Bioidentical Research Articles

476 Evaluation of the in vitro percutaneous absorption of progesterone, testosterone, estriol and estradiol topical compounded formulations

The safety, effectiveness and use of compounded bioidentical hormone replacement therapy has been questioned by the US Food and Drug Administration in the light of the recently published study report by The National Academies of Sciences, Engineering and Medicine. An in vitro study was conducted to evaluate the human skin percutaneous absorption of commonly prescribed bioidentical hormones using the Franz Skin Finite Dose Model. A topical compounded cream (VersaBase Cream) and gel (VersaBase Anhydrous HRT) were prepared for progesterone 100 mg/g, testosterone 1 mg/g, and estriol/estradiol [50%/50%] 2 mg/g. The 6 formulations were applied to the outer surface of ex vivo skin mounted in Franz diffusion chambers (9 tissues/formulation) to evaluate the total absorption, rate of absorption and skin content of the bioidentical hormones. The topical creams and gels for progesterone and testosterone exhibited similar mean flux profiles, characterized by a rise in skin percutaneous absorption to a peak at approximately 7 hrs (progesterone) and 5 hrs (testosterone) after dose application, followed by a slow decline in flux over time (24 hrs). The estrogens did not show a peak rise but instead a steady mean flux that increased slightly over the study time. Overall, the total absorption of the bioidentical hormones was higher for the topical gels in comparison to the creams. The total recovery (receptor medium, skin content and surface wash) of the bioidentical hormones varied from 87-97%. This study demonstrates that the bioidentical hormones penetrate through the skin (stratum corneum, epidermis and dermis) upon application of the topical compounded creams and gels. These results are important evidence to support the effectiveness of compounded bioidentical hormone replacement therapy since the in vitro model used has proven to accurately predict in vivo permeation kinetics.

Compounded bioidentical hormone therapy: new recommendations from the 2020 National Academies of Sciences, Engineering, and Medicine.

Bioidentical hormones have the exact same chemical and molecular structure as hormones that are produced in the human body. Bioidentical hormones are available as FDA-approved hormone formulations. Nonapproved custom-compounded preparations are marketed as bioidentical, but content is uncertain. The widespread use of compounded bioidentical hormone therapy despite the lack of evidence to support its safety and efficacy is concerning. This Practice Pearl highlights the 2020 recommendations from the National Academies of Sciences, Engineering, and Medicine regarding the use of compounded bioidentical hormones.

Low complication rates of testosterone and estradiol implants for androgen and estrogen replacement therapy in over 1 million procedures.

Background:Testosterone (T) deficiency (TD) in men and women and estrogen (E) deficiency (ED) in women increasingly affects the overall health and quality of life of patients. T implants have seen increased utilization over the past decade. We evaluated continuation rates and adverse events that occurred during T therapy by reviewing practitioner reported data on compressed human-identical T implants for the treatment of TD in both men and women collected over 7 years.Methods:This was a retrospective review of data collected prospectively from men and women from 2012 and 2019. Men who had the clinical syndrome of TD received subcutaneous T implant therapy. Women who presented with symptoms of TD and/or ED underwent T implant and/or estradiol implant therapy. The clinics spanned multiple specialties including obstetrics and gynecology, internal medicine, family practice, and urology. Data were entered into a secure, custom tracking App, using Azure App Services and MS SQL Database integrated with a proprietary dosing site and industry-leading Pharmacy Dispensing software (BioTracker®).Results:Over the 7 years, 1,204,012 subcutaneous implant procedures were performed for 376,254 patients; 85% of the procedures were performed in women. Of the women, 54% of were premenopausal, and 46% were postmenopausal. The overall continuation rate after two insertions was 93%. The overall complication rate was <1%. Most common secondary response reported was pellet extrusion, which was more common in men (<3%) than women (<1%).Conclusions:This study is the largest reported retrospective study to evaluate the continuation and complication rates of T pellet implants. The safety of subcutaneous hormone pellet implants in men and women appears to be better than other routes of administration of bioidentical hormone replacement therapy. Further investigations on short- and long-term benefits of this modality are ongoing and could expand the overall utilization of this method.

Hormone therapy for postmenopausal women

Hormone therapy is recommended for relief from hot flashes or night sweats in women younger than age 60 years or those who entered menopause within 10 years of seeking treatment. Hormone therapy also can reduce bone loss and the risk of fractures; offer a potential cardioprotective benefit; and alleviate the genitourinary symptoms of menopause, including dysfunction of the bladder and irritation of the vagina and vulva.For women with early menopause without contraindications, hormone therapy is recommended until at least the average age of natural menopause. Observational studies suggest that the risk of thromboembolism and stroke is lower with transdermal therapy than with oral hormone therapy. Compounded bioidentical hormone therapies that have not been approved by the Food and Drug Administration are not recommended owing to safety concerns. Hormone therapy is not recommended for primary or secondary prevention of coronary heart disease or dementia. Nonhormone therapies that have been shown to reduce hot flashes include low-dose selective serotonin-reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors, gabapentinoids, weight loss, hypnosis, and cognitive behavioral therapy. For women with only genitourinary symptoms, local vaginal hormone therapies are recommended.The treatment is not without its risks, including concerns about cognitive decline and breast cancer. More research is warranted, to determine the long-term benefits and risks of menopausal hormone therapy, to gauge the effects of prolonged use in women initiating therapy close to menopause, to inform the timing of and approach to hormone therapy discontinuation, and to answer additional unknowns. As scientists work to address these questions, technology can help identify women likely to benefit from hormone therapy. The MenoPro mobile app, backed by the North American Menopause Society, provides a free algorithm to flag the strongest candidates.

Bioidentical Oral 17β-Estradiol and Progesterone for the Treatment of Moderate to Severe Vasomotor Symptoms of Menopause

To review the efficacy, safety, and available literature regarding the novel combination bioidentical product Bijuva, or 17β-estradiol/progesterone (17β-E/P), for the treatment of moderate to severe menopausal symptoms in cisgender females with an intact uterus. Literature searches of both PubMed (1966 to October 2020) and Google Scholar were conducted using search terms including bioidentical, estradiol, progesterone, menopause, E2/P4, TX-001HR, and Bijuva. All articles with studies conducted in cisgender human females and in the English language were considered for review; 18 publications were included. In 1 phase 3 clinical study, 17β-E/P was proven to be effective at reducing the frequency and severity of vasomotor symptoms (VMS) at 12 weeks compared with placebo, and no cases of endometrial hyperplasia were observed over the 52-week safety study period. Menopausal women with an intact uterus were included in the study population. Concerns over content and safety of compounded bioidentical hormones have been raised by several professional societies. As women experience VMS of menopause, a desire for a Food and Drug Administration-regulated bioidentical combination product for the treatment of moderate to severe menopausal symptoms may be desirable. Given as a once-daily oral capsule at the dose of 1 mg estradiol/100 mg progesterone, 17β-E/P is approved for the treatment of VMS associated with menopause. 17β-E/P is a novel bioidentical product that is the first of its kind in the treatment of moderate to severe menopausal symptoms.

Postmenopausal Hormone Therapy-Local and Systemic: A Pharmacologic Perspective.

Every woman, if she lives long enough, will transition into menopause, and as the US population ages, women will be spending more time in a postmenopausal state than before. For postmenopausal women, the decision to initiate menopausal hormone therapy should be individualized. A thorough evaluation of the patient's cardiovascular, venous thromboembolic, cancer, and fracture risk should be considered along with the woman's quality of life. Hormone therapy exerts its therapeutic effects on vasomotor symptoms, the skeleton, and the genitourinary system independent of age since menopause and these benefits are lost once hormone therapy is stopped. Here we review the pharmacologic properties dose, formulation, mode of administration, timing of initiation, and duration of hormonal therapies in regard to optimizing benefit and minimizing risk to the patient. This discussion will focus on the effects of common hormonal therapies including estrogen (local and systemic), progesterone, estrogen receptor agonist/antagonist, and local dehydroepiandrosterone and include a brief review of compounded bioidentical hormone therapy.

Possibilities of using phytoestrogens in the treatment of menopausal syndrome

In the civilized world, there is a dilemma on how to relate to aging - to perceive it as a natural process characteristic of any living organism or to elevate it to the rank of a disease in order to try to develop methods of “treatment”. Age-related changes in a woman begin at about 40 years old and are associated with various hormonal changes. Often this stage in the life of the fair sex does not go unnoticed, it makes unpleasant corrections to the lifestyle with the need to change established habits and rules. Interestingly, in the era of information technology, women are not always sufficiently informed about the main age-related changes in their own body. The primary task of clinicians is to timely reveal the secrets of women’s health and help them adapt to the upcoming changes. Fluctuations in hormonal status are observed throughout a woman’s life. Contrary to the common misconception among women, it is completely incorrect to identify menopause with old age, because the hormonal function in women begins to fade long before the true aging. Climax is a multistage period of life, during which all systems of the female body adapt to the new conditions of estrogen deficiency. In the treatment of climacteric disorders hormonal therapy with synthetic analogues of female sex hormones is used. Only preparations of bioidentical hormones have a real protective effect on metabolic disorders, osteoporosis, cardiovascular complications, cognitive disorders. According to clinical recommendations, approaches to the treatment of menopausal disorders should be clearly customized to the identified risks and expected benefits. Choosing the optimal composition and regime of MHT allows to increase efficiency and minimize possible risks. Clinicians should not forget about situations where there are restrictions or contraindications to the use of MHT. The presence of absolute and relative contraindications to MHT, as well as widespread hormoneophobia in our country in women have led to the development of alternative methods of treatment of menopausal disorders.

The effect of bioidentical nanostructured progesterone in the in vitro culture of preantral follicles and oocyte maturation.

This study evaluated the effects of bioidentical nanostructured progesterone alone or in association with human chorionic gonadotropin (hCG) on the in vitro survival and development of preantral follicles (experiment 1) and oocyte maturation (experiment 2). Bioidentical hormones have a molecular structure identical with that of endogenous hormones; nanostructured substances refer to those reduced to a nanoscale. In experiment 1, fragments of goat ovarian tissue were cultured for 7 days in α-MEM+ alone or supplemented with nanoprogesterone (MEM+ + P4) or P4 and hCG (MEM+ + P4 + hCG). In experiment 2, two mediums of oocyte in vitro maturation (IVM) were compared. Medium 1 consisted of TCM 199+ + LH, and medium 2 consisted of TCM 199+ with nanoprogesterone and hCG. The MEM+ + P4 + hCG treatment showed the lowest percentage of follicular survival after 7 days of culture. MEM+ + P4 and MEM+ + P4 + hCG treatments showed higher percentage of follicular activation than MEM+. In experiment 2, there were no differences between mediums 1 and 2 for all endpoints evaluated. In conclusion, the addition of nanoprogesterone is advisable for in vitro culture of preantral follicles and oocyte maturation. However, the association of nanoprogesterone with hCG causes the cellular death of initial follicles but shows efficacy in IVM.

Compounded bioidentical HRT improves quality of life and reduces menopausal symptoms

Bioidentical hormone replacement therapy, a form of hormone balancing and treatment that uses hormones identical to the ones naturally produced by the body, is an effective and well-tolerated method of hormone replacement therapy. The Marion Gluck Clinic conducted a small-scale study to assess the effectiveness of compounded bioidentical hormone replacement therapy treatment protocols and their impact on the quality of life of women experiencing symptoms of the menopause. Quality of life was assessed by completing the Greene Climacteric Scale questionnaire before and after bioidentical hormone replacement therapy treatment. Statistical significance of the data was tested using a Student's two-tailed, paired t-test. The results demonstrated a significant improvement of 52% in quality of life after bioidentical hormone replacement therapy treatment. All 21 menopausal symptoms assessed were greatly reduced after BHRT treatment. Evidence is provided showing that bioidentical hormone replacement therapy, performed according to the Marion Gluck Clinic local clinical guidelines, improves quality of life and reduces menopause-associated symptoms in women. In addition, this pilot study paves the way for a future full-scale study, where the authors aim to assess quality of life and safety in a significantly larger number of women.

Understanding bioidentical hormones and their effect on quality of life

It is important to understand the functions of the body's hormones and the options available to make the right choices for use in treating the symptoms of menopause. Bioidentical hormones are compounds that have exactly the same chemical and molecular structure as endogenous human hormones. In contrast, non-bioidentical—or synthetic—hormones are structurally dissimilar from endogenous hormones. Although it has been available for years, bioidentical compounded hormone therapy has gained popularity only recently. This article highlights the main functions of these hormones and how hormone imbalances can affect a patient's quality of life, the importance of lifestyle and diet and what bioidentical hormones are, how they are prescribed, as well as the differences in treatment in different countries and the meaning of compounding.

Understanding bioidentical hormones and their effect on quality of life

It is important to understand the functions of the body's hormones and the options available to make the right choices for use in treating the symptoms of menopause. Bioidentical hormones are compounds that have exactly the same chemical and molecular structure as endogenous human hormones. In contrast, non-bioidentical—or synthetic—hormones are structurally dissimilar from endogenous hormones. Although it has been available for years, bioidentical compounded hormone therapy has gained popularity only recently. This article highlights the main functions of these hormones and how hormone imbalances can affect a patient's quality of life, the importance of lifestyle and diet and what bioidentical hormones are, as well as the differences in treatment in different countries and the meaning of compounding.

The role of bioidentical hormone replacement therapy in anti-aging medicine: a review of the literature.

The changes in skin and overall appearance that occur with increasing age can be partly attributed to declining hormone levels. While hormonal deficiencies are most commonly associated with postmenopausal females, males are also subject to age-related testosterone decline and may benefit from replacement of deficient hormones. However, great disparities exist between the recommendations of scientific societies and actual use of hormone supplements in aging patients. The purpose of this literature review is to discuss the role of hormones in the aging process of the skin, explain the safety profile of hormone replacement therapy, specifically discussing the superiority of bioidentical hormones, and highlight the benefits of hormone replacement in anti-aging of the skin. In summary, this literature review suggests that hormone replacement with bioidentical hormones is a safe and effective way to prevent skin aging.

Determination of estradiol and progesterone content in capsules and creams from compounding pharmacies.

Objectives:To analytically characterize the doses of estradiol and progesterone found in compounded combined forms of oral capsule and transdermal cream formulations, and determine the consistency of the hormone formulations within a batch.Methods:Prescriptions for combined estradiol/progesterone capsules (0.5 and 100 mg, respectively) and creams (0.5 and 100 mg/g, respectively) were sent to 15 custom-compounding pharmacies. Estradiol and progesterone levels were measured by radioimmunoassays. Hormone levels were measured in 2 capsules and 2 creams from each pharmacy; 10 capsules from 3 pharmacies; and top/middle/bottom layer of cream containers to assess consistency. The magnitude and sources of variation for the measurements were examined by analysis of variance models.Results:Thirteen pharmacies filled the prescriptions. Measured estradiol levels were 0.365 to 0.551 mg for capsules and 0.433 to 0.55 mg/g for creams, and progesterone levels were 90.8 to 135 mg for capsules and 93 to 118 mg/g for creams. Greater variations in estradiol levels were observed between pharmacies for estradiol in capsules than in creams; however, measured estradiol levels within pharmacies were more consistent in the capsules than the creams. Similar results were obtained for progesterone levels.Conclusion:The variations in estradiol and progesterone levels observed in compounded hormone therapy formulations justify concerns regarding risks as a result of variability, which have been outlined by The North American Menopause Society, the American College of Obstetricians and Gynecologists, and the US Food and Drug Administration (FDA) in their statements regarding compounded hormone use. These data support the need for an US FDA-approved bioidentical hormone therapy.Supplemental Digital Content is available in the textVideo Summary: Supplemental Digital Content 1.

Uterine bleeding rates with hormone therapies in menopausal women with vasomotor symptoms

Introduction: Bleeding and spotting are major reasons why women discontinue use of hormone therapy (HT) taken to treat menopausal vasomotor symptoms (VMS). The REPLENISH trial (NCT01942668) evaluated TX-001HR (TherapeuticsMD, Boca Raton, FL), a single oral capsule containing bioidentical 17β-estradiol (E2) and progesterone (P4), for treating moderate to severe menopausal VMS in women with a uterus; the 1 mg E2/100 mg P4 dose was recently approved as Bijuva™ by the US Food and Drug Administration (FDA; October 2018). This report compares the incidence of uterine bleeding with TX-001HR to other FDA-approved menopausal HT and unapproved compounded bioidentical HT (CHT).

Bioidentical hormone replacement therapy: implications for practice

In recent years, there has been a cultural shift towards greater acknowledgement of the effects of menopause on women's health, wellbeing and their relationships at both work and home, and an awareness of the very acute need for these symptoms to be monitored and addressed holistically as and when they change. No longer is it accepted that women should just ‘get on with it’, or feel helpless that there are few resources available to help them. As a result, there has been an increase in interest in bio-identical hormone replacement therapy (BHRT), especially following a greater media coverage of celebrities who have shared their own personal stories of this treatment. This has created a snowball effect, resulting in specialist clinics receiving an influx of new patients seeking cohesive and comprehensive advice. This article aims to explore some of the current advice relating to menopause and in particular the difference between HRT and BHRT. The authors will explore how this can impact the role of the aesthetic practitioner in supporting patients with symptoms relating to the menopause effectively.

Bioidentical hormone therapy in menopause: relevance in dermatology

Hormone replacement therapy has been shown to be effective in alleviating menopausal symptoms. However, its use is controversial owing to potential health risks, such as thromboembolism and cancer. Bioidentical hormone therapy has recently become popular as an alternative to conventional hormone replacement therapy. These bioidentical hormones have a molecular structure identical to endogenous hormones found in a woman's body. A claimed advantage of bioidentical hormone therapy is the compounding practice in order to individualize therapy depending on patient's own hormone levels and symptoms. However, there is no scientific evidence to assess the validity of these claims. Bioidentical hormone therapy has also been used by dermatologists for its anti-aging effects on the skin, but little is known about efficacy and side effects of bioidentical hormones in this field. This review illustrates the main purpose of bioidentical hormone therapy for dermatological uses and its potential side effects, serving as a tool for dermatologists when facing these patients.

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Hormone Therapy and Breast Cancer: Emerging Steroid Receptor Mechanisms.

Although hormone therapy is widely used by millions of women to relieve symptoms of menopause, it has been associated with several side-effects such as coronary heart disease, stroke and increased invasive breast cancer risk. These side-effects have caused many women to seek alternatives to conventional hormone therapy, including the controversial custom-compounded bioidentical hormone therapy suggested to not increase breast cancer risk. Historically estrogens and the estrogen receptor were considered the principal factors promoting breast cancer development and progression, however, a role for other members of the steroid receptor family in breast cancer pathogenesis is now evident, with emerging studies revealing an interplay between some steroid receptors. In this review, we discuss examples of hormone therapy used for the relief of menopausal symptoms, highlighting the distinction between conventional hormone therapy and custom-compounded bioidentical hormone therapy. Moreover, we highlight the fact that not all hormones have been evaluated for an association with increased breast cancer risk. We also summarize the current knowledge regarding the role of steroid receptors in mediating the carcinogenic effects of hormones used in menopausal hormone therapy, with special emphasis on the influence of the interplay or crosstalk between steroid receptors. Unraveling the intertwined nature of steroid hormone receptor signaling pathways in breast cancer biology is of utmost importance, considering that breast cancer is the most prevalent cancer among women worldwide. Moreover, understanding these mechanisms may reveal novel prevention or treatment options, and lead to the development of new hormone therapies that does not cause increased breast cancer risk.

Conjugated equine estrogen and medroxyprogesterone acetate are associated with decreased risk of breast cancer relative to bioidentical hormone therapy and controls.

ObjectiveBy the 1990s it became popular for women to use hormone therapy (HT) to ease menopause symptoms. Bioidentical estrogen and progesterone are supplements whose molecular structures are identical to what is made in the human body, while synthetic supplements are ones whose structures are not. After the Women’s Health Initiative found that the combined use of the synthetics conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increased breast cancer risk, prescriptions for synthetic HT declined considerably. Since then there has been an increased interest in bioidentical HT; today there are a plethora of websites touting their benefits. However, no peer-reviewed articles support these claims. We performed a retrospective study with the objective of verifying the hypothesis that bioidentical HT is associated with decreased breast cancer risk than CEE & MPA.MethodsWe searched The Northwestern Medicine Enterprise Data Warehouse for women who initiated HT use after age 50. Women who did not take any HT drug after age 50 served as controls. Nine HT protocols were investigated for breast cancer risk.ResultsSignificant results include CEE Alone is associated with decreased breast cancer risk (HR = 0.31), Other Synthetic Estrogen Alone is associated with increased breast cancer risk (HR = 1.49), Bioidentical Estrogen Alone is associated with decreased breast cancer risk(HR = 0.65), CEE & MPA is associated with reduced breast cancer risk (HR = 0.43), and CEE & MPA is associated with reduced breast cancer risk relative to Bioidentical Estrogen & Progesterone (HR = 0.25).DiscussionOur results indicate CEE & MPA is superior to bioidentical HT as far as breast cancer risk. Furthermore, this combination is associated with decrease of breast cancer risk, contrary to previous findings. Additional retrospective studies are needed to confirm our results.

P-334 - Brain nutrition, aging and neuroplasticity

Neuroplasticity allows the neurons in the brain to compensate for injury and disease and to adjust their activities in response to new situations or to changes in their environment. The aging brain can adapt through cellular defences mechanisms, such as redox capacity, DNA repair, release of neurotrophins (BDNF, IGF-1), promotion of neurogenesis and the capability of the dendrites and synapses to change in response of the environmental stress. The brain's perfect immunity regulation by the microglia and the central nervous system's anti-oxidant capacity enhancement depends on several concepts, including the best nutritional foods and supplements, hormones, physical activity and learning procedures. The aim of this talk is to reveal the biochemical and immunological mechanisms behind the brain aging in order to prevent the neurodegenerative diseases and stimulate the neuroplasticity with the use of dietary functional substances, natural immune-modulatory molecules and bio-identical hormones.