What is the role of HRT in the treatment of menopausal symptoms?

Updated: Jun 06, 2018
  • Author: PonJola Coney, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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The main reasons for treating symptoms of the menopausal transition (MT) and actual menopause are as follows:

  • To provide relief of vasomotor symptoms

  • To reduce the risk of unwanted pregnancy

  • To avoid the irregularity of menstrual cycles

  • To preserve bone

  • To lower the risk of disease

  • To improve quality of life

Hormone replacement therapy should be individualized. [83] The time at which therapy should be begun depends on the patient’s presenting complaints (if any) and medical history. It is the opportune time to conduct a health evaluation, identify risk for osteoporosis and other specific diseases, and assess for alterable behavioral risk factors.

Whether a woman is in the MT or in actual menopause affects the choice of the most suitable type of therapy. Counseling regarding hormone therapy differs, depending on the patient’s age and hysterectomy status. Many factors, including personal history, family history, smoking, peer and commercial influences, culture, need for contraception, ethnicity, and economics, also play roles in the final decision, and all must be carefully weighed by the clinician and patient together.

Adverse effects of replacement therapy may include bloating, mastodynia, vaginal bleeding, and headaches. Selective estrogen receptor modulators (SERMs) and estrogen increase the risk of thromboembolic events. [5] Unexplained adverse effects are often the reason for discontinuance of therapy, and reassuring counseling as well as different options and dose combinations should be tried before therapy is stopped.

The use of hormone replacement therapy (HRT) also appears to be associated with an increased risk of acute pancreatitis. [84, 85] In a study of 31,494 women, researchers found that woman who never used HRT had an incidence of acute pancreatitis of 52 cases per 100,000 person-years, compared with an incidence of 71 cases per 100,000 person-years in woman who had used HRT. This translates to a 57% increased risk. [84, 85]

Controlling for waist circumference, the factors of alcohol consumption, age at menarche, parity, use of oral contraceptives, and history of diabetes did not significantly change these results. [84, 85] The increased risk did not differ by current or past HRT use, but the risk was higher in women who used systemic therapy.

Hormone therapy can be administered either systemically via the oral, transdermal, or topical routes or locally via the vaginal route in a cream, ring, or tablet. Topical preparations are used solely to treat vaginal symptoms.

Contraindications for estrogen therapy include undiagnosed vaginal bleeding, severe liver disease, pregnancy, venous thrombosis, and personal history of breast cancer. Well-differentiated and early endometrial cancer, once treatment for the malignancy is complete, is no longer an absolute contraindication. Progestins alone may relieve symptoms if the patient is unable to tolerate estrogens. 

It has been suggested that oral estrogens are associated with a higher risk of recurrent venous thromboembolism among postmenopausal women. [86] However, transdermal estrogens may be safe with respect to venous thromboembolism risk.

The combination product of bazedoxifene, a SERM, and conjugated estrogens (CEs) was approved by the FDA in October 2013. [87] Combining a SERM with CEs lowers the risk of uterine hyperplasia caused by estrogens. This eliminates the need for a progestin and its associated risks (eg, breast cancer, MI, VTE). This combination significantly reduced the number and severity of hot flashes at weeks 4 and 12 (P < 0.001). At week 12, bazedoxifene/CE reduced hot flashes from baseline by 74% (10.3 hot flashes [baseline] vs 2.8) compared with 51% (10.5 vs 5.4) for placebo. [88] Bazedoxifene/CE is FDA-approved for prevention of osteoporosis and treatment of vasomotor symptoms in postmenopausal women.

Alternative products (eg, herbal preparations and dietary supplements containing phytoestrogens), are reputed to ease the transition from perimenopause to postmenopause and are widely available. However, unlike pharmaceutical products, they have not been scrutinized in randomized, controlled trials. These over-the-counter products are assumed to act in the same manner as their pharmaceutical counterparts, but the herbal and vitamin industry is not regulated by the US Food and Drug Administration (FDA).

In a double-blind, randomized controlled trial, Lui et al observed a mild but significant favorable effect on body composition (eg, weight, body mass index [BMI], and fat percentage) in postmenopausal women who received 6 months of soy protein supplementation as compared with similar women who received milk protein. Each group also received isoflavones. [89]

However, in another randomized, double-blind trial that compared 200 mg of soy isoflavone supplementation with placebo, no difference was seen between the 2 groups with respect to bone mineral density (BMD) or menopausal symptoms. [90, 91]

In women who either cannot undergo estrogen or hormone therapy (because of a history of breast cancer) or choose not to do so and who suffer from hot flashes or flushes, the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs—in particular, venlafaxine) have been shown to alleviate vasomotor symptoms. A study by Freeman et al found that the use of the SSRI escitalopram in a dosage of 10-20 mg/day can help reduce and alleviate more severe hot flashes. [92]

Japanese traditional medicines such as keishibukuryogan and kamishoyosan have also shown to reduce the circulating interleukin (IL)-8 level in perimenopausal women and to decrease the circulating monocyte chemotactic protein (MCP)-1 level in postmenopausal women. [93]

A study by Freeman et al suggested that the median duration of hot flashes actually exceeds the timeframe generally accepted in clinical practice. [94] Clinicians should consider identifiable risk factors such as menopausal stage, race, and BMI when creating individualized treatment plans and evaluating the risk-to-benefit ratios of hormone replacement and other therapies.

Estrogens and progestins are prescribed for both prevention and therapy, and the expectations for the 2 uses are very different. Relief of vasomotor and vaginal symptoms is the primary indication for hormone therapy. Hormones are the most effective agents available for vasomotor-related symptoms and remain the standard of care. Efficacy can be achieved with lower doses than are traditionally used. Frequent nighttime sleep disruption due to hot flashes may be relieved by synthetic conjugated estrogens-B in dosages as low as 0.3 mg/day. [95]  In a review by Prior, oral micronized progesterone (OMP) appears to effectively treats vasomotor symptoms and sleep disturbances, and monotherapy is potentially safe for symptomatic menopause. [96]

The duration of use should be dictated by individual symptoms and related risks. The benefits of hormone therapy are clear for women who initiate therapy close to menopausal age, but such therapy is considered riskier with continuing use and advancing age. Additional and ongoing studies will help determine the risks and potential benefits of longer-term therapy.

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