A new verdict for hormone therapy (HT): Safe for younger, symptomatic women

ROUTE AND DOSAGE

HT preparations are available with various administration routes and dosages.¹² Therapy should be initiated at the lowest available dose. Symptoms should be reassessed after 8 to 12 weeks of therapy, and the dosage adjusted accordingly. Approximately 10% of patients may need to have their dosage increased.¹¹

The most common forms of HT are oral medications, transdermal patches, topical gels and creams, vaginal creams, tablets, or rings. To date, no RCTs indicate any advantages of one route over another. Oral preparations are subject to first-pass effect; however, because of the effects of higher estrogen levels on the liver when taken orally, the transdermal forms are preferred for women with hypertension, hypertriglyceridemia, or a high risk for cholelithiasis.1 In addition, some observational data indicate that the risk for deep vein thrombosis is lower with transdermal estrogen than with oral estrogen.³

Progestogen doses in EPT should be high enough to protect the endometrium but low enough to avoid the associated adverse events. Side effects range from headaches, nausea, abdominal pain, water retention, and weight gain to more serious events such as blood clots leading to MI, stroke, pulmonary embolism, or eye problems. Protective properties depend on the corresponding dose and frequency of estrogen and the progestogen preparation used.⁸ Progestogen can be administered continuously or cyclically. It is taken for 10 to 14 days every month when administered cyclically and produces a monthly menstrual cycle. Women who take progestogen continuously or daily experience amenorrhea, which typically results in better adherence.¹

Unopposed estrogen should be administered as a vaginal preparation. Local estrogen is highly effective and is preferred over systemic estrogen for women with only vaginal symptoms. Systemic absorption is limited with vaginal preparations; therefore, concomitant progestogen is not indicated.¹⁰ Local estrogen, however, has no effect on vasomotor symptoms or osteoporosis prevention, and this should be explained to patients.

DURATION OF THERAPY

The length of HT use is based on the reason for therapy. Ideally, the patient's symptoms and the dosage and form used should be reevaluated as part of her annual examination.¹¹ The need for further treatment is determined by discontinuing HT after 2 to 3 years. If symptoms recur, treatment can be resumed.

Some women may need long-term therapy. The NAMS guidelines recommend that as long as a woman is aware of her personal risks, she should be allowed to continue HT if she feels that the benefits outweigh her risks.3 This is especially true if her symptoms recur after an attempt to discontinue HT.³ A patient who opts for long-term therapy should be taking the lowest effective dosage. Patients may also choose to extend treatment when alternative therapies are not appropriate, cause unacceptable side effects, or the benefit-risk ratio of long-term use of an alternative therapy is unknown.³

DISCONTINUATION OF THERAPY

Most women are able to discontinue HT in less than 1 year.1 Researchers are divided, however, on how to discontinue HT. Many researchers recommend tapering the dose, but this has not been shown to result in any fewer side effects than stopping HT abruptly. Nonetheless, some clinicians recommend gradually decreasing the daily dosage, the number of days taken per week, or both.¹³ In one study, 25% of women were unable to discontinue HT because they developed withdrawal symptoms.¹⁴ Of the women who successfully stopped, 71% were stopped abruptly and 29% had their doses tapered.¹⁴

As when initiating HT, discontinuing therapy requires individualized attention. Some women will be able to discontinue HT more quickly—experiencing either no or fewer side effects—than other women. If the risks of continuing therapy are great but symptoms remain, an alternative treatment may be initiated to facilitate the transition. For instance, if hot flashes recur, a selective serotonin-receptor inhibitor (SSRI) or selective norepinephrine receptor inhibitor (SNRI) may be helpful.¹⁵

ALTERNATIVE TREATMENT OPTIONS

Women who cannot use HT may find relief with alternative therapies. Simple lifestyle modifications, such as dressing in layers, keeping the home temperature cooler, and practicing deep breathing and relaxation techniques may reduce or relieve hot flashes. Alternative pharmacologic therapies are also available. Low-dose antidepressants, such as venlafaxine 75 mg, an SNRI, were shown to effectively decrease hot flashes.¹⁶ Many SSRIs, such as paroxetine, can effectively treat vasomotor symptoms.¹⁷ A meta-analysis of RCTs supports using these agents as well as gabapentin and clonidine; however, the latter two agents may carry more side effects.¹⁵ Bisphosphonates, such as alendronate, risedronate, and ibandronate, are indicated to prevent and treat osteoporosis. SERMs have the same beneficial effects of estrogen (ie, increasing bone density) but without some of the adverse effects of estrogen in other tissues.¹⁵

The most popular OTC remedies are soy products, black cohosh, and vitamin E. Soy products contain isoflavones, a type of phytoestrogen. When metabolized, isoflavones are similar to human estrogen in structure and have a similar effect on estrogen receptors. Results of RCTs on the effectiveness of isoflavones in reducing hot flashes are inconclusive, and women with a history of hormone-dependent cancers, thromboembolic disease, or cardiovascular disease are cautioned about using soy because of its weak estrogenic effects.¹ The amount of isoflavones used in studies on treatment of menopausal symptoms was 40 to 80 mg daily for up to 6 months.¹ AACE recommends that women who wish to take isoflavones for their menopausal symptoms use whole food sources, not supplements.¹

Black cohosh has been used in Germany to treat hot flashes for many years. However, randomized, placebo-controlled trials have yielded inconsistent results regarding efficacy.¹ Black cohosh is thought to be relatively safe, but package labeling states it should not be used for more than 6 months. Vitamin E is also considered safe; however, it has not been proven to be any more effective than placebo.¹

The efficacy of bioidentical hormones has been debated. The chemical composition of bioidentical hormones is identical to the hormones produced by the human ovaries,³ namely 17 beta-estradiol and progesterone, and some preparations have FDA approval. However, the term bioidentical often refers to non-FDA-approved, custom compounded formulations that are available by prescription from special compounding pharmacies. Ingredients and routes of administration are different with custom compounded preparations compared with those used with standard, commercial hormone preparations. The dosage is usually determined via a saliva test, which is a controversial test that is not proven to be accurate or consistent. These compounded hormones have not been tested for safety or efficacy and are not approved or standardized by any regulatory agencies.³ Patients should assume that compounded hormones have similar or increased risks compared with standard preparations until more evidence is gathered.³

CONCLUSION

Clinicians should adapt their patients' treatment plans and expectations as more information becomes available. The key concepts are individualized care and thorough patient education. Defining an accurate profile of risks and benefits of HT for each patient and involving the patient in the decision-making process will keep expectations realistic and produce more desirable outcomes. Treatment of menopausal symptoms is a complex area of medicine, but HT has promising benefits for symptomatic women. JAAPA

Janie Knotts is a recent graduate of the PA program at Marietta College, Marietta, Ohio, and now works in family medicine in West Virginia. Bill Childers is a professor in the program and was Ms Knotts' advisor. They have indicated no relationships to disclose relating to the content of this article.

Alendronate (Fosamax, generics)
Clonidine (Catapres, generics)
Gabapentin (Gabarone, Neurontin, generics)
Ibandronate (Boniva)
Paroxetine (Paxil, Pexeva, generics)
Conjugated estrogen/medroxyprogesterone acetate (Prempro)
Risedronate (Actonel)
Venlafaxine (Effexor, generics)

REFERENCES

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