The Clinical Utility of Compounded Bioidentical Hormone Therapy A Review of Safety, Effectiveness, and Use (2020) / Chapter Skim
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6 Bioavailability of Compounded Bioidentical Hormone Therapy Preparations
6 Bioavailability of Compounded Bioidentical Hormone Therapy Preparations
Pages 117-136
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From page 117... ...
-- often the case with compounded preparations -- its bioavailability, and ultimately its safety and efficacy, would be unknown. In the absence of bioavailability data, there are important variables to consider, including, but not limited to, the particle size of the API, degree of mixing and type of mixing equipment used to make a given preparation, route of drug administration, and presence of other excipients (nonactive 1 Bioavailability refers to the amount of administered drug or substance within the body that is free to have an active effect on biological targets.
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From page 118... ...
Without reliable bioavailability data, an accurate characterization of the safety and effectiveness of cBHT preparations is not possible. MEASURING CONCENTRATIONS OF STEROID HORMONES Current clinical guidance suggests there is insufficient evidence to support claims that multiple blood, serum, or saliva tests can be used to precisely individualize hormone therapy (e.g., ACOG, 2018; Endocrine 4 This report does not specifically address the role of protein binding and its effect on bio availability of compounded preparations owing to lack of data.
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From page 119... ...
(CDC, 2008) 5 As an example, the North American Menopause Society states that hormone concentra tions are not required to determine whether a woman has the "right amount" of hormones, since the optimal hormone concentrations in postmenopausal women have not, in fact, been established (NAMS, 2020)
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From page 120... ...
. In one study, for example, researchers compared salivary versus serum testosterone concentrations in postmenopausal women receiving transdermal testosterone supplementation (Flyckt et al., 2009)
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From page 121... ...
(See the section "Bioanalytical Methods to Measure the Bioavailability of Steroid Hormones" in this chapter for an addiional t discussion on this topic.) Measuring Hormone Concentrations: Urine Testing Physicians who prescribe cBHT may also advocate for the use of urine testing to measure hormone levels.
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From page 122... ...
. Recently, investigators evaluated urinary estrogen and progesterone metabolites using dried filter paper samples and gas chromatography with tandem mass spectrometry (Newman et al., 2019)
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From page 123... ...
BIOAVAILABILITY OF COMPOUNDED BIOIDENTICAL HORMONE THERAPY PREPARATIONS From the limited bioavailability data on cBHT preparations that exist in the literature, the following four studies on compounded estrogen cream, testosterone pellets, progesterone cream, and a lozenge containing estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) serve as examples of how such studies are conducted.
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From page 124... ...
. The American Medical Association commented on this study, concluding that given the unpredictable pharmacokinetics of compounded formulations, the use of cBHT cannot be supported in comparison to well-tested FDA-approved hormone therapy options (AMA, 2016)
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From page 125... ...
Example Study 2: Compounded Testosterone Subcutaneous Pellet Study Design and Results Investigators (Glaser et al., 2013) conducted a pharmacokinetic study in 12 previously untreated postmenopausal women who each received 100 mg testosterone as a subcutaneous implant compounded by a local pharmacy in Cincinnati, Ohio.
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From page 126... ...
(2013) , a 2019 global consensus position statement, endorsed by multiple professional medical societies, recommended against the use of compounded testosterone in women (Davis et al., 2019)
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From page 127... ...
On day 22, 5 mg testosterone cream r estored both total and free testosterone levels to levels above and within the reference range, respectively, for premenopausal women. Example Study 3: Compounded Progesterone Cream Study Design and Results A randomized, crossover clinical trial was conducted in 10 post menopausal women to investigate the bioavailability of 80 mg of progesterone from compounded cream or gel applied daily to the inner thigh for 14 days (Du et al., 2013)
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From page 128... ...
TABLE 6–2 Progesterone Median Bioavailability Parameters Following Daily Application of 80 mg Progesterone Custom–Compounded 128 Cream or Gel Cream/ Gel Paired Cream Gel Differencea Median 25% Percentile 75% Percentile Median 25% Percentile 75% Percentile Median P Serum (n = 8) Cmax, ng/mL 0.71 0.53 1.42 0.59 0.42 0.93 0.331 0.0781 Tmax, ng/mL 9.00 5.00 14.00 8.00 3.50 10.00 1.00 0.6250 AUC0–24 h, ng h mL–1 12.39 10.31 19.68 8.32 6.92 12.98 5.00 0.0391 Whole blood (n = 8)
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From page 129... ...
. Example Study 4: Compounded Estradiol, Progesterone, Testosterone, and DHEA Lozenge Study Design and Results Investigators have evaluated the pharmacokinetics of compounded estradiol, progesterone, testosterone, and DHEA in an open-label study in six postmenopausal women following dosing with a lozenge using the transbuccal route of administration (Wren et al., 2003b)
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From page 130... ...
Of note, the study medication was prepared at a local pharmacy from a single batch to avoid variability in hormonal content and composition of the sublingual tablets. BIOAVAILABILITY OF TRADITIONALLY MANUFACTURED BIOIDENTICAL HORMONE THERAPY PRODUCTS As discussed in Chapter 8 of this report, patients may not be aware of or understand that FDA-approved bioidentical hormone therapy (BHT)
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From page 131... ...
Reference Study on the Bioavailability of FDA-Approved Bioidentical Estradiol and Progesterone Combination Product On October 29, 2018, FDA-approved Bijuva (estradiol and progesterone) capsules, the first FDA-approved BHT combination of estradiol and progesterone in a single, oral capsule for the treatment of moderate to severe vasomotor symptoms associated with menopause in women with a uterus.9 As part of the approval process, the pharmacokinetics and oral bioavailability of a capsule combining 17β estradiol and progesterone was compared to those of widely used and approved separate formulations of estradiol and progesterone coadministered to healthy postmenopausal women (Pickar el al., 2015)
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2000. A study to evaluate serum and urinary hormone levels following short and long term administration of two regimens of progesterone cream in postmenopausal women.
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From page 133... ...
2009. Com parison of salivary versus serum testosterone levels in postmenopausal women receiving transdermal testosterone supplementation versus placebo.
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From page 134... ...
2019. Evaluating urinary estrogen and progesterone metabolites using dried filter paper samples and gas chromatography with tandem mass spectrometry (GC-MS/MS)
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From page 135... ...
2003a. Transdermal progesterone and its effect on vasomotor symptoms, blood lipid levels, bone metabolic markers, moods, and quality of life for postmenopausal women.
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