Non-Hormonal Treatments For Hot Flashes

By: Lauren Weber, DO • Posted on August 16, 2012 • Updated March 09, 2021

Menopause

Menopause is defined by the cessation of ovulation and menstruation, 12 months of amenorrhea (the absence of a menstrual period in a woman of reproductive age) is characteristic of menopause. This marks the end of reproductive capabilities of the female. Follicle-stimulating hormone (FSH) is elevated and estrogen level decreases, which can lead to symptoms such as:

• Hot flashes
• Night sweats
• Irritability
• Difficulty concentrating
• Vaginal dryness
• Painful intercourse
• Urinary tract infections
• Difficulty sleeping
• Body aches or itching

Menopause and Osteoporosis

The loss of estrogen places women at risk for osteoporosis, hair loss and heart disease (especially after age 65). Bone loss begins to accelerate approximately two to three years before the last menstruation cycle. For an interval of a few years around menopause, women lose two percent of bone annually. Afterward, bone loss slows to about one to one and half percent per year (4). The National Osteoporosis Foundation states that in the five to seven years after menopause, a woman can lose up to 20 percent or more of their bone density. Loss of teeth is a risk as well, especially as bone mineral density decreases.

Menopause can happen naturally, surgically, or iatrogenically (because of chemotherapy or radiation therapy). Every woman varies in her journey through menopause. Women that go through menopause due to surgical intervention have had a hysterectomy with bilateral oophorectomy or just a hysterectomy. There are some women who go into menopause even though their ovaries remain in place. Women who have surgical menopause supposedly have much worse vasomotor symptoms (VMS) than women who go through menopause naturally. Iatrogenic causes of menopause include medications, chemotherapy, or radiation therapy.

Vasomotor Symptoms (VMS) During Menopause

VMS symptoms are the main reason why women seek out medical attention (2). They occur in more than 75% of postmenopausal women (1). Those symptoms include:

• Hot flashes
• Dry skin
• Formication
• Sleep issues

Hot flashes typically last between 1-5 minutes. The hot flash is described as a hot sensation that radiates through the body, particularly the upper body. There is an increase in heart rate, sweating, and peripheral vasodilatation (flushing). Hot flash frequency increases during peri-menopause and continues for an unknown length of time.

Every woman's menopausal symptoms are different. Some women have night sweats, which are hot flashes that occur while sleeping and can be disruptive to sleep and not to mention the need to get up and change clothes or sheets. Most of the complaints I get in the office are women complaining that they soak their clothes or can’t seem to get their room to the right temperature because they are either burning up or freezing. There are a few theories surrounding the causes of hot flashes:

1. One of the theories suggests that hot flashes are preceded by a very small increase in core body temperature, which may trigger the hot flash (5-6).
2. There is increasing evidence that both norepinephrine and serotonin (5-HT) are associated with the communication and modulation of the temperature homeostasis maintained by the hypothalamus (9).

Data from the Study of Women’s Health Across the Nation, which surveyed US women of different ethnic backgrounds showed that the prevalence of VMS was highest among African-American and Hispanic women and lowest for women of Asian (Chinese and Japanese) ancestry, while Caucasian were in between.

Higher body mass index (heavier women), premenstrual symptoms, perceived stress, and age were also significantly associated with vasomotor symptoms. In the SWAN study both passive and active smoke exposure were studied, only passive but not active smoke exposure remained significantly associated with vasomotor symptoms (8). Smokers typically go into menopause 2-3 years earlier than non-smokers.

Choosing the Right Treatment for Menopause Symptoms

Choosing the right treatment for a woman to help control her symptoms should be individualized. Not all women have the same symptoms and therefore, not all need the same treatment.

Estrogen Therapy

The gold standard treatment for hot flashes and prevention of osteoporosis is estrogen therapy, but for those that are unable to take estrogen (breast cancer patients or those with previous blood clots while on hormones) or are unwilling to take estrogen, it is nice to have various ways to treat the hot flashes, night sweats, and vaginal atrophy (that causes painful intercourse and could increase risk for urinary tract infections).

The FDA approved, for the first time, a medication for the treatment of moderate to severe hot flashes called low-dose paroxetine (Brisdelle) (7.5 mg/day). Brisdelle should be used with caution (or not used at all) with breast cancer treatment, tamoxifen, as it can decrease its effectiveness.

Alternative therapies for VMS symptoms

For women who are unable to take hormone therapy or are unwilling to take hormone therapy and those that suffer from depression as well, the option of using antidepressants would be a good choice to help control their symptoms of not only VMS but for their mood as well. There have been a number of studies that have shown that serotonin-norepinephrine reuptake inhibitors (SNRIs) and selective serotonin reuptake inhibitors (SSRIs) are efficacious in the treatment of VMS in non-depressed women (10). Placebo-controlled clinical trials have suggested that agents from the SSRI and SNRI family reduce hot flashes by 50-60 percent (13).

Off label and not FDA approved for VMS

• SNRIs - inhibits the uptake of both 5-HT, NE, and dopamine activities
  • Venlafaxine (Effexor) (37.5-75mg/day)
  • Desvenlafaxine (Pristiq) (50mg/day)
  • Duloxetine (Cymbalta) (60-120mg/day)
• SSRIs – inhibits the uptake of 5-HT, and minimal uptake of NE and dopamine
  • Fluoxetine (Prozac, Sarafem) (20mg/day)
  • Paroxetine (Paxil) (12.5-50mg/day)
  • Citalopram (Celexa) (20mg/day)
  • Sertraline (Zoloft) (50-100mg/day)

One study reported that venlafaxine and paroxetine appeared to be more effective than sertraline and fluoxetine (11).

Beware of using tamoxifen and SSRIs. They are both metabolized by CYP2D6, which can possibly reduce the levels of tamoxifen, paroxetine (Paxil) showed the greatest effect on reduction of tamoxifen metabolites (7). Venlafaxine appears to have minimal impact on tamoxifen metabolism (12).

Gabapentin (Neurontin)

Gabapentin is an FDA approved medication for partial seizures and postherpetic neuralgia. The mechanism of action of how it helps with VMS is unclear but has been shown to be effective at treating VMS in studies. Therapy is typically started at night as a side effect of the medication is drowsiness. The medication has a half-life of 5-7 hours, so for those patients who have more hot flashes at night, this would be a great option for them. The medication is typically started at a dose of 300mg QHS and may be increased to three times a day. Gabapentin has no known positive or negative effect on the bone, breast, or endometrial tissue, and has no impact on vaginal atrophy.

Clonidine

Clonidine stimulates alpha 2 adrenergic receptors in the brain resulting in reduced blood pressure. It may be used for the treatment of mild VMS especially in someone that has hypertension. Clonidine has no known positive or negative effect on the bone, breast, or endometrial tissue, and no impact on vaginal atrophy (2). Side effects of this medication include drowsiness, constipation, and insomnia. The initial dose of therapy is 0.05 mg BID and may be increased to 0.1 mg BID. A word of caution, when discontinuing this medication you need to taper off other wise you might get rebound hypertension, headache, and/or agitation.

Herbals and neutraceuticals

Herbals and neutraceuticals are not controlled or monitored by the FDA. While many patients feel that these are safer because they are “natural” they need to be aware that there is no way to know exactly what is in the pill that they are taking. Unfortunately soy has shown to increase hot flashes over placebo.

Lifestyle modifications to help manage VMS

Regular exercise can help with mental clarity, depression, maintaining a healthy BMI as well as improve sleep quality, which can help decrease your VMS symptoms. Dressing in layers during the day, wearing clothing that wicks sweat away while sleeping, and even using a fan or sleeping on a chill pillow at night can help with VMS. Smokers typically have worse hot flashes plus it is hard on their bones. Tobacco is toxic to your bones and ages your skin!

Addendum

November 1, 2013: FDA approves first non-hormonal treatment, Brisdelle (low dose paroxetine 7.5mg daily at bedtime), for hot flashes associated with menopause. Read more.

Be Strong. Be Healthy. Be in Charge!

- Lauren Weber, DO

References:

1. Pachman D, Jones J, Loprinzi, C. Management of menopause-associated vasomotor symptoms: Current treatment options, challenges and future directions. International Journal of Women’s Health 2010:2, pp:123-135.
2. Thacker H. Assessing Risks and Benefits of Nonhormonal Treatments for Vasomotor Symptoms in Perimenopausal and Postmenopausal Women. Journal of Women’s Health. Volume 20, Number 7, 2011. pp: 1007-1016.
3. Jenkins M, Sikon A. Update on nonhormonal approaches to menopausal management. Cleveland Clinic Journal of Medicine. Volume 75, Supplement 4, May 2008. pp: S17-S24.
4. NAMS continuing medical education activity Management of osteoporosis in postmenopausal women: 2010 position statement of The North American Menopause Society. Menopause: The Journal of The North American Menopause Society. Vol. 17, No. 1, pp. 23/24.
5. Freedman RR, Blacker CM. Estrogen raises the sweating threshold in symptomatic but not in asymptomatic post-menopausal women. Fertile Sterile. 2000;74:20-23.
6. Freedman RR, Blacker CM. Estrogen raises the sweating threshold in postmenopausal women with hot flashes. Fertil Steril. 2002;77:487-490.
7. Stearns V, Johnson MD, Rae JM, et al. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. Journal of National Cancer Institute. 2003;95:1758-1764.
8. Gold EB, Block G, Crawford S et al. Lifestyle and demographic factors in relation to vasomotor symptoms: baseline results from the Study of Women’s Health Across the Nation. Am J Epidemiol 2004; 159: 1189–99.
9. Lilue M, Palacios S. Non-hormonal treatment for vasomotor symptoms during menopause: role of desvenlafaxine. Ginecol Obstet Mex. 2009 Oct;77(10):475-81.
10. Hall E, Frey B, Soares C. Non-Hormonal Treatment Strategies for Vasomotor Symptoms: A Critical Review. Drugs. 2011 Feb 12;71(3):287-304.
11. Nelson HD, Vesco KK, Haney E, et al. Nonhormonal therapies for menopausal hot flashes: Systematic review and meta-analysis. JAMA. 2006;295:2057–2071.
12. Jin Y, Desta Z, Stearns V, et al. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst. 2005;97:30–39.
13. Stearns V. Serotonergic agents as an alternative to hormonal therapy for the treatment of menopausal vasomotor symptoms. Treat Endocrinol. 2006;5(2):83-7.

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