepinephrine reuptake inhibitors are typically used because they can ameliorate  vasomotor symptoms, as well as depression and anxiety.

There are, however, women who will continue to experience significant fatigue in the absence of or despite treatment for depression, anxiety, and/or sleep disturbance.  One of our readers asks about the use of modafinil (Provigil) in this setting. Modafinil has been approved by the FDA for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness due to obstructive sleep apnea but has also been used to treat ADHD and depressive symptoms.  

To my knowledge, no studies have addressed the use of modafinil in perimenopausal or menopausal women.  However, we do have one study, looking at the use of armodafinil (marketed as Nuvigil) in this population, a compound which is closely related to modafinil.  

In this study, women (aged 40-65 years) with menopause-related fatigue received open-label armodafinil therapy (up to 150 mg/day) for 4 weeks.  Symptoms were assessed using the Brief Fatigue Inventory score and Menopause-Specific Quality of Life (MENQOL). The results of this open-label trial provide preliminary evidence that armodafinil may improve menopause-related fatigue and quality of life and other menopausal symptoms, including hot flashes, insomnia, mood, and perceived executive functioning.  (No benefit was seen for anxiety or pain.)

While armodafinil and modafinil are not identical, they are structurally and functionally similar.  Given the promising results, and the fact that modafinil has been used successfully to treat fatigue associated with other medical illnesses, including obstructive sleep apnea, multiple sclerosis, and stroke, suggests that menopausal women with fatigue may also benefit from treatment with modafinil.  

Women and their health care providers must recognize that menopausal symptoms are not simply a nuisance and, therefore, something to be endured. Given the tremendous impact menopausal symptoms may have on women’s quality of life and their ability to function effectively, it is imperative that we find treatments that are safe and effective for managing the array of symptoms women may experience as they transition to the menopause.

Ruta Nonacs, MD PhD

Meyer F, Freeman MP, Petrillo L, Barsky M, Galvan T, Kim S, Cohen L, Joffe H.  Armodafinil for fatigue associated with menopause: an open-label trial.  Menopause. 2015 Jun 29. [Epub ahead of print]

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