The American College of

Obstetricians and Gynecologists

WOMEN’S HEALTH CARE PHYSICIANS

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P RACTICE BULLET IN
CLINICAL MANAGEMENT GUIDELINES FOR OBSTETRICIAN – GYNECOLOGISTS

NUMBER 141, JANUARY 2014 (Replaces Practice Bulletin Number 28, June 2001)
(Reaffirmed 2018) (See also Committee Opinion Number 565, Committee Opinion Number 556)

Management of Menopausal Symptoms

Vasomotor and vaginal symptoms are cardinal symptoms of menopause. Vasomotor symptoms can be particu-
larly troubling to women and are the most commonly reported menopausal symptoms, with a reported prevalence
of 50–82% among U.S. women who experience natural menopause (1, 2). The occurrence of vasomotor symptoms
increases during the transition to menopause and peaks approximately 1 year after the final menstrual period (3–5).
The purpose of this document is to provide evidence-based guidelines for the treatment of vasomotor and vaginal
symptoms related to natural and surgical menopause. (Treatment of menopausal symptoms in cancer survivors is
discussed in the American College of Obstetricians and Gynecologists’ Practice Bulletin Number 126, Management
of Gynecologic Issues in Women With Breast Cancer.)

Background and vaginal symptoms are the most closely associated

with the hormonal changes of the menopausal transition
Menopause is the permanent cessation of menstruation (6, 7).
that occurs after the loss of ovarian activity. By defini-
tion, menopause cannot be determined to have occurred Vasomotor Symptoms
until 1 year after the last menstrual period. In North The sudden sensation of extreme heat in the upper body,
America, the median age of menopause is 51 years. Most particularly the face, neck, and chest, is referred to as
women begin to undergo the physiologic changes asso- a hot flush. These episodes, which typically last 1–5
ciated with menopause in the years preceding the final minutes (8), can be characterized by perspiration, flush-
menstrual period. This interval is often referred to as ing, chills, clamminess, anxiety, and, on occasion, heart
perimenopause, the climacteric, or––more recently––the palpitations (9). Vasomotor symptoms may also interfere
menopausal transition (6). with sleep and cause chronic sleep disruption in some
The menopausal transition is marked by fluctua- women (10).
tions in hormone levels as ovarian function begins to Vasomotor symptom episodes vary in frequency and
slow down. Serum levels of estradiol and progester- duration. Studies show that 87% of women who report
one decrease and follicle-stimulating hormone levels hot flushes experience these symptoms on a daily basis,
increase, resulting in physiologic changes and clinical with approximately 33% experiencing more than 10 hot
symptoms. Although women report experiencing a vari- flushes per day. Published reports also indicate that
ety of menopausal symptoms, vasomotor (hot flushes) symptoms may persist longer than the previous estimate

Committee on Practice Bulletins—Gynecology. This Practice Bulletin was developed by the Committee on Practice Bulletins—Gynecology with the
assistance of Clarisa Gracia, MD. The information is designed to aid practitioners in making decisions about appropriate obstetric and gynecologic care.
These guidelines should not be construed as dictating an exclusive course of treatment or procedure. Variations in practice may be warranted based on the
needs of the individual patient, resources, and limitations unique to the institution or type of practice.
of 6 months to 2 years, although the overall duration variations are due to differing cross-cultural perceptions
of hot flushes remains unclear (5). Median durations of and reporting of vasomotor symptoms (17).
4 years and 10.2 years have been reported, along with Several studies have reported that hot flushes are
the observation that vasomotor symptoms commence more common in obese women (16, 18). Although the
around entry into the menopausal transition for some mechanism of this association is not understood, it has
women and are not limited to the years immediately been hypothesized that adipose tissue functions as an
around the final menstrual period (5, 11). This find- insulator and interferes with normal thermoregulatory
ing may be one explanation for the wide variation in mechanisms of heat dissipation. Adipose tissue also may
reported symptom duration. have an endocrine function that mediates vasomotor
The pathophysiology of the hot flush is not fully symptoms. Other factors related to vasomotor symptoms
understood and is likely related to multiple factors. include mood symptoms such as depression and anxiety,
Changes in reproductive hormones appear to play a low socioeconomic status, and smoking (4, 19).
critical role, given that these symptoms occur during the There are emerging data to suggest that vasomotor
menopausal transition and improve with the administra- symptoms may be associated with adverse health out-
tion of estrogen. Although observational studies suggest comes including, cardiovascular health and bone health
that decreased estrogen levels and elevated follicle-stim- (20, 21). However, recent data from The Kronos Early
ulating hormone levels are associated with vasomotor Estrogen Prevention Study noted that self-reported meno-
symptoms, these changes cannot be solely responsible pausal symptoms in recently menopausal women are not
for these symptoms because the occurrence and sever- strong predictors of subclinical atherosclerosis (22).
ity of symptoms varies greatly among women during
the menopausal transition (12). There also is evidence Vaginal Symptoms
that thermoregulatory mechanisms change during the Vaginal atrophy is a direct consequence of the hypoes-
transition so that the thermoregulatory zone is narrowed trogenic state associated with menopause resulting in
and becomes more sensitive to subtle changes in core anatomic and physiologic changes in the genitourinary
body temperature. Small increases in temperature trigger tract. The North American Menopause Society estimates
thermoregulatory mechanisms causing the sensation of that 10–40% of menopausal women will experience one
a hot flush (vasodilation, sweating, and decreased skin or more symptoms of vaginal atrophy. Vaginal atrophy
resistance). Physiologic studies exploring hot flushes have causes bothersome vaginal symptoms commonly associ-
confirmed that fluctuations in core body temperature are ated with menopause including, vaginal or vulvar dry-
more pronounced in postmenopausal women compared ness, discharge, itching, and dyspareunia (23). A loss
with premenopausal women and that administration of of superficial epithelial cells in the genitourinary tract
estrogen widens the regulatory zone (9). Other central causes thinning of tissue. Loss of vaginal rugae and
physiologic mechanisms that play a role in vasomotor elasticity occur with a narrowing and shortening of the
symptoms include the serotonergic, noradrenergic, opioid, vagina. Epithelial tissues are more fragile and may tear,
adrenal, and autonomic systems (9). Evidence for a genetic leading to bleeding and fissures. There also is a loss of
predisposition to vasomotor symptoms stems from stud- subcutaneous fat in the labia majora. These changes
ies that have found a link between symptoms and several result in narrowing of the introitus, fusion of the labia
polymorphisms related to sex steroid metabolism (13). minora, and shrinking of the clitoral prepuce and urethra.
Epidemiologic studies have been performed to iden- Vaginal pH becomes more alkaline, which may alter the
tify risk factors for vasomotor symptoms. Racial and ethnic vaginal flora and increase the risk of urogenital infec-
differences have been shown to be important in vasomo- tion (24, 25). Vaginal secretions, largely transudate from
tor symptom reporting in several observational studies. the vaginal vasculature, may decrease. These changes
The Study of Women’s Health Across the Nation assessed from vaginal atrophy can lead to significant dyspareu-
menopausal symptoms in 14,906 women with diverse eth- nia, which can impair sexual function (26). Measures
nic backgrounds aged 40–55 years in the United States and of sexual dysfunction are noted to be present at higher
demonstrated that African American women reported the rates in women with vaginal atrophy than in unaffected
most vasomotor symptoms and Asian women reported menopausal women (27). Collectively these symptoms
the fewest symptoms compared with other groups (3, 14). may have a detrimental effect on a woman’s quality
Such racial and cross-cultural variability in the prevalence of life, self-esteem, and sexual intimacy (treatment of
of self-reported hot flushes is substantiated by other lit- sexual dysfunction is also discussed in Practice Bulletin
erature (15, 16). It is possible that physiologic differences Number 119, Female Sexual Function) (28). Genital
or diets high in soy products may account for variable examination and microscopic examination of vaginal
symptomatology. However, it also may be that ethnic smears can confirm atrophic vaginitis.

2 Practice Bulletin No. 141

Clinical Considerations and testosterone, or compounded bioidentical hormones for
the treatment of vasomotor symptoms (see Table 1).
Recommendations
Estrogen Alone or Combined With
What hormonal medications are effective in Progestin
treating vasomotor symptoms?
The results of multiple studies support the effectiveness
Systemic hormone therapy (HT), with estrogen alone or of HT for the management of menopausal vasomotor
in combination with progestin, is the most effective ther- symptoms. A Cochrane meta-analysis of 24 random-
apy for vasomotor symptoms related to menopause. Data ized controlled trials (RCTs), which included 3,329
do not support the use of progestin-only medications, participants found a 75% reduction in weekly hot flush

Table 1. Treatment Options for Menopausal Vasomotor Symptoms ^

Treatment Dosage/Regimen Evidence of Benefit* FDA Approved

Hormonal

Estrogen-alone or combined
with progestin
• Standard Dose Conjugated estrogen 0.625 mg/d Yes Yes
Micronized estradiol-17b 1 mg/d Yes Yes
Transdermal estradiol-17b 0.0375–0.05 mg/d Yes Yes
• Low Dose Conjugated estrogen 0.3–0.45 mg/d Yes Yes
Micronized estradiol-17b 0.5 mg/d Yes Yes
Transdermal estradiol-17b 0.025 mg/d Yes Yes
• Ultra-Low Dose Micronized estradiol-17b 0.25 mg/d Mixed No
Transdermal estradiol-17b 0.014 mg/d Mixed No
Estrogen combined with Conjugated estrogen 0.45 mg/d and bazedoxifene Yes Yes
estrogen agonist/antagonist 20 mg/d
Progestin Depot medroxyprogesterone acetate Yes No
Testosterone No No
Tibolone 2.5 mg/d Yes No
Compounded bioidentical
hormones No No

Nonhormonal

SSRIs and SSNRIs No No

Paroxetine 7.5 mg/d Yes Yes
Clonidine 0.1 mg/d Yes No
Gabapentin 600–900 mg/d Yes No
Phytoestrogens No No
Herbal Remedies No No
Vitamins No No
Exercise No No
Acupuncture No No
Reflexology No No
Stellate-ganglion block Yes No
Abbreviations: FDA, U.S. Food and Drug Administration; SSRIs, selective serotonin reuptake inhibitors; SSNRIs, selective serotonin norepinephrine reuptake inhibitors.
*Compared with placebo.

Practice Bulletin No. 141 3

frequency in users of oral estrogen or oral estrogen plus receive various doses of estradiol or placebo found that
progestin compared with placebo (95% confidence inter- a dosage as low as 0.5 mg/d of oral estradiol is effective
val [CI], 64.3–82.3) and a reduction in symptom severity in treating hot flushes (39).
(odds ratio [OR], 0.13; 95% CI, 0.07–0.23) (29). One of The results of studies that assessed the efficacy of
the largest studies investigating the effect of oral HT on ultra-low doses of estrogen (0.25 mg of oral micronized
vasomotor symptoms was the Postmenopausal Estrogen/ estradiol and 0.014 mg of transdermal estradiol) to treat
Progestin Interventions trial, an RCT of 875 women vasomotor symptoms have been mixed, and currently
treated with oral conjugated equine estrogen alone or these doses are not FDA approved for this indication.
in combination with continuous or cyclic progestin Some studies have shown improvement in vasomo-
versus placebo, which found a significant reduction in tor symptoms with ultra-low dose estrogen alone or in
self-reported vasomotor symptoms in women in both combination with progestin (36, 40, 41). For example, an
the estrogen-alone arm (OR, 0.42; 95% CI, 0.28–0.62) RCT of 425 women demonstrated that 41% of women
and the estrogen-plus-progestin arm (OR, 0.38; 95% CI, experienced a reduction in moderate and severe hot
0.25–0.58) compared with placebo (30). flushes with ultra-low dose estradiol therapy (0.014 mg/d
estradiol patch) compared with placebo (36). However,
Routes of Administration other studies have not shown a benefit for the treatment
There are a variety of preparations available for systemic of vasomotor symptoms (42). In an RCT of 333 women,
estrogen therapy. Estrogen with or without progestin can a 0.25-mg dose of oral estradiol was not more effective
be administered orally or transdermally in the forms of than placebo in treating hot flushes (39).
patches, gels, or sprays (31, 32). All of these delivery The degree of improvement of vasomotor symptoms
methods have been shown to relieve vasomotor symp- from low-dose and ultra-low dose preparations has not
toms, and also include other delivery methods, such as been as extensively studied as with standard-dose prepa-
intranasal and buccal systems that are not available in rations. Although women will experience improvement
the United States (33–35). in symptoms with low and ultra-low doses of HT, lower
doses do not appear to be as effective as traditional doses
Dose of HT in alleviating vasomotor symptoms. Nonetheless,
Studies of the efficacy of HT for the treatment of vaso- given the variable response to HT and the associated
motor symptoms have principally investigated standard risks, it is recommended that health care providers indi-
doses of HT. Although HT is well tolerated by most vidualize care and treat women with the lowest effective
women, standard doses may cause adverse effects, such dose for the shortest duration that is needed to relieve
as breast tenderness, vaginal bleeding, bloating, and vasomotor symptoms.
headaches. Low-dose and ultra-low systemic doses of
estrogen may be associated with a better adverse effect Risks
profile than standard doses and may reduce vasomotor The risks of systemic combined HT include thrombo-
symptoms in some women. embolic disease and breast cancer. The majority of trials
Examples of low-dose systemic estrogen therapy that analyzed the safety of HT have assessed prepara-
formulations include 0.3–0.45 mg/d of oral conjugated tions containing conjugated equine estrogen alone or
equine estrogen, 0.5 mg/d of oral micronized estradiol, in combination with medroxyprogesterone acetate. The
5 micrograms/d of ethinyl estradiol, and 0.025–0.0375 Women’s Health Initiative (WHI) study, a large RCT of
mg/wk of transdermal estradiol (patch). There also are healthy menopausal women aged 50–77 years, demon-
low-dose formulations of estradiol available in topical strated a slightly increased risk of breast cancer, coro-
gels, creams, and sprays that are approved by the U.S. nary heart disease, stroke, and venous thromboembolic
Food and Drug Administration (FDA). There is good events and a decreased risk of fractures and colon cancer
evidence that oral and transdermal low-dose estrogen after an average of 5 years of combined HT (43). Among
regimens effectively alleviate vasomotor symptoms women receiving estrogen only, there was an increased
in women (36–38). The Heart Outcomes Prevention risk of thromboembolic events, but not an increased risk
Evaluation, a large trial that assessed the efficacy of dif- of cardiovascular events or breast cancer (44). It is diffi-
ferent doses of HT on vasomotor symptoms in more than cult to generalize these findings to younger women who
2,500 postmenopausal women, found a similar reduction are recently menopausal because the WHI was aimed at
in vasomotor symptoms with a conjugated equine estro- assessing HT for primary coronary heart disease preven-
gen dosage of 0.625 mg/d and all lower combination tion in women, many of whom were past the menopausal
doses (38). Another study of 333 women randomized to transition.

4 Practice Bulletin No. 141

 A reanalysis of the WHI results in women younger and endometrial cancer in women with a uterus, there
than 60 years and within 10 years of menopause has is some evidence that progestin may also improve
suggested a possible cardioprotective effect of HT for vasomotor symptoms (56). Some studies suggest that
women in this group (45). However, a follow-up study improvement in vasomotor symptoms is greater com-
of the WHI with 13 years of cumulative follow-up data pared with placebo when progestin is added to estrogen
confirmed that the risk of conjugated equine estrogen (OR, 0.10; 95% CI, 0.06–0.19) compared with estrogen
and medroxprogesterone acetate outweighed the ben- alone (OR, 0.35; 95% CI, 0.22–0.56) (29). Moreover,
efits (46). Similarly, a 2012 Cochrane review of HT that there is some evidence that progestin-only therapy
included 23 studies and more than 42,000 participants is effective in reducing vasomotor symptoms. In an
concluded that HT should not be used for primary or RCT of 109 women treated with a single dose of depot
secondary disease prevention because the risks of use medroxyprogesterone acetate (400 mg) or venlafaxine
outweigh the benefits (47). 37.5 mg/d for 1 week and then 75 mg/d, those in the
The use of alternative forms of estrogen and pro- depot medroxyprogesterone acetate arm had a greater
gestin may be associated with a different risk profile reduction in vasomotor symptoms (79% versus 55%)
(48). For example, observational studies suggest that and less toxicity than those in the venlafaxine arm (57).
transdermal estrogen may have a lower risk of venous Although progestin may improve vasomotor symptoms,
thromboembolism compared with oral regimens (49). there are limited data on the safety of progestin alone
Additional data from RCTs are needed to compare the compared with combined estrogen and progestin prepa-
safety and efficacy of various regimens. rations for the treatment of vasomotor symptoms.
Because the risk of breast cancer was increased in
Discontinuation the conjugated equine estrogen and medroxproges-
Discontinuation of HT may be associated with recurrent terone acetate arm of WHI and not in the conju-
vasomotor symptoms in approximately 50% of women, gated equine estrogen-alone arm, there is concern that
regardless of age and duration of use (50–52). There is the risk of breast cancer may be related to progestin use.
insufficient evidence to recommend one method of HT Therefore, progestin alone is not considered a first-line
discontinuation (abrupt or tapering) over the other to therapy for the management of vasomotor symptoms.
prevent recurrent symptoms (53, 54). The decision to
continue HT should be individualized and be based on Testosterone
a woman’s symptoms and the risk–benefit ratio, regard- Testosterone in combination with HT has been inves-
less of age. Because some women aged 65 years and tigated for the treatment of menopausal symptoms. A
older may continue to need systemic HT for the man- Cochrane meta-analysis reviewed 35 trials with 4,768
agement of vasomotor symptoms, the American College postmenopausal women to determine the efficacy of
of Obstetricians and Gynecologists recommends against testosterone therapy in this population (58). Testosterone
routine discontinuation of systemic estrogen at age 65 for the treatment of vasomotor symptoms has shown
years. As with younger women, use of HT and estrogen no benefit and potential adverse effects including,
therapy should be individualized based on each woman’s detrimental effects on lipid parameters, clitoromegaly,
risk–benefit ratio and clinical presentation. hirsutism, and acne (58–60). However, in the Cochrane
As an alternative to the use of a progestin for meta-analysis, the pooled estimate suggested that the
preventing endometrial hyperplasia with estrogen ther- addition of testosterone to HT regimens improved sexual
apy, preparations combining estrogen and an estrogen function scores and number of satisfying sexual episodes
agonist/antagonist have been investigated. Recently, a for postmenopausal women (58). Testosterone alone is
combined daily oral preparation of conjugated estro- currently not FDA-approved for use in women.
gen and bazedoxifene has been approved by the FDA
for treatment of vasomotor symptoms and to prevent Tibolone
osteoporosis in postmenopausal women with a uterus. Tibolone is a synthetic steroid with tissue-specific estro-
This preparation has been shown to significantly reduce genic and progestogenic effects that has been studied
the number of vasomotor symptoms and significantly for the management of menopause. Tibolone is not
increase bone mineral density compared to placebo (55). FDA-approved and is not available in the United States.
Tibolone appears to have a beneficial effect on bone
Progestin density, vasomotor symptoms, and vaginal symptoms
Although progestin is primarily used as an add-on agent without estrogenic effects on the uterus or breasts (61,
to estrogen therapy to prevent endometrial hyperplasia 62). However, given its limited safety and efficacy data

Practice Bulletin No. 141 5

compared with HT, tibolone is not considered a first-line somnolence, sweating, and sexual dysfunction, but these
therapy for menopausal symptoms. generally resolved with time or dose adjustment.
Although the available evidence indicates that SSRIs
Compounded Bioidentical Hormones and SSNRIs appeared to be less effective than HT for the
Bioidentical hormones are plant-derived hormones that treatment of vasomotor symptoms, it is difficult to draw
are chemically similar or structurally identical to those definitive conclusions because direct comparisons with
produced by the body. Bioidentical hormones include estrogen are limited. Paroxetine (7.5 mg/d) is the only
commercially available products approved by the FDA, nonhormonal therapy that is approved by the FDA for
such as micronized progesterone and estradiol, as well the treatment of vasomotor symptoms.
as compounded preparations that are not regulated by
the FDA. Because of a lack of FDA oversight, most Clonidine
compounded preparations have not undergone any rig- Clonidine, a centrally acting alpha 2-agonist, is an anti-
orous clinical testing for either safety or efficacy, so the hypertensive agent that has been used to treat vasomotor
purity, potency, and quality of compounded preparations symptoms, but is not FDA-approved for this indication.
are a concern. In addition, both underdosage and over- Safety and efficacy data on this preparation for the
dosage are possible because of variable bioavailability management of vasomotor symptoms are limited. A
and bioactivity. Evidence is lacking to support superior- systematic review and meta-analysis reported a small
ity claims of compounded bioidentical hormones over benefit of clonidine (0.1 mg/d) compared with pla-
conventional menopausal HT (this is also discussed
cebo, but less benefit compared with HT (72). Common
in Committee Opinion Number 532, Compounded
adverse effects reported were dry mouth, insomnia, and
Bioidentical Menopausal Therapy). Conventional HT is
drowsiness. Blood pressure was not adversely affected
preferred given the available data (63).
by clonidine.
What nonhormonal medications are effective
for the treatment of vasomotor symptoms? Gabapentin
Gabapentin, a gamma aminobutyric acid analogue, is
Selective serotonin reuptake inhibitors (SSRIs), selective an anticonvulsant agent that has been shown to reduce
serotonin-norepinephrine reuptake inhibitors (SSNRIs), vasomotor symptoms in several studies but is not FDA-
clonidine, and gabapentin are effective alternatives to approved for this indication. An RCT of gabapentin
HT for the treatment of vasomotor symptoms related to (900 mg/d) demonstrated a 45% reduction in hot flush
menopause (see Table 1). frequency and a 54% reduction in symptom sever-
ity (73). Another trial of 45 women with moderate-to-
Selective Serotonin Reuptake Inhibitors severe hot flushes randomized to receive gabapentin
and Selective Serotonin-Norepinephrine (600 mg/d) versus a low-dose transdermal estradiol (25
Reuptake Inhibitors micrograms/d) showed symptom relief in both groups,
but estrogen was more effective (74). Common adverse
There is increasing evidence that the antidepressant effects from gabapentin include dizziness, somnolence,
agents SSRIs and SSNRIs are effective for the treatment and peripheral edema. Gabapentin, SSRIs, and SSNRIs
of vasomotor symptoms associated with menopause. appear to have similar treatment efficacy for vasomotor
Although data are mixed, the results from RCTs support symptoms, but the majority of women who were admin-
the effectiveness of these medications for the treatment istered both venlafaxine and gabapentin in a crossover
of menopausal hot flushes in healthy, nondepressed trial preferred venlafaxine (75).
women (64–71). In an RCT of 365 women, 62% of those
treated with the SSNRI, desvenlafaxine (100 mg/d), had What complementary and alternative
a reduction of 5.35 moderate-to-severe hot flashes per therapies are effective for the treatment of
day compared with only 41% of women with placebo,
vasomotor symptoms?
and the treatment effect was maintained for 1 year (69,
70). The results of a meta-analysis of earlier studies of
SSRIs or SSNRIs for the management of vasomotor Complementary Botanicals and
symptoms demonstrated a significant reduction com- Natural Products
pared with placebo (mean difference, −1.13; 95% CI, Several natural products have been used for the man-
−1.70 to −0.57) (72). Reported adverse effects included agement of vasomotor symptoms. In the United States,
nausea, dizziness, dry mouth, nervousness, constipation, none of these complementary therapies are regulated by

6 Practice Bulletin No. 141

the FDA and have not been tested for safety, efficacy, Black cohosh (also known as Actaea racemosa or
or purity because they are considered nutritional supple- Cimicifuga racemosa) is a plant that is widely used to
ments. Data do not show that phytoestrogens, herbal treat vasomotor symptoms, although data are conflict-
supplements, and lifestyle modifications are efficacious ing regarding its efficacy and safety, due in part to lim-
for the treatment of vasomotor symptoms. ited study quality. In particular, liver toxicity has been
reported (80–83). There is currently insufficient evi-
Phytoestrogens dence to support the use of black cohosh for menopausal
Phytoestrogens are plant-derived substances with estro- symptoms, although further study is warranted (84).
genic biologic activity. Examples include the isoflavones Studies have not shown that other herbs including,
genistein and daidzein, which are found in high amounts ginseng, St. John’s wort, and ginkgo biloba, either alone
in soybeans, soy products, and red clover. Initial interest or in combination, are superior to placebo for the treat-
in using phytoestrogens for the treatment of menopausal ment of vasomotor symptoms (85–88).
symptoms stemmed from the observation that Asian
women, whose diets are rich in phytoestrogens from Vitamins
soy, experience fewer vasomotor symptoms and have a There are limited data on the effectiveness of vitamin
lower risk of estrogen-sensitive cancer compared with supplements for the treatment of vasomotor symptoms
Caucasian women. Although multiple studies have been (89, 90). One less hot flush per day, a marginal reduc-
conducted to assess the efficacy of these substances on tion, has been reported with the use of vitamin E (800
the management of menopause related vasomotor symp- international units/d) (89).
toms, most of the data are limited by small sample size,
assessment of various forms of phytoestrogen products,
Alternative Techniques
and variability in dose and duration of trials. A 2010
Cochrane meta-analysis of 30 placebo-controlled trials Several studies have been conducted to assess the effec-
of high levels of phytoestrogens for the treatment of tiveness of acupuncture for the management of vasomo-
vasomotor symptoms found no evidence of benefit (76). tor symptoms. A meta-analysis of six RCTs showed
In particular, there was no significant difference in the no benefit over placebo for vasomotor symptoms (91).
frequency of hot flushes between red clover extract and Similarly, reflexology has not been shown to signifi-
placebo (weighted mean difference, −0.6; 95% CI, −1.8 cantly reduce vasomotor symptoms compared with non-
to 0.6). There was no evidence of detrimental effects, specific foot massage (92). There are some preliminary
such as overstimulation of the endometrium, with use data to suggest that local injection of anesthetic into the
up to 2 years. Nonetheless, long-term safety data are stellate ganglion may reduce vasomotor symptoms in
lacking. women with contraindications to HT (93, 94). However,
additional studies are needed to assess the safety and
Herbal Remedies effectiveness of this novel technique.
Herbal treatments that have been studied for the relief
of vasomotor symptoms include Chinese herbal medi- What behavioral and lifestyle changes are
cine, black cohosh, ginseng, St. John’s wort, and ginkgo effective in treating vasomotor symptoms?
biloba. There are currently insufficient data to support
the use of herbal remedies for menopausal–vasomotor Despite limited supporting data, common sense lifestyle
symptoms. solutions such as layering of clothing, maintaining a
Chinese herbal medicine treatments, often contain- lower ambient temperature, and consuming cool drinks
ing the plant dong quai (Angelica sinensis), have been are reasonable measures for the management of vaso-
used to treat vasomotor symptoms, with limited data to motor symptoms. Women also may be advised to avoid
support safety and effectiveness. In one RCT, dong quai consumption of alcohol and caffeine, which have been
was not found to be more effective than placebo, and associated with increased severity and frequency of
potential adverse effects included photosensitivity and vasomotor symptoms (95).
an increased risk of bleeding in patients using warfarin Although there is some evidence that aerobic exer-
(77). Another Chinese herb, dang gui bu xue tang, has cise may improve quality of life and mood in women
been found to be more effective than placebo for the with vasomotor symptoms, there are insufficient data
management of mild vasomotor symptoms (78). In one to recommend exercise for the treatment of vasomotor
study, Chinese herbal medicine plus acupuncture was symptoms (96). A meta-analysis of six small RCTs that
found to be as effective as HT at relieving menopausal evaluated exercise interventions for vasomotor symp-
symptoms (79). toms revealed no significant improvement compared

Practice Bulletin No. 141 7

with placebo (standard mean difference, −0.14; 95% CI, diol are clinically significant, and whether the effects of
−0.54 to 0.26) (97). A systematic review of studies that long-term exposure pose increased risk, nonhormonal
compared exercise interventions with HT showed a methods should be considered first-line treatment for
greater benefit for HT, but the difference was not statisti- vaginal atrophy in women with a history of hormone-
cally significant (standard mean difference, 0.49; 95% CI, sensitive breast cancer (106). Short-term use of hormonal
−0.27 to 1.26) (98). methods may be considered for women with severe or
refractory symptoms in whom other options have failed,
What hormonal medications are effective in following appropriate counseling with their oncologists
treating vaginal symptoms? about the potential risks (105).

Estrogen Estrogen Agonists and Estrogen

Estrogen therapy effectively alleviates atrophic vagi- Antagonists
nal symptoms related to menopause. Local therapy is Estrogen agonists and estrogen antagonists are synthetic
advised for the treatment of women with only vaginal compounds that selectively stimulate or inhibit the estro-
symptoms. All low-dose systemic estrogen formula- gen receptors of different target tissues. Such selectiv-
tions are FDA-approved for the treatment of atrophic ity is possible because estrogen receptors in different
vaginitis. Oral dosages of conjugated equine estrogen target tissues vary in chemical structure (105). The
as low as 0.3 mg/d and transdermal estradiol dosages of physiologic effects of estrogen agonists and estrogen
12.5 micrograms/d have demonstrated improvements in antagonists are not uniform and vary depending on the
vaginal atrophy (38, 98). type of estrogen agonist or estrogen antagonist. Because
Local vaginal estradiol and local conjugated equine estrogen agonists and estrogen antagonists selectively
estrogen, which can be administered in cream, ring, and stimulate or inhibit the estrogen receptors of different
tablet formulations, are effective in treating atrophic target tissues, their effects in some tissues can have a
vaginitis in menopausal women (99–101). The results deleterious physiologic effect, including an increased
of RCTs show that even low-dose (10 micrograms) risk of thromboembolic events, endometrial and vulvo-
vaginal estradiol tablets improve vaginal symptoms vaginal abnormalities, and vasomotor problems. Studies
(102, 103). Typically, vaginal estrogen formulations are demonstrate that two currently available FDA-approved
administered daily for 1–2 weeks as induction therapy agents, raloxifene and tamoxifen, are not effective for
and then may be used indefinitely at low doses for the treatment of menopausal vaginal symptoms (107).
maintenance therapy. Studies indicate that the 3-month The current evidence does not suggest an important
estradiol-releasing vaginal ring is preferred to cream effect of either agent for the treatment of vasomotor
because of greater comfort, ease of use, and satisfac- symptoms. However, studies suggest that ospemifene, a
tion (101). novel estrogen agonist and estrogen antagonist improves
Systemic absorption of vaginal estrogen has been vaginal atrophy without stimulating the endometrium.
documented in postmenopausal women with atrophy A study of 826 postmenopausal women randomized to
using a daily low-dose vaginal estrogen preparation with receive 30 mg/d or 60 mg/d of ospemifene showed that
25 micrograms of estradiol (104). There is a theoretic the 60-mg dose was effective for improving vulvovagi-
concern that systemic absorption may increase the risk of nal atrophy (108). Common adverse effects of ospemi-
endometrial cancer. However, a Cochrane meta-analysis fene reported during clinical trials included hot flushes,
of 19 trials with 4,162 women found that local estrogen vaginal discharge, muscle spasms, genital discharge, and
therapy was not associated with an increased risk of endo- excessive sweating. The FDA approved ospemifene for
metrial hyperplasia compared with placebo and, therefore, treating moderate-to-severe dyspareunia in postmeno-
the addition of progestion for endometrial protection is not pausal women (see Table 2).
needed (102). Use of progestin or local estrogen therapy
does not require endometrial surveillance, unless women What nonhormonal therapies are effective in
experience postmenopausal bleeding, which would require treating vaginal symptoms?
diagnostic evaluation.
Because of variable rates of estrogen absorption
associated with local estrogen therapy, there has been Vaginal Lubricants
concern about the use of this treatment in women with Nonestrogen water-based or silicone-based vaginal lubri-
a history of breast cancer (105). Because of the lack of cants and moisturizers may alleviate vaginal symptoms
data to determine whether transient increases in estra- related to menopause. These products may be particularly

8 Practice Bulletin No. 141

Table 2. Treatment Options for Menopausal Vaginal Symptoms ^

Treatment Dosage Evidence of Benefit* FDA Approved

Hormonal

Estrogen
Systemic
• Standard Dose Conjugated estrogen 0.625 mg/d Yes Yes
Micronized estradiol-17b 1 mg/d Yes Yes
Transdermal estradiol-17b 0.0375–0.05 mg/d Yes Yes
• Low Dose Conjugated estrogen 0.3–0.45 mg/d Yes Yes
Micronized estradiol-17b 0.5 mg/d Yes Yes
Transdermal estradiol-17b 0.025 mg/d Yes Yes
• Ultra-Low Dose Micronized estradiol-17b 0.25 mg/d Mixed No
Transdermal estradiol-17b 0.014 mg/d Mixed No
Vaginal/Local Estradiol-17b ring 7.5 micrograms/d Yes Yes
Estradiol vaginal tablet 25 micrograms/d Yes Yes
Estradiol ring 0.05 mg/d Yes
Estradiol-17b cream 2 g/d Yes
Conjugated estrogen cream 0.5–2 g/d Yes

Nonhormonal

Estrogen agonists–antagonists
• Raloxifene and tamoxifen No No
• Ospemifene 60 mg/d Yes Yes
Vaginal lubricants Yes No
Vaginal moisturizers Yes No
Herbal remedies and soy products No No
Abbreviation: FDA, U.S. Food and Drug Administration.
*Compared with placebo.

helpful in women who do not wish to use hormonal thera-

pies. Vaginal lubricants are intended to be used to relieve
Summary of
friction and dyspareunia related to vaginal dryness during Recommendations and
intercourse and are applied to the vaginal introitus before
intercourse. Vaginal moisturizers are intended to trap
Conclusions
moisture and provide long-term relief of vaginal dryness. The following recommendations and conclusions
Although there are limited data regarding the effective- are based on good or consistent scientific evidence
ness of these products, prospective studies have demon- (Level A):
strated that vaginal moisturizers improve vaginal dryness,
pH balance, and elasticity and reduce vaginal itching, Systemic HT, with estrogen alone or in combination
irritation, and dyspareunia (109), and many women have with progestin, is the most effective therapy for
found nonhormonal vaginal lubricants and moisturizers vasomotor symptoms related to menopause.
to be effective in managing vaginal dryness (see Table Low-dose and ultra-low systemic doses of estrogen
2) (110). There are insufficient data to support the use are associated with a better adverse effect profile
of herbal remedies or soy products for the treatment of than standard doses and may reduce vasomotor
vaginal symptoms (111, 112). symptoms in some women.

Practice Bulletin No. 141 9

 Given the variable response to HT and the associ-
ated risks, it is recommended that health care pro-
Proposed Performance
viders individualize care and treat women with the Measure
lowest effective dose for the shortest duration that is Documentation of the discussion with patients about the
needed to relieve vasomotor symptoms. severity of vasomotor and vaginal menopausal symp-
The risks of combined systemic HT include throm- toms and therapeutic options
boembolic disease and breast cancer.

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 82. Newton KM, Reed SD, LaCroix AZ, Grothaus LC, 94. Lipov EG, Joshi JR, Sanders S, Wilcox K, Lipov S, Xie H,
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14 Practice Bulletin No. 141

106. Files JA, Ko MG, Pruthi S. Managing aromatase inhibi-
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duct a literature search to locate relevant articles pub-
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Menopause 2010;17:480–6. (Level I) [PubMed] ^ organizations or institutions such as the National Institutes
of Health and the American College of Obstetricians and
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cream in the symptomatic treatment of vaginal atrophy located by reviewing bibliographies of identified articles.
in postmenopausal women. Maturitas 1996;23:259–63. When reliable research was not available, expert opinions
(Level I) [PubMed] [Full Text] ^ from obstetrician–gynecologists were used.
110. Bachmann GA, Leiblum SR. The impact of hormones Studies were reviewed and evaluated for quality according
on menopausal sexuality: a literature review. Menopause to the method outlined by the U.S. Preventive Services
2004;11:120–30. (Level III) [PubMed] ^ Task Force:
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112. Reed SD, Newton KM, LaCroix AZ, Grothaus LC, case–control analytic studies, preferably from more
Grieco VS, Ehrlich K. Vaginal, endometrial, and than one center or research group.
reproductive hormone findings: randomized, placebo- II-3 Evidence obtained from multiple time series with or
controlled trial of black cohosh, multibotanical herbs, without the intervention. Dramatic results in uncon-
and dietary soy for vasomotor symptoms: the Herbal trolled experiments also could be regarded as this
type of evidence.
Alternatives for Menopause (HALT) Study. Menopause
III Opinions of respected authorities, based on clinical
2008;15:51–8. (Level I) [PubMed] ^
experience, descriptive studies, or reports of expert
committees.
Correction—January 2016 Based on the highest level of evidence found in the data,
recommendations are provided and graded according to the
In “Practice Bulletin No. 141: Management of Meno- following categories:
pausal Symptoms” from the American College of
Level A—Recommendations are based on good and con-
Obstetricians and Gynecologists (Obstet Gynecol
sistent scientific evidence.
2014;123:202–16), there is an error on page 3 in
Table 1. In the “Nonhormonal” section, for SSRIs and Level B—Recommendations are based on limited or incon-
SSNRIs, the “Evidence of Benefit” column reads “No” sistent scientific evidence.
but should read “Yes.” There also is an error on page Level C—Recommendations are based primarily on con-
9 in Table 2. In the “Hormonal” section under the sensus and expert opinion.
“Dosage” column, for “Vaginal/Local,” the dosage for
the estradiol vaginal tablet of “25/micrograms/d” is
incorrect and should be “10/micrograms/d.” Copyright January 2014 by the American College of Obstetri-
cians and Gynecologists. All rights reserved. No part of this
publication may be reproduced, stored in a retrieval system,
Correction—March 2018 posted on the Internet, or transmitted, in any form or by any
means, electronic, mechanical, photocopying, recording, or
In “Practice Bulletin No. 141: Management of otherwise, without prior written permission from the publisher.
Menopausal Symptoms” from the American College
of Obstetricians and Gynecologists, there is an error Requests for authorization to make photocopies should be
on page 8 in the first paragraph of the “Estrogen” directed to Copyright Clearance Center, 222 Rosewood Drive,
Danvers, MA 01923, (978) 750-8400.
section. In the last sentence, the transdermal estradiol
dosage incorrectly reads, “12.5 micrograms/d” and ISSN 1099-3630
should instead read, “0.014 mg/d.” The full, corrected The American College of Obstetricians and Gynecologists
sentence is as follows: “Oral dosages of conjugated 409 12th Street, SW, PO Box 96920, Washington, DC 20090-6920
equine estrogen as low as 0.3 mg/d and transdermal Management of menopausal symptoms. Practice Bulletin No. 141.
estradiol dosages of 0.014 mg/d have demonstrated American College of Obstetricians and Gynecologists. Obstet Gynecol
improvements in vaginal atrophy (38, 98).” 2014;123:202–16.

Practice Bulletin No. 141 15