Menopause is the natural cessation of menstrual periods, defined as 12 months of amenorrhea without other pathologic or physiologic explanation. This event marks the complete or near complete loss of functional ovarian follicles leading to decreased estrogen production and elevated follicle stimulating hormone (FSH) concentrations. The mean age of menopause in US females is currently 51. The years leading up to this state are called perimenopause and last, on average, 4 years. During this time multiple endocrine system alterations occur and periods become less regular. Women may experience hot flashes, vaginal changes, and sleep and mood disturbances. When these changes occur before age 40, the condition is called premature ovarian failure.
It is the decrease in circulating estrogen that results in the clinical symptoms of menopause. Hot flashes are the most common initial symptom, occurring in up to 80% of women in some ethnic groups in the US. This phenomenon is due to estrogen withdrawal and consequent bursts of gonadotropin-releasing hormone from the hypothalamus, which alter thermoregulatory function. It is important to educate patients that hot flashes can begin years before the last menstrual period and last many years after the last menstrual period. A hot flash is a sensation of heat and perspiration that may last several minutes, often preceded or followed by chills and shivering. In some cases, palpitations with or without anxiety accompany these symptoms. Hot flashes are more common at night and often cause disruptions in sleep. Anxiety and depression are common during this time and aggravate sleep disturbances. Vaginal dryness, due to the decrease in estrogen stimulation of the vagina and urethra, is common and may cause dryness, itching, and dyspareunia.
Other findings that occur as a result (or are believed to be a result) of decreasing estrogen include:
- Increased rate of bone loss
- Increased cardiovascular disease risk
- Memory changes
- Body composition changes
- Impaired balance
African American women report more frequent hot flashes compared with whites. Symptoms appear to be significantly less common in Asia, compared with North America, a difference that is likely attributed to lifestyle factors, especially diet.
Risk factors that predict severity of menopausal symptoms include smoking, lower socioeconomic status, low calcium intake, and BMI, with higher BMIs correlating with more severe symptoms.
In women over age 45 who present with changes in menstrual intervals, with or without other menopausal symptoms, the diagnosis of menopausal transition can be made without other laboratory workup. A follicle stimulating hormone (FSH) level can be drawn, but during the early years of menopause these levels fluctuate widely and may be misleading. The possibility of pregnancy should be kept in mind in sexually active women. If symptoms suggest other causes of amenorrhea, such as hyperprolactinemia or hyperthyroidism, the possibility of these conditions should be evaluated with appropriate laboratory testing.
If the menopausal status is in doubt (e.g., in a woman under 45 with amenorrhea), pregnancy, thyroid disease, and prolactin elevation should be ruled out. Premature ovarian failure should be considered and is suggested by a low serum estradiol level and elevated serum FSH level.
For women at risk for osteoporosis, evaluation with dual-energy x-ray absorptiometry (DEXA) scan may be used to measure bone density. An initial examination at age 65 is reasonable; earlier screening has been suggested for women who smoke or have family histories of early-onset fragility fractures.
Women with risk factors for coronary artery disease should be followed regularly and treated as necessary for prevention, including treatment for hypertension, hyperlipidemia, and other cardiovascular complications (see Cardiovascular section). This and other screening recommendations (e.g., for breast cancer and colon cancer) are related to a woman’s age and not to her menopausal status.
Menopause is a normal part of life, and no treatment is typically required. Symptoms, when they occur, are usually tolerable and eventually pass. However, for women with particularly bothersome symptoms, the following considerations may be helpful.
Since excess weight is associated with worse menopausal vasomotor symptoms, weight loss should be part of any treatment plan for overweight or obese women. Overweight women who successfully lose weight experience less bothersome hot flashes.
Oral hormone therapy is highly effective for menopausal symptoms, but women considering this therapy should be advised that it has been associated with an increased risk of thromboembolic events, breast cancer, and endometrial cancer.
Combined hormonal contraceptives (CHC) may be a treatment option in select perimenopausal women who also need contraception. The Centers for Disease Control and Prevention state that CHC are a category 2 medication, meaning the benefits outweigh the theoretical or proven risks, in the perimenopausal years. Other effective medications for hot flashes include some antidepressant medications (e.g., venlafaxine), clonidine, and gabapentin.
Over-the-counter moisturizers may be used for vaginal dryness. If vaginal moisturizers are of insufficient benefit, vaginal estrogens may be used (at lower doses than for oral therapy). The vehicle for disbursement (e.g., cream, ring, pessary, tablet) is not important. Systemic symptoms are generally not improved by local therapy, but systemic side effects also rarely occur.
Nutritional therapies may be useful (see Nutritional Considerations).
While calcium plays important physiologic roles in the body, new evidence suggests that increasing calcium intake, through diet or supplementation, does not significantly increase bone mineral density or decrease risk of fracture. , Adequate exposure to vitamin D, either via dietary sources, supplements, or sun exposure, is beneficial for fracture prevention.
Exercise has not been consistently correlated with reduced intensity or frequency vasomotor symptoms. However, regular exercise is associated with improved quality of life in menopausal women. Exercise is also important for stimulating bone formation and decreasing resorption, as well as for cardiovascular health.
Antiresorptive medications, such as bisphosphonates, can be considered for patients with low bone-mineral density. These medications are now preferred over estrogen for prevention and treatment of postmenopausal fractures. This class of medications does come with rare but serious side effects, including osteonecrosis of the jaw, esophageal ulcers, and chronic musculoskeletal pain.
Cognitive behavioral therapy has been shown to reduce frequency of vasomotor symptoms.
Relaxation and other stress management techniques have been recommended by some, with the theoretical basis that norepinephrine release plays a role in hot flashes; these techniques reduce central nervous system adrenergic tone. However, a recent systematic review concluded that there is lack of good data to suggest that relaxation techniques, including paced respiration, provide significant relief.
Data regarding benefits of acupuncture for treatment of menopausal symptoms are conflicting.
The loss of estrogen that is responsible for menopausal symptoms also affects the risk for certain lifestyle-related diseases (e.g., cardiovascular disease) that are affected by diet as well. Women who experience more severe vasomotor symptoms weigh significantly more and have significantly higher blood pressure and cholesterol levels, a greater extent of aortic calcification and carotid intima media thickness, and poorer endothelial function, compared with women with less pronounced symptoms. , Current evidence indicates the following changes in diet or supplementation with botanical products may be helpful for treating menopausal symptoms or the metabolic consequences of a loss of estrogen.
Follow a diet that promotes attainment and maintenance of a healthy weight. In a study of more than 17,000 women with baseline vasomotor symptoms, those who lost more than 10 lbs or 10% or more of their baseline weight were significantly more likely to experience elimination of these symptoms compared with women who did not lose weight. Some evidence suggests that a low-fat diet may be especially helpful. In an observational study, perimenopausal women following low-fat (~ 20%) diets scored significantly lower on the vasomotor symptoms subscale (including hot flashes and night sweats), compared with a control group following a diet containing ~ 30% fat. These women also had reductions in serum cholesterol, estrogen levels, and mammographic densities. A beneficial effect of a low-fat diet on menopausal symptoms has not been established in controlled clinical trials.
Consider a plant-based diet that includes whole soy foods. Plant-based diets can help with loss of excess weight, as well as reduction of blood lipids, blood pressure, insulin resistance and inflammation, and have been associated with a lower risk for experiencing menopausal symptoms. Soy products should be included due to their cardiovascular benefits and potential efficacy for treating certain menopausal symptoms. A meta-analysis of controlled clinical trials in non-Asian women supplemented with soy isoflavones found significant reductions in body weight, fasting glucose, and fasting insulin when compared with placebo.
Asian women who frequently include soy products in their diets have a much lower prevalence of menopausal symptoms compared with their Western counterparts, which has lead to the speculation that phytoestrogens in soy (isoflavones) may be acting as estrogens. However, Asian diets and lifestyles vary from Western diets in many other respects (e.g., less intake of meat and dairy products, much lower fat intake, and greater intake of grains and vegetables), making it difficult to attribute this difference to soy. A systematic review revealed that only a minority of clinical trials using soy isoflavones provided relief from hot flashes, and another review found this reduction to be only 21% in severity and 26% in frequency. The amount of genistein (a main soy isoflavone) appeared as a critical variable in these results. A number of meta-analytic reviews have examined the effect of soy isoflavones on the Kupperman Index (KI, a comprehensive grouping of eleven menopausal symptoms) with null results.
Botanical supplements may provide some benefit. These include red clover ( Trifolium pretense), Black cohosh ( Cimicifuga racemosa), dong quai ( Angelica sinensis), and Chaste tree ( Vitex agnus castus) and are discussed below.
Red clover contains isoflavones similar to those found in soy foods, and studies in postmenopausal women have found increases in high-density lipoprotein (HDL), arterial compliance, bone density, and cognitive function. 22 The weight of evidence on Black cohosh indicates that its effects mainly address the neurovegetative and emotional symptoms of menopause, rather than vasomotor symptoms. 2 3 It may be helpful for treating these symptoms, provided formulations of this herb contain biologically relevant amounts of the active compounds. 25 Dong quai and Chaste tree have been found to result in significant decreases in the Kupperman Menopause Index. These are thought to be the result of binding with estrogen receptors and dopaminergic effects. 26
What to Tell the Family
It is useful for the patient and family to understand that menopause is a normal condition, not a disease or diagnosis. It can, however, be accompanied by symptoms and, in some cases, mood changes, all of which decrease over time. Diet changes and other lifestyle modifications may reduce vasomotor symptoms, in addition to their other benefits.
- Gold EB et al: Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women's health across the nation. Am J Public Health 96:1226, 2006 [PMID:16735636]
- Pérez JA et al: Epidemiology of risk factors and symptoms associated with menopause in Spanish women. Maturitas 62:30, 2009 [PMID:19010615]
- Huang AJ et al: An intensive behavioral weight loss intervention and hot flushes in women. Arch Intern Med 170:1161, 2010 [PMID:20625026]
- Centers for Disease Control and Prevention (CDC). U.S. medical eligibility criteria for contraceptive use, 2010. MMWR Recomm Rep . 2010;59:1-86.
- Bolland MJ, Leung W, Tai V, et al. Calcium intake and risk of fracture: systematic review. BMJ . 2015;351-365.
- Tai V, Leung W, Grey A, Reid IR, Bolland MJ. Calcium intake and bone mineral density: systematic review and meta-analysis. BMJ . 2015;351-365.
- Pludowski P et al: Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality-a review of recent evidence. Autoimmun Rev 12:976, 2013 [PMID:23542507]
- Daley A et al: Exercise for vasomotor menopausal symptoms. Cochrane Database Syst Rev Nov 28 [PMID:25431132]
- Daley A et al: Exercise participation, body mass index, and health-related quality of life in women of menopausal age. Br J Gen Pract 57:130, 2007 [PMID:17266830]
- Ayers B et al: Effectiveness of group and self-help cognitive behavior therapy in reducing problematic menopausal hot flushes and night sweats (MENOS 2): a randomized controlled trial. Menopause 19:749, 2012 [PMID:22336748]
- Shanafelt TD et al: Pathophysiology and treatment of hot flashes. Mayo Clin Proc 77:1207, 2002 [PMID:12440557]
- Saensak S et al: Relaxation for perimenopausal and postmenopausal symptoms. Cochrane Database Syst Rev Jul 20 [PMID:25039019]
- Dodin S et al: Acupuncture for menopausal hot flushes. Cochrane Database Syst Rev 7:, 2013 [PMID:23897589]
- Franco OH et al: Vasomotor symptoms in women and cardiovascular risk markers: Systematic review and meta-analysis. Maturitas 81:353, 2015 [PMID:26022385]
- Thurston RC, Joffe H: Vasomotor symptoms and menopause: findings from the Study of Women's Health across the Nation. Obstet Gynecol Clin North Am 38:489, 2011 [PMID:21961716]
- Kroenke CH et al: Effects of a dietary intervention and weight change on vasomotor symptoms in the Women's Health Initiative. Menopause 19:980, 2012 [PMID:22781782]
- Liu ZM et al: Whole plant foods intake is associated with fewer menopausal symptoms in Chinese postmenopausal women with prehypertension or untreated hypertension. Menopause 22:496, 2015 [PMID:25387345]
- Zhang YB, Chen WH, Guo JJ, et al. Soy isoflavone supplementation could reduce body weight and improve glucose metabolism in non-Asian postmenopausal women—a a meta-analysis. Nutrition . 2013;29:8-14. 18. Chen MN, Lin CC, Liu CF. Efficacy of phytoestrogens for menopausal symptoms: a meta-analysis and systematic review. Climacteric . 2015;18:260-269. 19 . Ghazanfarpour M, Sadeghi R, Roudsari RL, Khorsand I, Khadivzadeh T, Muoio B. Red clover for treatment of hot flashes and menopausal symptoms: a systematic review and meta-analysis. J Obstet Gynaecol. 2016;36:301-311. 22 . Thomas AJ , Ismail R, Taylor-Swanson L, et al. Effects of isoflavones and amino acid therapies for hot flashes and co-occurring symptoms during the menopausal transition and early postmenopause: a systematic review. Maturitas . 2014 ;78:263-276. 23 . Drewe J, Bucher KA, Zahner C. A systematic review of non-hormonal treatments of vasomotor symptoms in climacteric and cancer patients. Springerplus . 2015;4:65-94. 24 . Beer AM, Osmers R, Schnitker J, Bai W, Mueck AO, Meden H. Efficacy of black cohosh (Cimicifuga racemosa) medicines for treatment of menopausal symptoms - comments on major statements of the Cochrane Collaboration report 2012 "black cohosh (Cimicifuga spp.) for menopausal symptoms (review)". Gynecol Endocrinol . 2013;29:1022-1025. 25 . Beer AM, Neff A. Differentiated evaluation of extract-specific evidence on Cimicifuga racemosa's efficacy and safety for climacteric complaints. Evid Based Complement Alternat Med . 2013;2013:860602-860623. 26 . De Leo V, Cappelli V, Di Sabatino A, Morgante G. Phyto-oestrogens and chaste tree berry: a new option in the treatment of menopausal disorders. J Women’s Health Care . 2014;3:182-188.