Managing Menopause, Part 1: Vasomotor Symptoms

May 22, 2014
Adelaide G. Nardone, MD, FACOG

Menopause symptoms can make some women miserable, sometimes for months or even years at a time. This article discusses vasomotor symptoms and the available options for treatment.

The cessation of women’s monthly estrus cycle is often wrought with much anticipation, agitation, and even anxiety. Menopause is the absence of menstruation for a full year from the last menstrual period, a definition that has been consistent for decades. Physiologically, the transition takes years, during which time there is a diminution of ovarian function, its production of estrogen and progesterone and, ultimately, the end of ovulation.

In the United States, the average age of menopause is 51.3 years, and 11 million women reach natural menopause each year.1 More than 85% of these women experience symptoms associated with estrogen deficiency related to menopause. The most common symptoms are vasomotor symptoms and vaginal dryness. Vasomotor symptoms are usually described as night sweats, hot flashes, and flushes. Vulvovaginal atrophy, often called vaginal dryness, is related to decreased estrogen associated with menopause, and it’s the most common cause of dyspareunia in menopausal and postmenopausal women. 

Risk Factors for Vasomotor Symptoms

- African American ethnicity

- Obesity (adipose tissue is thermogenic)

- Smoking

- Depression/anxiety

- Low socioeconomic status

In this 2-part series on menopause, vasomotor symptoms will be discussed here in part 1, and part 2, which will be featured in 2 weeks, will focus on vulvovaginal atrophy.

Vasomotor Symptoms

Vasomotor symptoms are the most commonly reported menopausal symptoms. These symptoms, often called hot flashes, are characterized by a sudden increase of blood flow, often to the face, neck, and chest, that causes the sensation of extreme heat and profuse sweating.1 When symptoms occur at night they are called “night sweats” and can cause significant sleep disturbances. Episodes of vasomotor symptoms can last 1 to 5 minutes and can be associated with perspiration, flushing, chills, anxiety, and even heart palpitations.

While vasomotor symptoms vary greatly in their intensity and frequency among menopausal women, these symptoms typically are most debilitating during the first one to two years of menopause. For some women, however, they may persist indefinitely.

There also may be ethnic and genetic predispositions for vasomotor symptoms, since up to 20% of women do not experience them. According to the results of the SWAN study (Study of Women’s Health Across the Nation), which assessed menopausal symptoms in 14,906 women with diverse ethnic backgrounds aged 40 to 55 years in the United States, African American women are most likely to report having vasomotor symptoms, and Asian women (Japanese and Chinese) are the least likely to report symptoms.2

Other risk factors for VMS include obesity (adipose tissue is thermogenic), smoking, depression/anxiety, and low socioeconomic status.

In addition, there is neurotransmitter involvement in the genesis of vasomotor symptoms, and therapies have been fashioned around this understanding. One example of this is the recent FDA approval of the SSRI paroxetine capsules (Brisdelle), indicated for moderate to severe vasomotor symptoms associated with menopause. This drug does come with a black box warning for suicidal thoughts and behaviors, as does other SSRI antidepressants.

Management

As clinicians treating these women, we’ve heard the complaints. Our patients describe feeling either hot or cold. At night, they can’t sleep because they find themselves sweating and then taking the covers off, only to wake up cold and shivering. Understandably, they want our advice and ask what they can do to alleviate these symptoms.

The exact physiology of vasomotor symptoms continues to elude us, although there is good data to support that the “thermoregulatory zone” is narrowed for menopausal women. Because vasomotor symptoms parallel what physiological studies confirm-that the fluctuations in core body temperature are more pronounced in postmenopausal women-adding back estrogen does re-widen the thermoregulatory zone.

By far, systemic hormone replacement therapy (HRT) with estrogen alone or in combination with progestin is the most effective therapy for vasomotor symptoms. A meta-analysis of 24 randomized controlled trials (RCT) with 3,329 participants found a 75% reduction in weekly hot flashes frequency in users of oral estrogen or estrogen+progestin compared with placebo.3

As women’s health care providers, most of us understand the effectiveness of estrogen for symptom alleviation in these women. What becomes perplexing is which route, dose, and duration to prescribe. We have an array of estrogen preparations to choose from, including pills, patches, gels, sprays, as well intranasal and buccal systems (Table).

TreatmentDosage/RegimenEvidence of BenefitsFDA Approved

Hormonal

Standard dose

Conjugated estrogen 0.625 mg/dYesYes
 Micronized estradiol-17β 1 mg/dYesYes
 Transdermal estradiol-17β 0.0375–0.05 mg/dYesYes

Low dose

Conjugated estrogen 0.3–0.45 mg/dYesYes
 Micronized estradiol-17β 0.5 mg/dYesYes
 Transdermal estradiol-17β 0.025 mg/dYesYes

Ultra-Low Dose

Micronized estradiol-17β 0.25 mg/dMixedNo
 Transdermal estradiol-17β 0.014 mg/dMixedNo
Estrogen + estrogen agonist/antagonistConjugated estrogen 0.45 mg/d and bazedoxifene 20 mg/dYesYes
ProgestinDepot medroxyprogesterone acetateYesNo
Testosterone No No
Tibolone2.5 mg/dYesNo
Compounded bioidentical hormones NoNo

Nonhormonal

SSRIs and SSNRIs NoNo
Paroxetine7.5 mg/dYesYes
Clonidine0.1 mg/dYesNo
Gabapentin600–900 mg/dYesNo

There is good evidence that oral and transdermal low-dose estrogen regimens effectively alleviate vasomotor symptoms. However, the extent of symptom improvement with low-dose and ultra–low-dose preparations is not yet well understood, although response to any HRT is variable.1

The major risks of combined HRT are thrombosis and breast cancer. (Note: Endometrial cancer is a risk of unopposed estrogen for women with uteri.) Most trials assessing the safety of HRT have studied equine estrogen and medroxyprogesterone acetate. The findings from the Women’s Health Initiative (WHI), which studied a large cohort of healthy menopausal women aged 50 to 77 years, indicated a slightly increased risk of breast cancer, cardiovascular disease, stroke, and venous thromboembolism (VTE) and a decreased risk of fracture and colon cancer after 5 years of combined HRT.4 Estrogen alone was associated with an increased risk of VTE only. Despite these risk associations, this data should not discourage us from recommending HRT to the appropriate patient, and even ACOG is on board with that thought.

“It is difficult to generalize these findings to younger women who are recently menopausal because the WHI was assessing HT for primary CHD prevention in women, many of whom were past the menopause transition,” responded ACOG to the WHI results.1

Given the variable response to HRT and the associated risks, it is recommended that health care providers individualize care and treat women with the lowest effective dose for the shortest duration that is needed to relieve vasomotor symptoms.1 This makes good clinical sense, and we should encourage our patients to adhere to such a regimen.

Last but not least, we should stress the importance of simple lifestyle modification as adjuncts to symptom control, including the following:

- Regular rigorous exercise.

- Healthy and calorie-appropriate diet.

- Limited alcohol intake.

- Wearing layered breathable clothing.

- Stress reduction techniques, such as deep breathing, personal time, and yoga.

References:

1. ACOG practice bulletin no. 141: management of menopausal symptoms. Obstet Gynecol. 2014;123:202-216.

2. Thurston RC, Joffe H. Vasomotor symptoms and menopause: findings from the Study of Women’s Health Across the Nation. Obstet Gynecol Clin North Am. 2011;38:489-501.

3. MacLennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and combined oestrogen/progestogen therapy versus placebo for hot flushes. Cochrane Database System Rev. 2004;4:CD002978. DOI: 10.1002/14651858.CD002978.pub2.

4. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial. Writing Group for the Women’s Health Initiative Investigators. JAMA. 2002;288:321-333.