Hormone Formulations Research Articles

Enhancing blueberry drought resilience: ABA and MeJA hormonal formulations unveil water-saving strategies

Enhancing blueberry drought resilience: ABA and MeJA hormonal formulations unveil water-saving strategies

Impact of hormone replacement therapy on cardiovascular risk in patients with hypothyroidism: a systematic review

Hypothyroidism, which is developed in 4-10 % of the population, and subclinical hypothyroidism found in more than 10 % of people which are highly associated with cardiovascular pathophysiology at some level. Hypothyroidism, which is the most frequent endocrine disorder with a lack of enough thyroid hormones, presents a wide range of cardiovascular complications, including coronary artery disease, heart failure, and dyslipidemia. Thyroid hormone replacement therapy, particularly levothyroxine (LT4), continues to be the central management of hypothyroidism, which aims to restore euthyroidism and other cardiac comorbidities as well as relieving symptoms. Nonetheless, the complex interworking of thyroid function and cardiovascular health requires a detailed clarification of the processes associated with disease development and drug therapy. Hypothyroidism triggers a chain of cardiovascular alterations such as aberrant lipid metabolism, endothelial dysfunction, and lessened cardiac contractility primarily by lowering the thyroid hormone level. Besides, these modifications eventually lead to raised rates of atherosclerosis, myocardial infarction, and heart failure. LT4 replacement therapy achieves normalization of hyperthyroidism with the replacement of thyroid hormone deficiency, which restores the cardiovascular system to normal by doing so. LT4 modulates lipid metabolism, improves endothelial function, and stimulates myocardial contractility via several different mechanisms. LT4 therapy acts on systemic inflammation and oxidation to accentuate the protective effects of the cardiovascular system. Apart from this, there is an increasing awareness about the use of new thyroid hormone formulations, like LH4, in the therapy of hypothyroidism. LH4, the thyromimetic compound, demonstrated a similar binding affinity at the thyroid hormone receptor as T3 (triiodothyronine) but with better tissue selectivity and more metabolic stability. Clinical trials have proven the potency of LH4 in lowering symptoms of hypothyroidism, for example, fatigue, weight gain which are leading cause of cardiovascular disorders. LH4 administration has been safe for up to six months, and only mild adverse effects have been reported when it is used more than a year.

Update on the use of long-acting growth hormone in children.

After extensive research and many years of waiting, long-acting growth hormone (LAGH) formulations have finally become a reality in clinical practice and emerge as a potential solution to address the challenges of daily injections of recombinant human GH (rhGH). In this review, we present a brief history of the development of LAGH and provide a critical analysis of the existing literature on the five LAGH available and approved to date for treatment in children. In clinical trials, LAGH therapy has shown noninferiority compared with daily rhGH therapy in promoting linear growth in children with GH deficiency, with similar rates of adverse events. In the real world, many questions still need to be answered, such as whether a specific group of patients will benefit most from the weekly injection, whether compliance will be better compared with daily rhGH, whether long-term efficacy, monitoring and safety profile will be the same for the different LAGH compounds, and whether the cost-effectiveness will justify their use in different settings.

Progestins and breast cancer hallmarks: The role of the ERK1/2 and JNK pathways in estrogen receptor positive breast cancer cells

Progestins used in hormonal contraceptives and menopausal hormone therapy (MHT) have been linked to increased breast cancer risk. Whether the association holds for all progestins is unclear and the underlying mechanisms remain poorly understood. We directly compared the effects of four progestins (medroxyprogesterone acetate (MPA), norethisterone acetate (NET-A), levonorgestrel (LNG) and drospirenone (DRSP)) to each other and the natural progestogen progesterone (P4) on selected cancer hallmarks. To provide mechanistic insight into these effects, we assessed the role of the progesterone receptor (PR), and the extracellular signal-related kinase (ERK1/2) and c-Jun N terminal (JNK) signaling pathways. We showed that the increased proliferation of the luminal T47D breast cancer cell line by P4 and all progestins, albeit to different extents, was inhibited by PR knockdown and inhibition of both the ERK1/2 and JNK pathways. While knockdown of the PR also blocked the upregulation of MKI67 and CCND1 mRNA expression by selected progestogens, only a role for the ERK1/2 pathway could be established in these effects. Similarly, only a role for the ERK1/2 pathway could be confirmed for progestogen-induced colony formation, whereas both the ERK1/2 and JNK pathways were required for cell migration in response to the three older progestins implicated in the etiology of breast cancer, MPA, NET-A and LNG. Together our results show that all the progestins elicit their effects on cell proliferation via a mechanism requiring the PR, ERK1/2 and JNK pathways. While the ERK1/2 and JNK pathways are also required for increased cell migration by the older progestins, only a role for the ERK1/2 pathway could be established in their effects on colony formation. Notably, the cytoplasmic PR was not needed for activation of the ERK1/2 pathway by the progestogens. Given that DRSP showed significantly lower proliferation than MPA and NET-A, and that it had no effect on breast cancer cell migration and colony formation, hormonal formulations containing the newer generation progestin DRSP may provide a better benefit/risk profile towards breast cancer than those containing the older generation progestins.

Novel therapies for growth disorders.

As we continue to understand more about the complex mechanism of growth, a plethora of novel therapies have recently been developed that aim to address barriers and optimize efficacy. This review aims to explore these novel therapies and provide a succinct review based on the latest clinical studies in order to introduce clinicians to therapies that will soon constitute the future in the field of short stature. Conclusion: The review focuses on long-acting growth hormone formulations, a novel growth hormone oral secretagogue, novel treatments for children with achondroplasia, and targeted therapies for rare forms of skeletal dysplasias. What is Known: • Recombinant human growth hormone has been the mainstay of treatment for children with short stature for years. • Such therapy is not always effective based on the underlying diagnosis (e.g achondroplasia, Turner syndrome). Compliance with daily injections is challenging and can directly affect efficacy. What is New: • Recent development of long-acting growth hormone regimens and oral secretagogues can overcome some of these barriers, however several limitations need to be taken into consideration. • Newer therapies for achondroplasia, and other rare forms of skeletal dysplasias introduce us to a new era of targeted therapies for children with short stature. Clinicians ought to be aware of pitfalls and caveats before introducing these novel therapies to every day practice.

Guideline No. 315: Prevention of Ovarian Hyperstimulation Syndrome

Summary Statements1.The particular follicle-stimulating hormone formulation used for ovarian stimulation does not affect the incidence of ovarian hyperstimulation syndrome. (I)2.Coasting may reduce the incidence of severe ovarian hyperstimulation syndrome. (III)3.Coasting for longer than 3 days reduces in vitro fertilization pregnancy rates. (II-2)4.The use of either luteinizing hormone or human chorionic gonadotropin for final oocyte maturation does not influence the incidence of ovarian hyperstimulation syndrome. (I)5.There is no clear published evidence that lowering the human chorionic gonadotropin dose will result in a decrease in the rate of ovarian hyperstimulation syndrome. (III)6.Cabergoline starting from the day of human chorionic gonadotropin reduces the incidence of ovarian hyperstimulation syndrome in patients at higher risk and does not appear to lower in vitro fertilization pregnancy rates. (II-2)7.Avoiding pregnancy by freezing all embryos will prevent severe prolonged ovarian hyperstimulation syndrome in patients at high risk. (II-2)8.Pregnancy rates are not affected when using gonadotropin-releasing hormone (GnRH) agonists in GnRH antagonist protocols for final egg maturation when embryos are frozen by vitrification for later transfer. (II-2) Recommendations1.The addition of metformin should be considered in patients with polycystic ovarian syndrome who are undergoing in vitro fertilization because it may reduce the incidence of ovarian hyperstimulation syndrome. (I-A)2.Gonadotropin dosing should be carefully individualized, taking into account the patient’s age, body mass, antral follicle count, and previous response to gonadotropins. (II-3B)3.Cycle cancellation before administration of human chorionic gonadatropin is an effective strategy for the prevention of ovarian hyperstimulation syndrome, but the emotional and financial burden it imposes on patients should be considered before the cycle is cancelled. (III-C)4.Gonadotropin-releasing hormone (GnRH) antagonist stimulation protocols are recommended in patients at high risk for ovarian hyperstimulation syndrome (OHSS). The risk of severe OHSS in patients on GnRH antagonist protocols who have a very robust ovarian stimulation response can be reduced by using a GnRH agonist as a substitute for human chorionic gonadotropin to trigger final oocyte maturation. (I-B)5.A gonadotropin-releasing hormone (GnRH) antagonist protocol with a GnRH agonist trigger for final oocyte maturation is recommended for donor oocyte and fertility preservation cycles. (III-C)6.Albumin or other plasma expanders at the time of egg retrieval are not recommended for the prevention of ovarian hyperstimulation syndrome. (I-E)7.Elective single embryo transfer is recommended in patients at high risk for ovarian hyperstimulation syndrome. (III-C)8.Progesterone, rather than human chorionic gonadotropin, should be used for luteal phase support. (I-A)9.Outpatient culdocentesis should be considered for the prevention of disease progression in severe ovarian hyperstimulation syndrome. (II-2B)

Hormone exposure and venous thromboembolism in commercially insured women aged 50 to 64 years

BackgroundMenopausal hormone therapy (MHT) can elevate venous thromboembolism (VTE) risk, but less is known about formulations and routes of exposures. ObjectiveTo estimate hormone-associated VTE risk by route and formulation in exposed and unexposed women aged 50 to 64 years in the US. MethodsIn a nested case-control study of US commercially insured women aged 50 to 64 years (2007-2019), cases were defined as incident VTE diagnoses and matched to 10 controls by date of VTE and age, excluding prior VTE, inferior vena cava filter placement, or anticoagulants. Filled prescriptions in the prior year defined hormone exposures. International Classification of Diseases and Current Procedural Terminology codes identified risk factors and comorbidities. ResultsOdds ratios (ORs) were estimated with conditional logistic regression controlling for differences between cases (n = 20,359) and controls (n = 203,590) in comorbidities and VTE risk factors. For exposures within 60 days, oral MHT risk was almost twice as high as transdermal MHT (OR = 1.92; 95% CI, 1.43-2.60); transdermal MHT did not elevate risk compared with no exposure (unopposed OR = 0.70; 95% CI, 0.59-0.83; combined OR = 0.73; 95% CI, 0.56-0.96). Risk was highest for MHT combinations with ethinyl estradiol, followed by conjugated equine estrogen (CEE) (ethinyl estradiol-CEE: OR = 1.55; 95% CI, 1.07-2.25), and lowest for estradiol (CEE-estradiol: OR = 1.33; 95% CI, 1.02-1.72). Combined hormonal contraceptives elevated risk 5 times higher than no exposure (OR = 5.22; 95% CI, 4.67-5.84) and 3 times higher than oral MHT (OR = 3.65; 95% CI, 3.09-4.31). ConclusionThe risk of VTE is much lower with MHT than combined hormone contraceptives and varies by hormone formulation and route of exposure. Transdermal MHT did not elevate risk. Oral MHT combinations with estradiol were lower risk than other forms of estrogen. Oral combined hormone contraceptives had much higher risk than oral combined hormonal MHT.

Modification of Tubings for Peristaltic Pumping of Biopharmaceutics

Protein particle formation during peristaltic pumping of biopharmaceuticals is due to protein film formation on the inner tubing surface followed by rupture of the film by the roller movement. Protein adsorption can be prevented by addition of surfactants as well as by increasing the hydrophilicity of the inner surface. Attempts based on covalent surface coating were mechanically not stable against the stress of roller movement. We successfully incorporated surface segregating smart polymers based on a polydimethylsiloxane (PDMS) backbone and polyethylene glycol (PEG) side blocks in the tubing wall matrix. For this we applied an easy, reproducible and cost-effective process based on soaking of tubing in toluene containing the PDMS-PEG copolymer. With this tubing modification we could drastically reduce protein particle formation during peristaltic pumping of a monoclonal antibody and human growth hormone (HGH) formulation in silicone and thermoplastic elastomer-based tubing. The modification did not impact the tubing integrity during pumping while hydrophilicity was increased and protein adsorption was prevented. Free PDMS-PEG copolymer might have an additional stabilizing effect, but less than 50 ppm of the PDMS-PEG copolymer leached from the modified tubing during 1 h of pumping in the experimental setup. In summary, we present a new method for the modification of tubings which reduces protein adsorption and particle formation during any operation involving peristaltic pumping, e.g. transfer, filling, or tangential flow filtration.

The Role of Hormone Therapy in Female Aesthetic Rejuvenation.

Hormones are intricately involved in age-related aesthetic changes. Declining levels of several hormones in the postmenopausal period are associated with unwanted changes in appearance, including weight gain, fat redistribution, aged skin, and hair thinning. Hormone therapies may prevent or reverse these changes. In this article, we explore the role of estrogen, progesterone, testosterone, dehydroepiandrosterone, and melatonin in female aesthetics. Based on our current understanding of the literature, dermatologists may safely and efficaciously incorporate several hormone formulations in their repertoire of treatments for female aesthetic rejuvenation. J Drugs Dermatol. 2022;21(9):954-960. doi:10.36849/JDD.6232.

Use of thyroid hormone in hypothyroid patients and euthyroid subjects in Spain: A THESIS* questionnaire survey

BackgroundHypothyroidism is one of the leading conditions in endocrinology. Despite that fact, clinical indications for treatment still vary among Spanish specialists. AimsTo identify attitudes of Spanish specialists relating to the use of levothyroxine (LT4) and the management of hypothyroidism. MethodsThe members of the Sociedad Española de Endocrinología y Nutrición (Spanish Society of Endocrinology and Nutrition) were invited to participate in a web-based survey. The survey, initially in English, was modified to reflect in accordance with the availability of thyroid hormone formulations in Spain. ResultsA total of 505 of 1956 (25.8%) members (66% female) completed the survey; 97.4% declared that LT4 is the first-line therapy for hypothyroidism. The indications for LT4 therapy in euthyroidism were infertility in thyroid antibody-positive women (48.5%) and simple goitre (21.2%). However, 44.2% of specialists reported that there was no indication for LT4 therapy in such patients. Only a minority of respondents (2.6%) considered combining LT4 with liothyronine as the treatment of choice from inception, whereas 49% stated that it should never be used. ConclusionsThe standard of treatment of hypothyroidism in Spain is almost exclusively with LT4 tablets. Availability of other formulations of LT4 or combination therapy for hypothyroidism management remains to be explored, especially in patients with persistent symptoms. Notably, non-evidence-based use of LT4 is widely practiced in Spain for euthyroid women with autoimmune thyroiditis and fertility issues.

Comparing estrogen-based hormonal contraceptives and hormone therapy on bone mineral density in women with premature ovarian insufficiency: a systematic review.

Premature ovarian insufficiency (POI) is a condition associated with estrogen deficiency which leads to decreased bone mineral density and an increased risk of osteoporosis and fractures. Estrogen-based hormone therapy is an integral component of treatment; however, to date the ideal hormone formulation for optimizing bone health has not been established. To assess the effects of estrogen-based oral contraceptives (OCP) versus hormone therapy (HT) on bone mineral density (BMD) in women with POI. A systematic review of Ovid MEDLINE, EMBASE, Cochrane Library, and Web of Science databases was conducted from conception until December 2020. Randomized controlled trials (RCTs) and observational studies that met inclusion criteria were included in the analysis. Risk of bias was assessed with the Newcastle-Ottawa Quality Assessment Scale for cohort studies and the Cochrane Risk of Bias for RCTs. The study protocol was registered with the International Prospective Register of Systematic Reviews and adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Our search yielded 1,227 studies; 3 RCTs and 2 observational cohort studies met inclusion criteria and were included in our study. The largest subpopulation was Turner Syndrome (n = 625), followed by idiopathic POI (n = 146). Of the four studies that assessed changes in BMD, two studies reported a significant increase in lumbar spine BMD with HT compared with OCP (+0.050 g/cm2, P < 0.025; +0.019 g/cm2, P < 0.01), one study found similar improvement in lumbar spine BMD across treatments (HT -0.003 g/cm2, P = 0.824), and one study did not directly compare treatments. Effects on bone turnover markers were inconsistent across three studies that evaluated this outcome. This is the first systematic review to include studies that directly compared OCP and HT on bone outcomes in POI. While two studies reported increased lumbar spine BMD with HT, this result was not consistently found across studies. There were important differences in POI etiology, treatment regimens and formulations, and risk of bias was high in many of the studies. These results indicate future, larger-scale trials are needed to further understand the optimal hormone therapy for bone density in POI.

Effects of plant growth regulators and growing media on propagation and field establishment of Stevia rebaudiana: a medicinal plant of commerce

BackgroundStevia rebaudiana is an economically important medicinal plant that has generated interest among the growers and pharmacologists in terms of its industrial or pharmaceutical value. For the mass production of the seedlings, easy and convenient techniques are lacking while, micro propagation was reported promising but still out of reach at farm level. The unavailability of quality planting materials due to non-viable seeds is restricting its mass commercial scale cultivation. The present study was therefore attempted to standardize the plant growth regulators and growing media to standardize the vegetative propagation protocol through cuttings for its mass multiplication in Terai region of West Bengal, India.MethodsGrowing media (soil, FYM, saw dust and sand) as sole and in combination and growth hormones (IAA, IBA and NAA in different concentration and a commercial formulation i.e. Totoroot© with different exposure time) were compared with control (i.e. sole soil and no hormone treatment, respectively) to standardize the nursery protocol of Stevia.ResultsSand used as sole was found the best growing media for survival and growth of cuttings while, cuttings treated with commercial growth hormone formulation for 5 mins was best. Cuttings treated with commercial growth hormone formulation performed significantly better in the field with respect to survival, growth and production of leaves.ConclusionThe study recommends the use of sole sand media and commercial growth hormone formulation with 5 mins exposure time for mass nursery production of Stevia cuttings in Terai zone of West Bengal due to their better performance both in the nursery and after transplanting in the field.

Oral Bioavailability Enhancement of Melanin Concentrating Hormone, Development and In Vitro Pharmaceutical Assessment of Novel Delivery Systems.

The rapid progress in biotechnology over the past few decades has accelerated the large-scale production of therapeutic peptides and proteins, making them available in medical practice. However, injections are the most common method of administration; these procedures might lead to inconvenience. Non-invasive medications, such as oral administration of bio-compounds, can reduce or eliminate pain and increase safety. The aim of this project was to develop and characterize novel melanin concentrating hormone (MCH) formulations for oral administration. As a drug delivery system, penetration enhancer combined alginate beads were formulated and characterized. The combination of alginate carriers with amphiphilic surfactants has not been described yet. Due to biosafety having high priority in the case of novel pharmaceutical formulations, the biocompatibility of selected auxiliary materials and their combinations was evaluated using different in vitro methods. Excipients were selected according to the performed toxicity measurements. Besides the cell viability tests, physical properties and complex bioavailability assessments were performed as well. Our results suggest that alginate beads are able to protect melanin concentrating hormones. It has been also demonstrated that penetration enhancer combined alginate beads might play a key role in bioavailability improvement. These formulations were found to be promising tools for oral peptide delivery. Applied excipients and the performed delivery systems are safe and highly tolerable; thus, they can improve patients’ experience and promote adherence.

Use of thyroid hormone in hypothyroid patients and euthyroid subjects in Spain: A THESIS* questionnaire survey

BackgroundHypothyroidism is one of the leading conditions in endocrinology. Despite that fact, clinical indications for treatment still vary among Spanish specialists. AimsTo identify attitudes of Spanish specialists relating to the use of levothyroxine (LT4) and the management of hypothyroidism. MethodsThe members of the Sociedad Española de Endocrinología y Nutrición (Spanish Society of Endocrinology and Nutrition) were invited to participate in a web-based survey. The survey, initially in English, was modified to reflect in accordance with the availability of thyroid hormone formulations in Spain. ResultsA total of 505 of 1956 (25.8%) members (66% female) completed the survey; 97.4% declared that LT4 is the first-line therapy for hypothyroidism. The indications for LT4 therapy in euthyroidism were infertility in thyroid antibody-positive women (48.5%) and simple goitre (21.2%). However, 44.2% of specialists reported that there was no indication for LT4 therapy in such patients. Only a minority of respondents (2.6%) considered combining LT4 with liothyronine as the treatment of choice from inception, whereas 49% stated that it should never be used. ConclusionsThe standard of treatment of hypothyroidism in Spain is almost exclusively with LT4 tablets. Availability of other formulations of LT4 or combination therapy for hypothyroidism management remains to be explored, especially in patients with persistent symptoms. Notably, non-evidence-based use of LT4 is widely practiced in Spain for euthyroid women with autoimmune thyroiditis and fertility issues.

Should Exogenous Estrogens Be Stopped for Surgery in Transgender Women?

Should Exogenous Estrogens Be Stopped for Surgery in Transgender Women?

Clinically Used Hormone Formulations Differentially Impact Memory, Anxiety-Like, and Depressive-Like Behaviors in a Rat Model of Transitional Menopause.

A variety of U.S. Food and Drug Administration-approved hormone therapy options are currently used to successfully alleviate unwanted symptoms associated with the changing endogenous hormonal milieu that occurs in midlife with menopause. Depending on the primary indication for treatment, different hormone therapy formulations are utilized, including estrogen-only, progestogen-only, or combined estrogen plus progestogen options. There is little known about how these formulations, or their unique pharmacodynamics, impact neurobiological processes. Seemingly disparate pre-clinical and clinical findings regarding the cognitive effects of hormone therapies, such as the negative effects associated with conjugated equine estrogens and medroxyprogesterone acetate vs. naturally circulating 17β-estradiol (E2) and progesterone, signal a critical need to further investigate the neuro-cognitive impact of hormone therapy formulations. Here, utilizing a rat model of transitional menopause, we administered either E2, progesterone, levonorgestrel, or combinations of E2 with progesterone or with levonorgestrel daily to follicle-depleted, middle-aged rats. A battery of assessments, including spatial memory, anxiety-like behaviors, and depressive-like behaviors, as well as endocrine status and ovarian follicle complement, were evaluated. Results indicate divergent outcomes for memory, anxiety, and depression, as well as unique physiological profiles, that were dependent upon the hormone regimen administered. Overall, the combination hormone treatments had the most consistently favorable profile for the domains evaluated in rats that had undergone experimentally induced transitional menopause and remained ovary-intact. The collective results underscore the importance of investigating variations in hormone therapy formulation as well as the menopause background upon which these formulations are delivered.

Population Pharmacokinetics and Pharmacodynamics of Once-Daily Growth Hormone Norditropin® in Children and Adults.

Background and ObjectiveOnce-daily injectable recombinant human growth hormone (GH) formulations (e.g. Norditropin®; Novo Nordisk A/S) are used to treat GH deficiency in children and adults, with much of the therapeutic effect mediated via the insulin-like growth factor-I (IGF-I) response. Despite a long history of use, there are few data on the pharmacokinetics and pharmacodynamics (serum IGF-I response) of this therapy, or of potential differences in the relationship of GH pharmacokinetic/pharmacodynamic (PK/PD) effects between children and adults. This study aimed to characterise the GH pharmacokinetics and IGF-I profile following daily subcutaneous GH in adults and children with GH deficiency.MethodsA model was developed based on a population PK/PD modelling meta-analysis of data from three phase I clinical trials (two using Norditropin® as a comparator with somapacitan, and one as a comparator with a pegylated GH product). Sequential model building was performed, first developing a model that could describe GH pharmacokinetics. A PD model of IGF-I data was then developed using PK and PD data, and where all PK parameters were kept fixed to those estimated in the PK model.ResultsThe model developed accurately describes and predicts GH pharmacokinetics and IGF-I response. Body weight was shown to have an important inversely correlated influence on GH exposure (and IGF-I standard deviation score), and this largely explained differences between adults and children.ConclusionsThe pharmacokinetics/pharmacodynamics developed here can inform expectations about the PD effects of different doses of GH in patients with GH deficiency of different body weights, regardless of their age.Clinical Trial RegistrationPooled modelling analysis of data from ClinicalTrials.gov identifiers NCT01973244, NCT00936403 and NCT01706783.Dates of registrationNCT01973244: 22 October, 2013; NCT00936403: 9 July, 2009; NCT01706783: 11 October, 2012.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40262-021-01011-3.

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.

Menopausal Hormone Therapy and Cardiovascular Disease: The Role of Formulation, Dose, and Route of Delivery.

This mini-review provides an overview of menopausal hormone therapy (HT) and cardiovascular disease (CVD) risk, with a focus on the role of hormone formulation, dose, and route of delivery. This summary is based on authors' knowledge in the field of menopausal HT and supplemented by a PubMed search using the terms "menopause hormone therapy," "transdermal," "estradiol," "conjugated estrogens," "bioidentical," "cardiovascular disease," "lipoproteins," "glucose," "progestogens," "low dose." Available evidence indicates that oral unopposed estrogens have a favorable effect on lipoprotein levels, glycemia, insulin, and CVD risk; however, the addition of progestogens blunts the lipid-related effects. The progestogen with the smallest attenuating effect is micronized progesterone. Transdermal estrogens have less effect on coagulation, inflammation, and lipids than oral estrogens and observational studies suggest they pose a lower risk of venous thromboembolism and stroke than oral estrogens. Clinical effects of hormones were not consistently dose dependent. Although HT continues to have an important role in menopause management, it is not recommended for primary or secondary CVD prevention. Different formulations, doses, and routes of delivery of HT have different effects on cardiometabolic markers and risks of clinical CVD events. However, long-term trials evaluating clinical outcomes with transdermal and other alternate HT regimens are limited.

Which U.S. States’ Medicaid Programs Provide Coverage for Gender-Affirming Hormone Therapy and Gender-Affirming Genital Surgery for Transgender Patients?: A State-by-State Review, and a Study Detailing the Patient Experience to Confirm Coverage of Services

BackgroundTo date, a comprehensive state-by-state assessment of transgender transition-related health care coverage for gender-affirming hormone therapy (GAHT) and genital gender-affirming surgery (GAS) has not been reported. AimsThe aims of this study were 1) to verify which U.S. states’ Medicaid systems do/do not cover GAHT and GAS; 2) to assess the ease/difficulty for patients to determine whether GAHT and GAS are Medicaid-covered benefits; and 3) to understand possible state-related predictors of Medicaid coverage for gender-affirming care. MethodsWe reviewed the official Medicaid Handbook and website for all 51 states (+D.C.) and 5 territories to confirm whether GAHT and GAS are covered benefits. When indeterminate, we called the Medicaid office in each state, and for many, Medicaid managed care organizations (MCOs), and individual in-state providers, to confirm coverage. We recorded our experiences, number of, and duration of phone calls to confirm coverage. OutcomesThe main outcome was a definitive answer from the state/territory's Medicaid program or MCOs regarding whether GAHT and GAS are/are not covered benefits. Secondary outcome measures included responses we received and the total number/duration of phone calls necessary to confirm coverage. ResultsOnly 12 of 51 states and 0 of 5 territories featured their policy regarding coverage for GAHT in their Medicaid Handbook/webpages. We confirmed that 34 of 51 state Medicaid programs do cover GAHT, whereas 9 of 51 states' and 2 of 5 territories’ do not. We could not confirm coverage of GAHT in 8 of 51 states and 3 of 5 territories.Only 26 of 51 states and 0 of 5 territories featured their policy regarding coverage for GAS in their Medicaid Handbook/webpages. We confirmed that 25 of 51 state Medicaid programs do cover GAS, whereas 22 of 51 states' and 3 of 5 territories’ do not. We could not confirm coverage of GAS in 4 of 51 states and 2 of 5 territories. Up to 12 calls, lasting up to 125 minutes, were required to confirm coverage for GAHT/GAS. Clinical ImplicationsOur findings indicate that important health care access barriers/disparities exist today and warrant improvement. Strengths & LimitationsTo our knowledge, this is the most comprehensive assessment of transgender transition-related health care coverage. Limitations include possible bias, as it could be that we were more persistent than actual patients would be to determine service coverage, and a lack of specificity regarding which specific hormone formulations or procedures are/are not covered. ConclusionOur findings show that only 34 of 51 (67%) states’ Medicaid programs include GAHT and 25 of 51 (49%) include GAS as covered benefits. Our experience suggests that the process to confirm coverage can be especially time-consuming and frustrating for patients.Zaliznyak M, Jung EE, Bresee C, et al. Which U.S. States’ Medicaid Programs Provide Coverage for Gender-Affirming Hormone Therapy and Genital Gender-Affirming Surgery for Transgender Patients?: A State-by-State Review, and a Study Detailing the Patient Experience to Confirm Coverage of Service. J Sex Med 2021;18:410–422.