Update on nonhormonal approaches to menopausal management

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The risk-benefit evaluation for managing vasomotor symptoms and other menopause-related health issues should be tailored to each individual woman, taking into account her own assessment of the most bothersome symptom(s) and her personal weighting of risks versus quality of life. For most symptomatic menopausal women, hormone therapy (HT) remains the best treatment, but various nonhormonal options are available for treating menopausal symptoms and bone loss in women who are unable or unwilling to take HT. Low doses of local vaginal estrogen remain an option for treatment of vaginal atrophy in these women. This article reviews alternatives to systemic HT for treating menopausal symptoms and related health issues.



As the life expectancy of women in the United States now exceeds 80 years,1 many millions of US women will spend more than one-third to even one-half of their lives beyond menopause. While hormone therapy (HT) can effectively address many of the symptoms of menopause, women who are unwilling or unable to take HT need nonhormonal alternatives for treatment of menopausal symptoms as well as the estrogen-deficiency bone loss that ensues in many women. This article reviews current and experimental nonhormonal therapies for menopausal symptoms and related issues, such as midlife sexual dysfunction and maintenance of bone health.


We begin the discussion of menopausal health with a clarification of some terms.2

Menopause refers to the final menstrual period and simply represents a point in time. Menopause can be diagnosed only a year after it occurs, when it is clear that the last menstrual period was truly the final one.

Perimenopause consists of three components: the period shortly before menopause (when the biological and clinical features of impending menopause begin), menopause itself (final menstrual period), and the year following menopause. Perimenopause is synonymous with menopausal transition.

Postmenopause is the period beginning at the time of the final menstrual period (menopause), although it is recognized only after a year of amenorrhea. The early postmenopausal phase is the first 5 years after menopause, whereas all the time thereafter is referred to as the late menopausal phase.



The primary symptoms of perimenopause are:

  • Vasomotor symptoms (eg, hot flashes, night sweats)
  • Menstrual cycle changes (ie, oligomenorrhea, amenorrhea)
  • Vaginal dryness.

Secondary symptoms include sleep disturbance, low sex drive and/or reduced sexual arousal, stress or urge urinary incontinence, mood changes, and somatic complaints.

Vasomotor symptoms, vaginal dryness, and dyspareunia (painful intercourse) contributing to sexual dysfunction have been correlated with the loss of sex hormones (particularly estrogen) associated with menopause, whereas the other symptoms listed above (sleep disturbance, urinary symptoms, mood changes, somatic symptoms) have not been linked definitively to menopause and may be a function of aging.2

Vasomotor symptoms are the predominant reason that women seek medical treatment around the time of menopause.3 More than 75% of women report hot flashes within the 2 years surrounding menopause. Among these women who have hot flashes, 25% report that these symptoms remain for greater than 5 years, and 10% report that they remain for more than 10 years.3 Vasomotor symptoms may be associated with sleep disturbance, mood swings, cognitive deficits, social impairment, a reduction in productivity, embarrassment, anxiety, and fatigue.

Individualizing the evaluation is imperative

Figure 1. Key components of the menopausal assessment.
Assessment of symptoms and their impact on quality of life is a key component of the menopausal evaluation (Figure 1). During this visit, the most bothersome symptoms are elicited and the patient’s desire for treatment to relieve symptoms is assessed. The risks and benefits of various treatment options, both hormonal and alternatives to HT, are discussed. The risk-benefit ratio will depend on the inherent risks of each treatment, the individual patient’s risk profile, and the desired outcomes.

The overall patient must be considered in this assessment, which includes her personal history, family history, social history, and current medication use. Common factors affecting postmenopausal health—such as bone density; vaginal, bladder, and sexual function; cardiovascular health (including lipid profile, blood pressure, and tobacco use); thromboembolic risk; and cancer risk, including breast cancer—should be included in the assessment. For most women under the age of 60 years who have menopausal symptoms, HT remains the gold standard and recommended treatment, according to both the American Association of Clinical Endocrinologists4 and the North American Menopause Society.5 However, for women who cannot or will not take HT, there are other treatment options to consider.


Options for the treatment of vasomotor symptoms include lifestyle modification, HT, nonhormonal centrally acting agents, and complementary and alternative medicine. Lifestyle modifications to cope with hot flashes include dressing in layers, adjusting room temperature, and deep breathing and relaxation exercises. Complementary and alternative medical approaches to vasomotor symptoms have generally not been evaluated in well-designed studies or have been found ineffective, so they will not be discussed further here. HT was discussed at length in the previous articles in this supplement, and because of its perceived risks, some women are unwilling to use HT. For these women, and particularly for those with contraindications to HT—especially those with breast cancer treated with medications that promote severe vasomotor symptoms—nonhormonal alternatives for vasomotor symptom treatment clearly are needed. Centrally acting agents show the most promise in this regard.

The rationale for a nonhormonal approach

Development of vasomotor symptoms seems to be related to the withdrawal of gonadotropins and the instability of serotonin and norepinephrine in the hypothalamus.6–9 A small increase in core temperature precedes a vasomotor symptom episode in approximately 70% of women. A narrowing of the hypothalamic thermoregulatory set point is followed by an increasing sensation of intense heat and peripheral vasodilation, leading to an exaggerated response (ie, severe sweating and flashing) to the very small rise in core temperature. This pathophysiology of vasomotor symptoms is the basis for the use of alternatives to HT, such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).

In general, studies of nonhormonal pharmacologic agents are limited by small numbers of patients, short duration of therapy, and high placebo response rates (Table 1). Because of a lack of head-to-head trials, the relative efficacy of nonhormonal therapies cannot be determined at this time. As with HT, a dose-response relationship with respect to efficacy and side effects has been observed with nonhormonal therapies.


Next Article:

Case studies and clinical considerations in menopausal management

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