"Custom-compounded hormones should be reserved for situations in which a patient is allergic to or does not tolerate any of the FDA-approved therapies and treatment is necessary for his or her health," lead author Nanette Santoro, MD, professor and chair of obstetrics and gynecology at the University of Colorado School of Medicine in Aurora, said during a press briefing here at ENDO 2016, the annual meeting of the Endocrine Society. The statement was published online April 1, 2016 in the Journal of Clinical Endocrinology and Metabolism.

The statement is the latest in a series from medical societies, including the American College of Obstetricians and Gynecologists and the North American Menopause Society, cautioning against the use of custom-compounded, so-called "bioidentical" hormones. Nonetheless, many physicians are still prescribing them.

Indeed, Dr Santoro cited survey data that up to a quarter or a third of all menopause therapy prescriptions are for custom-compounded products, garnering about $1 billion in annual sales. "This to us seems somewhat absurd when we have a large variety of what are technically the same bioidentical hormones that are FDA approved….It's kind of unfortunate that we live in an era where this has become so widespread it's a very big business."

Custom-compounded products are potentially dangerous, she said, because added excipients can affect absorption, and those or other added ingredients could be contaminated or adulterated. Moreover, she noted, FDA-approved hormone products have well-characterized pharmacokinetics and efficacy and safety profiles. In contrast, "There's no such thing in the world of custom-compounded bioidentical hormones."

Endocrinologist Mark Sklar, MD, told Medscape Medical News that he agrees with the Endocrine Society's new statement and stance. "I think that there's no real reason to compound, especially gonadal hormones like estrogen or testosterone, because there are very good commercially available hormones now. They're well-made and well-tested, and there's consistency. With compounding there's not consistency in dosage."

Dr Sklar, who is an assistant professor of medicine and endocrinology at Georgetown University Medical Center and George Washington University Medical Center, Washington, DC, added, "People who advocate compounding tell patients that the compounded medications don't have the same side effects. The article states, as I previously believed, that there are probably side effects; they're just not tested with the compounded agents like they are with the commercially available hormones. So I do agree with the statement and would not promote compounding in my practice."

"Numerous FDA-Approved Formulations"

Aimed at primary-care clinicians as well as endocrinologists, the Endocrine Society's new document provides detailed reviews of the biology and pharmacology of sex steroids and thyroid-hormone action, including available clinical-trial data for the FDA-approved products.

Among the key points:

• There are numerous FDA-approved formulations, both oral and nonoral, that have been recommended for menopausal hormone therapy, and therefore there is no rationale for use of nonapproved products. Nonoral estradiol may be associated with a reduced risk for venous thromboembolism and stroke.
• Micronized progesterone (MP), which has a superior metabolic profile and possibly lower risk of breast cancer, is preferred by some experts as first-line progestin therapy for women taking menopausal hormone therapy. Although biochemically it is apparently beneficial, evidence demonstrating a benefit of MP on clinical outcomes is lacking.
• There is no rationale for using compounded progesterone preparations of unknown pharmacokinetics, because there are many on-label pharmaceutical-grade preparations available and a real risk of harm associated with inadequate progesterone dosing.
• There are no randomized, double-blind, placebo-controlled trials demonstrating efficacy of compounded bioidentical hormone therapy in alleviating menopausal symptoms or other clinical conditions.
• Moreover, there are no comparative-effectiveness studies of equivalent doses of compounded bioidentical hormones compared with FDA-approved hormone treatments.
• Transdermal patches, gels, and intramuscular preparations of bioidentical testosterone are available and FDA approved for use in men with hypogonadism.
• There are currently no FDA-approved testosterone preparations for women.
• Custom-compounded testosterone for women can result in overdosing and cause harm.
• There are currently no FDA-approved preparations of dehydroepiandrosterone (DHEA), and there are no indications for its use except perhaps for some women with a low libido associated with adrenal insufficiency.
• Non–FDA-approved preparations of DHEA have all the caveats related to dosing, pharmacokinetics, and safety associated with estradiol, progesterone, and testosterone.
• The use of custom-compounded bioidentical DHEA is unlikely to be beneficial and is potentially harmful to patients.
• Vaginal DHEA is currently undergoing testing as an alternative to vaginal estrogen for the treatment of menopausal vaginal atrophy, but there is no vaginal DHEA preparation that is FDA approved for clinical use at this time.
• Levothyroxine (LT4) is bioidentical and a highly effective and safe therapy and is the treatment of choice for hypothyroidism. The complex tissue-specific deiodinase system converts T4 to T3 and supplies the proper amount of T3 to each of the body's tissues according to its requirements.
• Clinicians should evaluate patients with persistent symptoms (despite adequate LT4 therapy) for other causes of their symptoms and encourage patients to engage in healthy lifestyle measures.
• Some of these patients may benefit from combination LT4/LT3 therapy, desiccated thyroid hormone, or compounded thyroid hormone, as long as symptoms and thyroid-stimulating hormone (TSH) (free T4) are monitored carefully.

Asked whether there was any type of patient for whom he might use a compounded hormone formulation, Dr Sklar replied, "Not with estrogen or testosterone. I don't see any reason for that." He had previously tried it with thyroid hormone, "but the levels were very variable and not reliable at all.

"The only indication I might try compounding is women who need testosterone, since there is no good commercially available testosterone. Sometimes you have to resort to compounding to get that….Some women complain of low libido. Low-dose testosterone sometimes works for that. But I don't use it that often."

In a written statement, Dagmar Anderson, vice president of communications for the International Academy of Compounding Pharmacists (IACP), told Medscape Medical News, "IACP believes the patient has the choice to opt for a compounded medication, and that decision should be made with his/her physician."

Dr Santoro has received grant support from Bayer and stock options from Menogenix; disclosures for the coauthors are listed in the article. Dr Sklar has disclosed no relevant financial relationships.

J Clin Endocrinol Metab. Published online April 1, 2016. Abstract