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Context
Custom-compounded bioidentical hormone therapy (HT) has become widely used in current endocrine practice, which has led to unnecessary risks with treatment.
Objective
This scientific statement reviews the pharmacology and physiology of popular compounded hormones and the misconceptions associated with these therapies. The hormones reviewed...
Contexts in source publication
Context 1
... 3 is the major metabolically active thyroid hormone that binds to thyroid hormone receptors and affects tis- sues. The human thyroid gland secretes approximately 101 mcg of T 4 and 6 mcg of T 3 daily into the circulatory system (a T 4 to T 3 secretion ratio of about 17:1); the pe- ripheral conversion of T 4 to T 3 by deiodinase enzymes (predominantly in the liver) (11) accounts for another 20 mcg of circulating T 3 (Figures 3 and 4). The ratio of T 4 to T 3 in the circulation is approximately 4:1. Researchers estimate that 80% of brain T 3 is the product of the local conversion of T 4 to T 3 by brain deiodinase 2 (D2), whereas only 20% of brain T 3 comes from the circulatory system. Therefore, in humans, it appears that the thyroid gland functions mainly to produce a sufficient supply of the cir- culating prohormone T 4 and that deiodinases serve to provide appropriate intracellular T 3 concentrations by regulating the conversion of local T 4 to T 3 in a highly tissue-specific manner (12,13). This ability of peripheral tissues, for the most part, to regulate T 4 to T 3 conversion, substantially weakens the rationale for individualized dos- ing of customized or compounded combinations of T 4 and T 3 ...
Context 2
... identified the active principle in thyroid ex- tract in 1915 (6) and named the chemical structure T 4 in 1927 ( Figure 3) (7). The levothyroxine (LT 4 ) isomer is the form that is synthesized in the thyroid gland and secreted into the circulation. Patients had trouble absorbing LT 4 and racemic T 4 mixtures (LT 4 and dextrothyroxine) but had much better success absorbing oral preparations of the salt, sodium LT 4 ...
Context 3
... hormone prepara- tions that are currently available include synthetic LT 4 (eg, Synthroid, Levoxyl, Unithroid, Tirosint) and generic LT 4 , synthetic LT 3 (eg, Cytomel) and generic LT 3 , desiccated thyroid products (eg, Armour Thyroid, Westhroid, Na- ture-Throid, Prothroid, Novothyral, Thyreotom, Thyro- lar-3, and Diotroxin), and compounded preparations (202). Synthetic LT 4 preparations contain only LT 4 , and the T 4 molecule in these preparations is identical to LT 4 that the human thyroid gland produces (Figure 3). Simi- larly, synthetic LT 3 preparations contain pure LT 3 , which is identical to that produced by the human thyroid gland. Drug manufacturers make desiccated thyroid prepara- tions by drying and powdering pig or cow thyroid glands. The most common form of desiccated thyroid, Armour Thyroid, comes from pig thyroid extract. Desiccated thy- roid products consist of about 80% T 4 and 20% T 3 (ap- proximately a 4:1 ratio of T 4 to T 3 ). The hormone content and the T 4 to T 3 ratio may vary in desiccated thyroid products, depending on the brand and whether they are of porcine or bovine origin ...
Context 4
... identified the active principle in thyroid extract in 1915 (6) and named the chemical structure T 4 in 1927 ( Figure 3) (7). The levothyroxine (LT 4 ) isomer is the form that is synthesized in the thyroid gland and secreted into the circulation. ...
Context 5
... 3 is the major metabolically active thyroid hormone that binds to thyroid hormone receptors and affects tissues. The human thyroid gland secretes approximately 101 mcg of T 4 and 6 mcg of T 3 daily into the circulatory system (a T 4 to T 3 secretion ratio of about 17:1); the peripheral conversion of T 4 to T 3 by deiodinase enzymes (predominantly in the liver) (11) accounts for another 20 mcg of circulating T 3 (Figures 3 and 4). The ratio of T 4 to T 3 in the circulation is approximately 4:1. ...
Context 6
... hormone preparations that are currently available include synthetic LT 4 (eg, Synthroid, Levoxyl, Unithroid, Tirosint) and generic LT 4 , synthetic LT 3 (eg, Cytomel) and generic LT 3 , desiccated thyroid products (eg, Armour Thyroid, Westhroid, Nature-Throid, Prothroid, Novothyral, Thyreotom, Thyrolar-3, and Diotroxin), and compounded preparations (202). Synthetic LT 4 preparations contain only LT 4 , and the T 4 molecule in these preparations is identical to LT 4 that the human thyroid gland produces (Figure 3). Similarly, synthetic LT 3 preparations contain pure LT 3 , which is identical to that produced by the human thyroid gland. ...
Citations
... At present, no publications in the peer-reviewed literature demonstrate compounded creams, pills, or pellets to be safer, more efficacious, or less likely to cause adverse events compared to FDA-approved products (12,13,19,40,41). A properly designed non-inferiority study of a cBHT product vs. a biosimilar FDA-approved product is needed to codify claims made in advertising. ...
Compounded bioidentical hormone therapy (cBHT) for menopausal symptoms maintains popularity in western countries despite the availability of hormone products in different formulations and dosages produced by pharmaceutical companies with federal oversight. Akin to many populist therapeutic trends in the history of medicine, cBHT advocates tend to capitalize on consumer fears about existing FDA-approved hormone treatments. Unsubstantiated, exaggerated, or outright false claims are commonplace in promoting cBHT. Given these elements, the basic elements of pharmaceutical messianism continue to drive the cBHT movement.
... 55,42 cBHRT are not recommended by menopausal and endocrine societies because they are not properly regulated and have not been adequately tested for efficacy and safety. 42,55,56 Regarding menopausal skin treatment, although some small studies have found that cBHRT can increase skin hydration and reduce skin atrophy, 57 no large appropriately designed studies have yet been conducted. ...
Menopause is a state of estrogen deficiency that affects numerous estrogen-dependent tissues in the female body. Skin is one of the most affected organs. Many consider menopausal skin changes to be merely an aesthetic problem; however, they can significantly affect women’s quality of life. Currently, there are no approved effective treatments to prevent or alleviate skin changes associated with estrogen deficiency. Standard systemic hormone replacement therapy used to treat menopausal symptoms may be effective to some degree for skin treatment. In addition, compounded bioidentical hormone replacement therapy, selective estrogen receptor modulators, and phytoestrogens could also be used for skin treatment, although this is only hypothetical due to lack of data. Many questions therefore remain unanswered. On the other hand, topical, low-dose estrogen that would act only on the skin without systemic effects could be a possible option, as could be skin-only acting topical phytoestrogens. Such topical products without systemic effects could play a role in the treatment of menopausal skin. However, they are not currently approved because there is insufficient data on their safety and efficacy. A healthy lifestyle could have a positive effect on the menopausal skin. In this review, we provide an overview of the characteristics of menopausal skin, an outlook on the future treatment of menopausal skin with estrogens and other approaches, and the associated controversies and speculations. Overall, the importance of menopausal skin changes should not be neglected, and high-quality research is needed to gain new insights into the treatment of menopausal skin.
... The most common symptoms include hot flashes, night sweats, emotional lability, poor concentration, and sleep disturbance; these can range from mild to severe. Vasomotor symptoms, or hot flashes, are reported by more than 70% of women as they go through menopause and may persist for many women all over the world [8][9][10][11][12][13][14]. There are three types of hormone replacement therapy (HRT): (a) conventional HRT; (b) Food and Drug Administration (FDA)-approved bioidentical hormone therapy (HT); and (c) compounded bioidentical hormone therapy (CBHT) [12,14]. ...
... The Endocrine Society has defined compounded bioidentical hormones as: "compounds that have the same chemical and molecular structure as hormones that are produced in the human body" [8,9,12]. Anyhow, the term "bioidentical hormone" does not have a unified and structured definition; in fact, this terminology often confuses clinicians and patients. ...
... Since the WHI trial, a substantial group of postmenopausal women using HT decided with their treating physicians to switch from synthetic hormones to bioidentical HT (CBHT). During the past 2 decades, CBHT has become more and more popular in the USA and Europe [8]. Some physicians and patients determined that CBHT therapy was more appropriate and suitable [28]. ...
Background: The role of hormonal replacement therapy in menopause is under debate. The premature closure of the Women’s Health Initiative (WHI) study in 2002 is still a source of concern among treating physicians. Objectives: The interest in alternatives to conventional hormone therapy has significantly increased. The adoption of personalized steroid hormone galenic preparations, formulated by compounding pharmacies, has recently spread. Methods: In June 2023, an extensive literature search was conducted by different authors to identify relevant studies in various databases (MEDLINE, Embase, Pubmed, and Cochrane). The studies that met the inclusion and exclusion criteria were further analyzed, and relevant data were extracted and analyzed for each paper. Any discrepancies between the investigators were resolved through a consensus approach. Outcomes: The primary outcomes observed included the clinical utility of CBHT. This study reviewed the current evidence on the utility of compounded bioidentical hormones, concluding that improving knowledge and awareness of bioidentical hormones is necessary to consider their use in clinical practice. Conclusion and Outlook: These formulations might provide effective options to best tailor therapies to each patient.
... To treat menopausal symptoms, combined estrogen-progestin therapy (in women with an intact uterus) or estrogen-only therapy (in women who have undergone a hysterectomy) is currently approved as menopausal hormone therapy (MHT) [19]. Current MHT recommendations are largely governed by the "timing hypothesis", which posits that MHT is effective only when administered near the start of menopause in younger postmenopausal women [20]. ...
Frailty is a multidimensional clinical syndrome that increases the risk of adverse health outcomes. Previous studies have reported a close link between menopause and frailty. Combined estrogen–progestin therapy (or estrogen-only therapy in women who have undergone a hysterectomy) is currently approved as a menopausal hormone therapy (MHT) to treat menopausal symptoms. Despite increasing evidence of the importance of sex hormones in the development of frailty, very few studies have investigated the association between MHT and frailty. A cross-sectional evaluation was conducted using population-based survey data known as the Korea National Health and Nutrition Examination Survey (KNHANES IV-V, 2008–2012). The KNHANES data provided variables that were used to construct a 51-item frailty index (FI). The number of study population, only including postmenopausal women, was 7823 women, and their mean age was 62.51 years (range 32–80 years). Approximately 40% of them had graduated from middle school or higher, 45% lived in metropolitan statistical areas, and 5% were recipients of the national Medical Aid. The mean age at menopause was 48.66 years (range 30–62 years). Overall, the mean FI value was 0.15, and the prevalence of MHT was 13.23%. Findings from multiple regression analysis using the inverse probability of treatment weighting showed that a treatment duration of more than 2 years and up to 5 years, age at first treatment between 50 and 59 years, and MHT initiation 3 to 6 years after menopause were all negatively associated with frailty (p < 0.05). Further studies are needed to confirm these findings using prospective data.
... Bioidentical hormones are man-made hormones derived from plants, often soy and yams, that are chemically identical to those the human body produces. As such, they bind to the estrogen and testosterone receptors in the same way as women's endogenous hormones have throughout their lives [24]. The U.S. FDA has approved some forms of manufactured bioidentical hormones, including bioidentical estrogens and progesterone. ...
Hormone replacement therapy continues to be a controversial topic in medicine, with certain narratives regarding safety concerns that are not scientifically established in peer-reviewed literature. These negative narratives, specifically undermining the use of testosterone in women, have caused women to remain without any Food and Drug Administration (FDA)-approved testosterone therapies, while more than 30 FDA-approved testosterone therapies are available for men in the United States. This has resulted in millions of women suffering in silence with very common symptoms of perimenopause and menopause that could easily be addressed with the use of testosterone. There is growing evidence to support the use of physiologic doses of testosterone for sexual function, osteoporosis prevention, brain protection, and breast protection. The safety of testosterone use in women has been evaluated for the past 80 years. A recent publication on the complications of subcutaneous hormone-pellet therapy, looking at a large cohort of patients over 7 years, demonstrated long-term safety. In addition, there have been two large long-term peer-reviewed studies showing a significant reduction in the incidence of invasive breast cancer in women on testosterone therapy. Perhaps it is time for the FDA to consider approving products that would benefit testosterone-deficient women.
... However, pills, gels, and suppositories, which consist of several hormones -estradiol, estrone, estriol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) -are gaining practical application. Such complex hormonal systems require careful monitoring and prescription only by a medical professional [39,42]. ...
It is known that a deficiency of estrogens of any origin (physiological menopause, surgical removal of the ovaries, etc.) accelerates the aging processes of both the body in general and the skin in particular in women. Studies of the morphometric properties of skin caused by estrogen-deficient states may help in the development of more effective regenerative medicine approaches aimed at treating and preventing age-related skin changes. The purpose of the study is to determine the morphological changes in the skin of young and old SBA/Сa mice with estrogen deficiency on the ovariectomy model. Materials and methods. Skin samples from young (4 months) and old (16 months) mice two months after ovariectomy were compared with age-matched sham-operated mice. The thickness of the epidermis and dermis, the number of hair follicles, and sebaceous glands were determined on histological samples of the skin. Results and discussion. It was shown that the thickness of the epidermis was significantly smaller both in the group of young and in the group of old ovariectomized mice compared to the thickness of the epidermis of the control group of animals of the corresponding age. A significant increase in the thickness of the dermis was found in the group of young ovariectomized mice in comparison with the thickness of the dermis in the young control group, however, in the group of old ovariectomized mice, the thickness of the dermis did not differ significantly compared to the age-matched control group. No significant differences were found in the number of sebaceous glands and hair follicles in the studied groups. Conclusions. Ovariectomy, as a model of artificial estrogen deficiency, is accompanied by significant changes in the epidermis in young and old animals and the dermis in young ovariectomized animals, without affecting the number of sebaceous glands and hair follicles.
... The study of the anatomy, physiology and biochemistry of the thyroid gland has steadily increased due to the fact that thyroid disease has moved into the category of medical and social problems all over the world according to reports. authors (Santoro et al. 2016) [2]. ...
... The study of the anatomy, physiology and biochemistry of the thyroid gland has steadily increased due to the fact that thyroid disease has moved into the category of medical and social problems all over the world according to reports. authors (Santoro et al. 2016) [2]. ...
This study was carried out to study the peculiarities of the topography, the macrostructure and the analysis of the structural and functional organization patterns of the parenchyma of the thyroid gland of dairy cows (local breed from the Souk Ahras region, Algeria). A complex of macroscopic and histological techniques was used, as well as immunohistochemical staining of thyroid gland sections to identify localization characteristics of thyrocyte populations in the parenchyma. The macroscopic data was highly variable, including the length, width and thickness of the gland, which appear to be greatly increased during the winter period. The parenchyma was characterized by a spongy-like structure in the form of a set of partially concave lobules, surrounded by a framework of connective tissue are represented by a capsule and a trabecular formation in the form of septa, the lobular structure is positioned from diffusely containing follicles rich in thyrocytes and bases by a complex of blood vessels. The amount of thyrocytes strongly depended on the time of the season. The structure of the parenchyma of the thyroid glands of cows was not absolutely unique, as in other species of mammals, subdivided into specialized cell areas that are connected to follicles. The histometric characteristics of the follicles show that there is a secretion activity of the very important hormones of T3 (tri-iodothyronine) and T4 (tetra-iodothyronine) during the summer period, has been proved by the results carried out by ELISA of the assay of these hormones.
... La determinación apropiada de las hormonas en saliva depende del método de obtención de la muestra, y su disrupción provoca resultados erróneos, debido a que su extracción no es un método «sencillo», como se reporta en la literatura. Dentro de la cavidad oral la presencia de las enzimas 17-hidroxiesteroide oxidorreductasa (encargada de la biotransformación de androstenediona a T) y 11 β-hidroxiesteroide deshidrogenasa tipo II (cortisona a cortisol) provocan una ligera disminución en saliva comparado con las concentraciones de hormonas libres séricas 11,25,26 . Otra limitante es que debe garantizarse la ausencia de residuos alimenticios o gingivales, por medio del lavado dental 30 minutos antes de la toma de saliva, seguido de un adecuado enjuague bucal con agua de por lo menos 10 minutos con recolección salival por al menos 2 minutos 25 . ...
... Son esteroides C18 que se producen principalmente en la granulosa del ovario y en los que se incluyen E1, E2 y E3 11,29 . En la etapa reproductiva la concentración de estrógeno oscila entre 30 y 300 pg/ml y puede ser tan alta como 2,000 pg/ml en el embarazo. ...
... Hoy se dispone de PM para soporte lúteo en presentación oral y vaginal aprobada por la FDA 11 . La PG tópica es desaconsejable debido a la carencia de enzimas apropiadas para convertir prehormonas en PG biológicamente activa. ...
... Використання засобів сВHT жінками викликає особливе занепокоєння з огляду на наступні ризики: захист ендометрія при застосуванні комбінацій естрогени/гестагени; ризики раку молочної залози, тромбоемболічні ризики, протективний вплив на щільність кісткової тканини (не доведений). Терапія сВHT є вкрай небезпечною через відсутність даних щодо дози (у мг, г або Од), методів визначення активності цих гормональних речовин, режиму дозування, тривалості прийому та відсутність можливості дострокової відміни гормонального засобу (пелет) [59][60][61]. ...
The document was approved at an expanded meeting of the Ukrainian Society of Gynecological Endocrinology with the involvement of all board members and representatives of the Association of Obstetricians-Gynecologists of Ukraine, the Association of Pharmacologists of Ukraine, the Association of Anesthesiologists of Ukraine, as well during the Third Ukrainian School of Gynecological and Reproductive Endocrinology with international participation ISGE 19–20.03.21.
The COVID-19 pandemic has significantly impacted medical practice, in terms of organizational and clinical practices, posing a number of complex and contradictory challenges for professionals.
This document is the result of the systematization of scientific data available by March 2021 and recommendations of international medical and specialized professional societies on controversial clinical issues in gynecological practice caused by the COVID-19 pandemic, as well as certain issues of safety and ratio of using hormonal drugs. The involvement of experts from professional associations of the obstetric and gynecological field, pharmacology, anesthesiology and vascular surgery and phlebology in the working group made it possible to formulate clinically justified provisions of the position.
The position includes three thematic sections: “On the use of estrogen-containing combined hormonal contraceptives (CHC) during the COVID-19 pandemic”; “On the use of menopausal hormone therapy (MHT) during the COVID-19 pandemic”; “On the issue of unregistered compounded bioidentical hormones”.
At the beginning of each thematic section, the main conclusions of the consensus position of professional medical associations are presented. According to the data available by March 2021, there is no reason to limit the use of CHC or MHT in healthy women (currently not having COVID-19). The question of CHC or MHT discontinuing or switching to other forms by women with COVID-19 should be decided depending on the severity of the disease, the total set of risk factors for thromboembolic complications and other individual characteristics of the clinical situation. Further research will provide elaboration of more detailed algorithms. Physicians need to be vigilant about the safety of compounded Bioidentical Hormonal Therapy (cBHT) in any dosage form (including pellets), especially during the COVID-19 pandemic, given the unexplored systemic effects and therefore the potential risks. Preference should be given to officially licensed medicinal products with a well-studied safety profile and clinical effects, the use of which is authorized by doctor's prescription and supported by clinical protocols and guidelines.
... However, in popular culture, the term refers to the use of custom-compounded multihormone regimens (pills, gels, sublingual tablets, or suppositories) with dose adjustments based upon serial hormone monitoring. The hormones most-commonly compounded are estradiol, estrone, estriol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) [75,76]. ...
Estrogen is a pivotal signaling molecule; its production is regulated by the expression of the aromatase (CYP19A1) gene from ovarian and peripheral tissue sites, and it is transmitted via estrogen receptors to influence many important biological functions. However, the narrative for this overview focuses on the decline of 17β-estradiol levels from ovarian sites after menopause. This estrogen-deficient condition is associated with a dramatic reduction in skin health and wellness by negatively impacting dermal cellular and homeostatic mechanisms, as well as other important biological functions. The changes include loss of collagen, elastin, fibroblast function, vascularity, and increased matrix metalloproteinase(s) enzymatic activities, resulting in cellular and extracellular degradation that leads to dryness, wrinkles, atrophy, impaired wound healing/barrier function, decreased antioxidant capacity [i.e., defense against reactive oxygen species (ROS) and oxidative stress], decreased attractiveness and psychological health, and increased perception of aging. While topical estrogen may reverse these changes, the effects of today’s low-dose systemic hormone treatments are not well established, raising the need for more concentrated local administration of hormones or newer cosmeceutical agents such as selective estrogen receptor modulators (SERMs), including phytoestrogens that have become major active ingredients for skin care products, especially when addressing estrogen-deficient skin. Two example compounds are presented, an analog of resveratrol (i.e., 4′-acetoxy resveratrol) and the isoflavonoid equol, both of which are involved in a variety of biochemical/molecular actions and mechanisms, as demonstrated via in vitro and clinical studies that enhance human dermal health, especially in estrogen-deficient skin.
