The Clinical Utility of Compounded Bioidentical Hormone Therapy A Review of Safety, Effectiveness, and Use (2020) / Chapter Skim
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4 Reproductive Steroid Hormones: Synthesis, Structure, and Biochemistry
4 Reproductive Steroid Hormones: Synthesis, Structure, and Biochemistry
Pages 75-90
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. The remaining sections of the chapter will focus on steroid hormones, define what is meant by the term bioidentical steroid hormones, and provide a high-level overview of the structure and biochemistry of the hormones commonly used in compounded bioidentical hormone therapy (cBHT)
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A bioidentical hormone is a term that describes a hormone that is chemically and structurally identical to those produced by the human body, with the implication that an identical chemical structure translates to a physiologic response identical to that of the endogenous hormone. Biodentical i hormones may be synthesized from plant or animal sources, or completely chemically synthesized (American Chemical Society and Sociedad Química de México, 1999; Wang et al., 2011)
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. Exogenous Sources of Bioidentical Hormones Exogenous source material, including plants, must be processed chemically to create bioactive hormone products that the human body's endogenous hormone receptors can recognize.
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Conclusion 4-1 Use of the term bioidentical is a source of confusion. Bioidentical means that the hormone's chemical structure is identical to that of a hormone occurring naturally in the body, and consequently implies its biologic activity is identical to that of a hormone occurring naturally in the body.
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Ovaries are the main source of E1. E1 is a minor hormone in the female reproductive cycle, though it plays a larger physiological role following menopause.
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In its activated complex, it promotes the transcription of genes involved in the female reproduction system and in producing secondary sex characteristics. Estradiol cypionate can also serve as a prohormone that the body converts readily into the endogenous form, estradiol (NLM, 2020a)
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is derived from E1 and E2 and is primarily synthesized within the placenta during pregnancy. It is a far less potent estrogen than E2, and with little circulating in nonpregnant women, it serves as a minor female sex hormone (Cui et al., 2013; Keller, 1974)
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(See Figure 4-8 for the chemical structures of testosterone, testosterone cypionate, and testosterone propionate.)
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Dehydroepiandrosterone DHEA is an endogenous hormone produced in the adrenal glands and brain. In addition to its own role as a bioactive hormone and neurosteroid, circulating DHEA serves as an important precursor for estrogens and testosterone in postmenopausal women (see Figure 4-9)
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. In classical mechanisms of hormone action, hormones cross through the plasma membrane and d irectly bind to and act through intracellular nuclear receptors to regulate ranscription of thousands of genes.2 Rapid steroid hormone signaling t o ccurs through steroid receptors residing in the cell membrane, which when a ctivated by hormones, can initiate downstream signaling to stimulate e nzymes, amplify effects of other activated receptors, or directly influence the transcription of various genes.
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. Steroid receptor isoforms, when bound to their respective steroid hormones, can produce different tissue-specific gene expression patterns and often mediate distinct functional effects.
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. A major source of variability in hormone signaling is the genomic context, resulting in variation in the structure and activity of hormone receptors and the enzymes involved in biosynthesis of the steroid hormones themselves (Fuentes and Silvera, 2019)
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Conclusion 4-2 Circulating hormone levels are not necessarily predictive of biological activity because steroid hormones, including those used in compounded bioidentical hormone therapy preparations, produce highly variable responses that are dependent on a number of factors, including genetic background, prior exposure to steroid hormones, and environmental and lifestyle factors. REFERENCES American Chemical Society and Sociedad Química de México.
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2003. Androgen receptor isoforms ar-a and ar-b display functional differences in cultured human bone cells and genital skin fibroblasts.
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2011. Differences in verbal memory performance in postmenopausal women receiving hormone therapy: 17β-estradiol versus conjugated equine estrogens.
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