The 2017 Hormone Therapy Position Statement of The North American Menopause Society

The North American Menopause Society 2017 Hormone Therapy Position Statement Advisory Panel

Disclosures

The North American Menopause Society (NAMS). 2018;24(7):728-753. 

In This Article

Menopause Symptoms: Benefits and Risks

Vasomotor Symptoms

Vasomotor symptoms are associated with diminished sleep quality, irritability, difficulty concentrating, reduced quality of life (QOL),[41] and poorer health status.[42] Vasomotor symptoms persisted on average 7.4 years in the Study of Women's Health Across the Nation[43] and appear to be linked to cardiovascular (CV), bone, and cognitive risks.[44–48] Compared with placebo, estrogen alone or combined with a progestogen was found to reduce weekly symptom frequency by 75% (95% CI, 64.3–82.3) and significantly reduce symptom severity (OR, 0.13; 95% CI, 0.07–0.23),[23] with no other pharmacologic or alternative therapy found to provide more relief.

Although the lowest-dose approved estradiol weekly patch (0.014mg/d) appears effective in treating VMS,[49] it is approved for prevention of osteoporosis but not vasomotor relief. Lower doses may have lower risks for VTE[50] and may reduce AEs such as breast tenderness or unscheduled vaginal bleeding.[51,52] Lower doses of HT (oral CEE 0.3 mg; oral 17β-estradiol ≤ 0.5 mg; or estradiol patch 0.025 mg may take 6 to 8 weeks to provide adequate symptom relief.

Progestogen formulations have been found to be effective in treating VMS,[53,54] studied with MPA 10 mg per day,[55] oral megestrol acetate 20 mg,[56] and MP 300 mg,[54] but no long-term studies have addressed the safety of progestogen-only treatment on menopause symptoms.

Vasomotor symptoms return in approximately 50% of women when HT is discontinued.[57,58] There is no consensus about whether stopping ''cold turkey'' or tapering is preferable.

Sleep Disturbances

A 2015 literature review found that HT in the form of low-dose estrogen or progestogen could improve chronic insomnia in menopausal women, with 14 of the 23 studies reviewed showing positive results, but data are conflicting about the link between VMS at menopause and objective polysomno-graphic measures of sleep. Oral progesterone has mildly sedating effects, reducing wakefulness without affecting day-time cognitive functions, possibly through a GABA-agonistic effect.

The Genitourinary Syndrome of Menopause (Vaginal Symptoms)

The genitourinary syndrome of menopause (GSM) includes the signs and symptoms associated with postmenopause-related estrogen deficiency involving changes to the labia, vagina, urethra, and bladder and includes VVA. Symptoms may include genital dryness, burning, and irritation; sexual symptoms of diminished lubrication and pain; and urinary symptoms of urgency, dysuria, and recurrent urinary tract infections (UTIs). Estrogen therapy is the most effective treatment for GSM.[32,63,64]

Low-dose vaginal estrogen preparations are effective and generally safe treatments for VVA[32,65] and include creams, tablets, and rings containing estradiol or CEE, available at doses that result in minimal systemic absorption.[64–66]

Because of the potential risk of small increases in circulating estrogens,[67] the decision to use low-dose vaginal ET in women with breast cancer should be made in conjunction with their oncologists.[68] This is particularly important for women on aromatase inhibitors (AIs) with suppressed plasma levels of estradiol, although no increased risk was seen in an observational trial of survivors of breast cancer on tamoxifen or AI therapy with low-dose vaginal ET during 3.5 years' mean follow-up.[70]

A progestogen is generally not indicated when ET is administered vaginally for GSM at the recommended low doses, although clinical trial data supporting endometrial safety beyond 1 year are lacking.

Nonestrogen therapies that improve vaginal VVA and are approved for relief of dyspareunia in postmenopausal women include ospemifene[71] and intravaginal DHEA.[72]

Urinary Tract Symptoms (Including Pelvic Floor Disorders)

Vaginal ET may improve incontinence by increasing the number of vessels around the periurethral and bladder neck region[73] and has been shown to reduce the frequency and amplitude of detrusor contractions to promote detrusor muscle relaxation.[74,75] Estrogen therapy, along with pelvic floor training, pessaries, or surgery, may improve synthesis of collagen and improve vaginal epithelium, but evidence for effectiveness for pelvic organ prolapse is lacking.[76]

Two large trials found that users of systemic HT (CEE 0.625 mg + MPA 2.5 mg) had an increased incidence of stress incontinence.[77,78] Increased incontinence was found in women using oral estrogen alone (RR, 1.32; 95% CI, 1.17–1.48) and in those using combined estrogen and progestogen (RR, 1.11; 95% CI, 1.04–1.18).[79] Vaginal estrogen use showed a decreased incidence of incontinence (RR, 0.74; 95% CI, 0.64–0.86) and overactive bladder, with one to two fewer voids in 24 hours and reduced frequency and urgency. A reduced risk of recurrent UTI with vaginal but not oral estrogen has been shown in RCTs.[80]

Sexual Function

Systemic HT and low-dose vaginal ET provide effective treatment of VVA, improving sexual problems by increasing lubrication, blood flow, and sensation in vaginal tissues.[81] Studies have not found any significant effect of ET on sexual interest, arousal, and orgasmic response independent from its role in treating menopause symptoms.[82–84]

If systemic HT is needed and women have low libido, transdermal ET formulations may be preferred to oral, given increased sex hormone-binding globulin and reduced bioavailability of testosterone with oral ET.[81,85,86]

Conjugated equine estrogen combined with bazedoxifene relieves dyspareunia and improves VVA and some aspects of sexual function in postmenopausal women.[87–90]

Key Points

Vasomotor symptoms.

  • Vasomotor symptoms may be caused by thermoregulatory dysfunction. They begin during perimenopause and may persist on average 7.4 years or longer, with ethnic differences. They affect QOL and appear to be linked to CV, bone, and brain health.

  • Hormone therapy remains the gold standard for relief of VMS.

  • Estrogen-alone therapy can be used for symptomatic women after hysterectomy.

  • For symptomatic women with a uterus requesting HT, combination therapy protects against endometrial neoplasia, either with a progestogen or as a combination of CEE and bazedoxifene.

  • For menopause symptom control, the lowest dose that offers relief should be used. Dosing and need for ongoing therapy for relief of menopause symptoms should be assessed periodically.

  • Micronized progesterone 300 mg nightly significantly decreases VMS (hot flashes and night sweats) compared with placebo and improves sleep. Synthetic progestins have also shown benefit in studies. No long-term study results are available.

Sleep disturbances.

  • During the menopause transition, women with VMS are more likely to report reduced sleep.

  • Hormone therapy improves sleep in women with bothersome nighttime VMS by reducing nighttime awakenings.

The genitourinary syndrome of menopause (vaginal symptoms).

  • Low-dose vaginal estrogen preparations are effective and generally safe for the treatment of VVA, with minimal systemic absorption, and preferred over systemic therapies when ET is considered only for GSM.

  • For women with breast cancer, low-dose vaginal estrogen should be considered and prescribed in consultation with their oncologists.

  • Progestogen therapy is not needed with low-dose vaginal ET, but randomized trial data are lacking beyond 1 year; postmenopausal bleeding in women using low-dose vaginal ET must be thoroughly evaluated.

  • Nonestrogen prescription therapies that improve VVA in postmenopausal women include ospemifene and intravaginal DHEA.

Urinary tract symptoms (including pelvic floor disorders).

  • Systemic HT does not improve urinary incontinence and may increase the incidence of stress urinary incontinence.

  • Low-dose vaginal ET may provide benefit for urinary symptoms, including prevention of recurrent UTI, overactive bladder, and urge incontinence.

  • Hormone therapy does not have FDA approval for any urinary health indication.

Sexual function.

  • Both systemic HT and low-dose vaginal estrogen increase lubrication, blood flow, and sensation of vaginal tissues.

  • Systemic HT generally does not improve sexual function, sexual interest, arousal, or orgasmic response in women without menopause symptoms.

  • If sexual function or libido are concerns in women with menopause symptoms, transdermal ET may be preferable over oral ET because of less effect on sex hormone-binding globulin and free testosterone levels.

  • Low-dose vaginal ET improves sexual function in postmenopausal women with GSM (symptomatic VVA).

  • Nonestrogen alternatives approved for dyspareunia include ospemifene and intravaginal DHEA.

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