Bioidentical Hormone Prescribing Guide
Introduction
The use of bioidentical hormones in clinical practice has grown significantly as an evidence-informed approach to managing hormonal imbalances and supporting overall health. This guidebook is designed to serve as a trusted resource for healthcare providers, offering clear, concise, and practical recommendations for prescribing bioidentical hormones. Drawing on the latest research and clinical expertise, it provides actionable insights into patient assessment, hormone selection, dosing strategies, and ongoing monitoring. As personalized medicine becomes increasingly central to patient care, bioidentical hormones offer a tailored solution to addressing complex hormonal health concerns. By understanding the principles outlined in this guide, providers can optimize treatment outcomes while maintaining a focus on patient safety and satisfaction. This resource is intended to empower providers with the knowledge needed to collaborate effectively and deliver individualized hormonal therapies within an integrative practice setting.
A Living Resource: Welcoming Your Input
This guide is a dynamic resource, reflecting the evolving landscape of bioidentical hormone therapy and integrative healthcare practices. We are committed to maintaining its relevance and accuracy by incorporating the latest evidence and feedback from experienced providers like you. Your insights and recommendations are invaluable in ensuring this guide meets the needs of practitioners and supports the highest standard of patient care. If you have suggestions or feedback on any aspect of this guide, we encourage you to share them with us. Please email your input to info@onin.ca. Together, we can continue to refine and enhance this resource for the benefit of providers and patients alike.
Summary of Evidence for BHRT in Women
Hormone Replacement Therapy (HRT) has been studied extensively concerning its impact on all-cause mortality, cardiovascular mortality, and cancer incidence. The evidence suggests nuanced effects that vary by timing, formulation, and patient subgroups. Recent meta-analyses offer clarity on its relative safety and risks.
Key Findings
All-Cause Mortality:
A 2022 meta-analysis indicated a reduction in all-cause mortality for women initiating HRT early in menopause, particularly with estradiol-based therapies. This suggests a "timing hypothesis" where starting HRT closer to menopause onset may confer survival benefits. (Hodis & Mack, 2022)
Another systematic review concluded that mortality benefits are most pronounced in younger postmenopausal women, emphasizing age-specific outcomes. (Salpeter et al., 2009)
Cardiovascular Mortality
Meta-analyses show mixed results. Estradiol-based HRT might reduce cardiovascular mortality in younger women but increases risks in older women. The mode of administration (oral vs. transdermal) also influences cardiovascular outcomes, with transdermal routes being safer. (Mikkola et al., 2015)
Cardiovascular risk is associated with progestins, particularly medroxyprogesterone acetate, suggesting the need for careful formulation selection.
Cancer Risks
Breast cancer risk increases slightly with long-term use of combined estrogen-progestin therapy. However, estrogen-alone regimens in women with hysterectomy may lower breast cancer risk. (Benkhadraet al., 2015)
For endometrial cancer, combined HRT reduces risks compared to unopposed estrogen. HRT's effects on ovarian cancer remain inconclusive but suggest modest increases in risk with long-term use.
Subgroups and Special Considerations
Women with prior breast cancer require tailored approaches due to conflicting evidence on HRT's safety. (Mudhuneet al., 2019)
Timing and type of HRT significantly impact cardiovascular outcomes, supporting early initiation after menopause.
Meta-Analyses
1) Menopausal Hormone Therapy and Mortality (Benkhadra et al., 2015)
2) Estradiol-Based Postmenopausal HRT (Mikkola et al., 2015)
3) Safety in Breast Cancer Survivors (Mudhune et al., 2019)
4) Bayesian Meta-Analysis of HRT (Salpeter et al., 2009)
5) Impact of Timing on Mortality (Nudy et al., 2019)
Reccommendations
Individualization: The decision to initiate HRT should consider age, comorbidities, timing relative to menopause, and specific formulations.
Monitoring: Ongoing surveillance for cardiovascular and cancer risks is critical during HRT
Summary of Evidence: Safety of Testosterone Replacement Therapy (TRT) in Men
Overview
Testosterone replacement therapy (TRT) is widely used for managing hypogonadism in men, addressing symptoms like low libido, fatigue, and reduced muscle mass. However, concerns about cardiovascular safety, cancer risks, and other adverse effects persist. Meta-analyses and systematic reviews provide critical insights into TRT's benefits and risks.
Key Findings
Cardiovascular Safety
Neutral to Slight Risk Increase: Some meta-analyses, such as those by Ponce et al. (2018), indicate no significant increase in major adverse cardiovascular events (MACE) with TRT. However, subgroups, particularly those with preexisting cardiovascular disease, may face increased risks. (Ponce et al., 2018)
Venous Thromboembolism (VTE): Another meta-analysis by Ayele et al. (2021) highlights a modest association between TRT and VTE, emphasizing the need for careful patient selection. (Ayele et al., 2021)
Cancer Risks
Prostate Cancer: TRT does not significantly increase prostate cancer risk, as demonstrated in a meta-analysis by Cui et al. (2014). Men with a history of prostate cancer need individualized evaluation before TRT. (Cui et al., 2014)
Oncology in Survivors: TRT is cautiously applied in prostate cancer survivors, with studies showing no significant adverse outcomes in men treated after curative therapy. (Parizi et al., 2019)
Mortality and General Safety
All-Cause Mortality: TRT may reduce all-cause mortality in hypogonadal men compared to untreated individuals, as reported by Hackett (2016). This suggests benefits from symptom management and metabolic improvements. (Hackett, 2016)
Adverse Effects: A systematic review by Murad et al. (2010) lists erythrocytosis as the most common adverse effect of TRT, along with a slightly increased risk of cardiovascular events in certain populations. (Murad et al., 2010)
Meta-Analyses
1) Cardiovascular Safety and MACE Risk (Ponce et al., 2018)
2) Venous Thromboembolism Risk (Ayele et al., 2021)
3) Prostate Cancer Risks (Cui et al., 2014)
4) Oncology in Prostate Cancer Survivors (Parizi et al., 2019)
5) All-Cause Mortality (Hackett, 2016)
6) General Safety and Erythrocytosis (Murad et al., 2010)
7) Bone Health and Fracture Risk (Buratto et al., 2023)
Recommendations
Individualized Assessment: Patients should undergo comprehensive evaluations for cardiovascular and cancer risks before initiating TRT.
Monitoring: Regular hematological, prostate, and cardiovascular monitoring is crucial.
Patient Intake and Assessment
A comprehensive and integrative approach to patient intake and assessment is foundational to effective hormonal health management. This process goes beyond traditional clinical evaluations to consider the intricate interplay of diet and lifestyle, mental and emotional well-being, environmental exposures, and genomic and epigenomic factors that influence hormonal balance.
Lifestyle: Key elements such as diet, physical activity, sleep quality, and stress management play a pivotal role in hormonal regulation. Detailed inquiries in to daily routines, nutritional habits, and activity levels provide essential insights into potential lifestyle modifications that may enhance therapeutic outcomes. A list of clinically validated diet and lifestyle assessment tools that can use as part of your patient intake and ongoing assessment can be found in Appendix A.
Mental and Emotional Well-Being: Psychological health is deeply interconnected with hormonal function. Factors such as chronic stress, emotional trauma, and mood disorder scan significantly disrupt hormonal homeostasis. Assessing mental and emotional resilience enables the development of tailored interventions to support both psychological and physiological health. A list of clinically validated mental health assessment tools that can use as part of your patient intake and ongoing assessment can be found in Appendix B.
Environmental Impacts: Environmental toxins, endocrine-disrupting chemicals, and occupational exposures can have profound effects on hormonal systems. A thorough review of the patient’s environment, including potential sources of toxic exposure, helps identify contributors to hormonal dysregulation and opportunities for mitigation.A sample Enivronmental Exposure Questionnaire that can be used as a template for you patients can be found in Appendix C.
Genomic and Epigenomic Influences: Genetic predispositions and epigenetic modifications shape individual hormonal responses and susceptibilities. Understanding family health history and, when appropriate, utilizing advanced genomic testing can provide insights into personalized care strategies that address unique genetic and epigenetic profiles. This integrative approach ensures that the patient’s hormonal health is addressed holistically, laying the groundwork for sustainable and individualized therapeutic interventions. By exploring these multifaceted dimensions, practitioners can more effectively identify root causes of imbalances and empower patients to achieve optimal health and vitality.
Laboratory Assessments
The following labs are recommended (additional assessment beyond this is possible depending on the patient presentation) for initial patient assessment and to be repeated as needed for ongoing treatment monitoring:
Thyroid
Serum TSH, T4, T3, and Thyroid antibodies
Adrenal
Serum am/pm cortisol, DHEAS, Free and total testosterone
Salivary cortisol 2–4-point measurements
Reproductive Hormones
Female
Serum LH, FSH, Estradiol, Estriol, Estrone, Progesteroneo
DUTCH testing
Male
Serum LH, FSH, testosterone (free and total)
PSA in case of testosterone replacement therapy
Metabolic Assessment
CBC with differential
Fasting blood sugar, insulin, HbA1c
Serum lipids
Inflammatory Markers
ESR
CRP
Imaging Assessment
For patients receiving estrogen and/or progesterone therapy consider pre-treatment, and ongoing monitoring (as needed) using pelvic/transvaginal ultrasound, mammogram/breast ultrasound.
Other Assessment Tools
A comprehensive patient assessment can also include a number of clinically validated assessment tools for diet, lifestyle, and mental health. These tools provide valuable insights into patient health status and help guide personalized treatment plans. Click below to access an updated list with links to these tools.
Informed Consent Discussion Script for Providers
Informed Consent Script and Documentation - Safety of HRT in Women
Benefits of HRT
"HRT is commonly used to treat menopausal symptoms, such as hot flashes, night sweats, mood changes, and vaginal dryness. It can also help with bone health, reducing the risk of osteoporosis-related fractures, especially in women who are at higher risk. For many women, HRT significantly improves quality of life during menopause and in pre/peri menopausal situations of hormonal imbalance."
Risks of HRT
"As with any treatment, there are potential risks with HRT. These risks depend on factors like your age, how close you are to menopause, your overall health, and the specific type of HRT. While the evidence is less robust, BHRT is likely safer than conventional HRT therapy. Let me break this down into key areas:
All-Cause Mortality: Studies suggest that starting HRT close to menopause (within 10 years) may reduce overall mortality, especially for younger, healthy women. However, this benefit may not apply if HRT is started later in life.
Cardiovascular Risks: HRT started early in menopause has been associated with reduced cardiovascular risks in some women. However, starting HRT later in life (more than 10 years after menopause) or in those with preexisting cardiovascular disease may increase the risk of heart disease or stroke. The method of delivery also matters; transdermal options pose lower risks compared to oral formulations.
Cancer Risks: Combined HRT (estrogen and synthetic progestins) may slightly increase the risk of breast cancer with long-term use, especially beyond five years. However, the risk decreases once HRT is stopped. Bioidentical progesterone therapy may carry lower, or no risk of breast cancer compared to synthetic progestins when used in combination with estrogen for hormone replacement therapy (HRT). Studies suggest that bioidentical progesterone does not significantly increase breast cancer risk in short-term use, particularly when started around menopause. However, the long-term risk remains uncertain, and close monitoring is recommended for all women undergoing HRT. Estrogen-only HRT in women without a uterus appears to have a lower risk of breast cancer. HRT does not significantly increase the risk of endometrial cancer if progesterone is used alongside estrogen.
Blood Clots: There is a small increase in the risk of blood clots, such as deep vein thrombosis or pulmonary embolism, particularly with oral conventional HRT. This risk is lower with transdermal options like patches, creams or gels."
Alternatives to HRT
"If you are concerned about these risks, there are non-hormonal treatments and lifestyle adjustments that can help manage menopausal symptoms and reduce osteoporosis risk."
Personalizing the Decision
"The safety and benefits of HRT depend on your personal health profile. If you decide to proceed, we’ll choose the type and dose of HRT that fits your needs best, and I’ll closely monitor your progress and health over time. If you decide against HRT, we can explore other options that align with your preferences and health goals."
Informed Consent
"To ensure you are comfortable with the decision, do you have any questions or concerns about what I’ve explained so far? Let’s go through those together so you feel fully informed."
Emphasizing Follow-Up
"Remember, the decision to start or stop HRT is not set in stone. We can reassess at any time and adjust based on how you feel and any changes in your health. Regular check-ups will allow us to monitor any risks and ensure you are benefiting from the therapy."
Click here to download an Informed Consent template to add to your EMR (BHRT Safety in Women)Informed Consent Script and Documentation - Safety of TRT in Men
Benefits of TRT
"TRT is used to treat low testosterone levels, which can cause symptoms like low energy, reduced libido, difficulty building muscle, mood changes, and bone loss. In men with clinically confirmed low testosterone, TRT can improve these symptoms, enhance quality of life, and support long-term bone and muscle health."
"If you’re hesitant about TRT, there are lifestyle changes and other treatments that may help improve your symptoms. Weight management, exercise, and addressing underlying health conditions like sleep apnea can naturally improve testosterone levels. We can explore these options further if needed."
Risks of HRT
"As with any therapy, TRT has potential risks that depend on your overall health, age, and medical history. Here’s what you need to know:
Cardiovascular Risks:
Studies on TRT and cardiovascular risks have mixed results. For men with no history of cardiovascular disease, TRT appears to have a neutral to modestly beneficial effect. However, in men with preexisting cardiovascular conditions, there may be a small increased risk of heart attack, stroke, or blood clots, especially shortly after starting therapy. We’ll assess your cardiovascular risk carefully before starting TRT.
Cancer Risks:
TRT does not appear to increase the risk of developing prostate cancer. However, in men with existing prostate cancer or high PSA levels, TRT requires close monitoring as it may stimulate cancer growth. There is no significant evidence linking TRT to an increased risk of other cancers.
Blood Clots:
TRT may slightly increase the risk of deep vein thrombosis or pulmonary embolism. This risk is low but will be evaluated based on your personal and family history.
Other Side Effects:
TRT can cause increased red blood cell production (erythrocytosis), which may require monitoring and adjustments. Other potential side effects include acne, fluid retention, and fertility changes."
Alternatives to HRT
Personalizing the Decision
"The safety and benefits of HRT depend on your personal health profile. If you decide to proceed, we’ll choose the type and dose of HRT that fits your needs best, and I’ll closely monitor your progress and health over time. If you decide against HRT, we can explore other options that align with your preferences and health goals."
Informed Consent
"Do you have any questions or concerns about what I’ve explained so far? It’s important to me that you feel fully informed and comfortable with your decision. We can take as much time as you need to discuss this."
Monitoring and Follow-Up
"If you choose to start TRT, we’ll begin with a comprehensive evaluation, including lab tests and a discussion of your health history. During treatment, I’ll monitor your symptoms, testosterone levels, and potential side effects with regular follow-ups. This ensures we adjust the therapy as needed to keep it safe and effective. Remember, starting TRT is not a permanent decision. If at any time you feel it’s not benefiting you or you have concerns, we can stop or adjust the treatment. My priority is your health and well-being."
Click here to download an Informed Consent template to add to your EMR (TRT in Men)HRT Prescribing
Progesterone
Common Indications:
Menopausal Symptoms
Vasomotor Symptoms: Hot flashes and night sweats.
Sleep Disturbances: Insomnia or disrupted sleep due to hormonal changes.
Urogenital Symptoms: Vaginal dryness, atrophy, and discomfort during intercourse.
Mood Changes: Depression, anxiety, and mood swings linked to hormonal fluctuations.
Prevention of endometrial hyperplasia in women receiving estrogen therapy
Menstrual Irregularities
Premenstrual Syndrome and Premenstrual Dysphoric Disorder
Endometriosis
Abnormal Uterine Bleeding
Polycystic Ovary Syndrome
OsteoporosisTreatment/Prevention
Premature Ovarian Failure/Insufficiency
Contraindications
History of breast cancer orestrogen-dependent cancers.
Active thromboembolic disordersor stroke.
Severe liver disease.
Unexplained vaginal bleeding.
Dosing Guidance
Frequency
Post-menopausal – Monday to Saturday; break on Sunday to avoid downregulation of receptors
Pre-menopausal – day 15-28
Dosing Levels
Topical
Pre-menopausal – 5-30 mg daily at bedtime day 15-28
Post-menopausal – 10-30 mg daily at bedtime Monday to Saturday; escalation at 5 mg increments
For patient application instructions, see resource.
Oral
Pre-menopausal – 50-150 mg daily at bedtime day 15-28 (or until menses begins if it occurs before day 28)
Post-menopausal – 75-300 mg daily at bedtime Monday to Saturday; escalation at 25 mg increments
Signs of Over Supplementation:
Slow to wake up or groggy
Breast tenderness
Cystic acne
Low mood
Swelling in hands and feet
Sluggish bowels
Hot flashes
Insulin resistance and weight gain
Tip: If your EMR supports templates or phrases, you can copy the typical dosing amounts into a phrase and then modify as needed. This can also include patient instructions and safety information.
Estradiol
Common Indications:
Menopausal Symptoms
Vasomotor Symptoms: Hot flashes and night sweats.
Sleep Disturbances: Insomnia or disrupted sleep due to hormonal changes.
Urogenital Symptoms: Vaginal dryness, atrophy, and discomfort during intercourse.
Mood Changes: Depression, anxiety, and mood swings linked to hormonal fluctuations.
Premenstrual Syndrome and Premenstrual Dysphoric Disorder
OsteoporosisTreatment/Prevention
Premature Ovarian Failure/Insufficiency
Hypoestrogenism
Contraindications
Active or history of breast cancer or estrogen-dependent tumors
Uncontrolled hypertension or thromboembolic disorders
Undiagnosed abnormal uterine bleeding
General Guidance
For systemic effects Biest (estradiol and estriol) is used generally either (20:80 or 50:50)
Given daily day 1-25 to menstruating women
Given daily Monday to Saturday in post-menopausal women
Must be balanced with progesterone to prevent endometrial hyperplasia
Consider pre-assess to rule out breast lesion (mammogram or ultrasound) and/or existing endometrial
Dosing Guidance
Topical (only to avoid VTE and CVD risk)Dosing:
Pre-menopausal – Biest (80:20)0.1-0.25 daily, days 1-25; Escalation 0.05 mg increments
Post-menopausal – Biest (80:20)0.5-1.75 daily or twice daily Monday - Saturday; Escalation 0.05 mg increments
Estriol (for vaginal atrophy)
Dosing:
0.25-0.5 mg daily at bedtimefor 2 weeks, then twice weekly for 2 weeks then once per week for 2 months,then as needed
Estriol can be transferred tosexual partner so apply after intercourse or wait until the next morning (8+hours) before engaging in intercourse
For patient application instructions, see resource.
Signs of Over Supplementation:·
Irritability/weepiness
Acne
Breast tenderness
Swelling
Midcycle spotting or post-menopausal bleeding
Insulin resistance and weight gain
Testosterone Therapy in Women
Common Indications:
Hypoactive Sexual Desire Disorder
Menopausal Related Symptoms:
Fatigue
Mood Changes
Sarcopenia
Osteopenia/Osteoporosis
Declining Cognitive Function
Contraindications
Known or suspected androgen-dependent tumors.
History of severe acne or hirsutism
Pregnancy or breastfeeding
Dosing Guidance
Topical
0.5-1.25 mg per day transdermal Monday to Saturday; Escalation at 0.25mg increments
Sign of Oversupplementation
Angry/Aggressive
Acne/Oily Skin
Clitomegaly
Hirsutism
Deepening of the voice
Testosterone Therapy in Men
Common Indications:
Primary or secondary hypogonadism
Symptomatic Low Testosterone including:
Fatigue and Low Energy Levels
Loss of Libido and Erectile Dysfunction
Mood Disorders including depression or irritability linked to hormonal imbalances.
Cognitive Changes including difficulty concentrating or memory impairment
Sarcopenia in aging
Osteoporosis/Osteopenia
Contraindications
Prostate or breast cancer.
Severe benign prostatic hyperplasia (BPH) with obstructive symptoms
Uncontrolled heart failure or thromboembolic disorders
Polycythemia
Liver Disease
Elevated PSA
Severe sleep apnea
Male infertility
Dosing Guidance
Topical
40-120 mg transdermal daily Monday to Saturday; Escalation at 40 mg increments
Injection
TestosteroneEnanthate/Cypionate (Long-Acting)
Typical dose: 50–400 mg IM every 2–4 weeks.
Most common regimen: 100–200 mg IM every 1–2 weeks.
Adjust based on clinical response and serum testosterone levels, aiming for a mid-normal range (300–1,000 ng/dL)
Testosterone Undecanoate (Very Long-Acting)
Initial dose: 750 mg IM on day 0, followed by 750 mg after 4 weeks, then every 10 weeks thereafter.
Requires monitoring for side effects, especially pulmonary oil microembolism reactions.
Sign of Oversupplementation
Angry/Aggressive
Acne/Oily Skin
Excessive Hair Growth
Deepening of the voice
Dehydroepiandrosterone (DHEA)
General
Remember this hormone has downstream effects in the testosterone and estrogen pathways. 7 Keto-DHEA is not metabolized into reproductive hormones like testosterone and estradiol. It is often used for weight loss and thermogenesis and is dosed in the same manner as DHEA.
Common Indications:
Dyspareunia
Menopausal Symptoms: Vasomotor symptoms; Mood Changes
Adrenal Insufficiency
Systemic Lupus Erythematosus
Hypoactive Sexual Desire Disorder
Osteoporosis/Osteopenia
Cognitive Decline
Chronic Fatigue (Myalgic Encephalitis) and Fibromyalgia Syndrome
Contraindications
Hormone dependent Cancers: Breast, prostate and other estrogen/androgen sensitive cancers
Undiagnosed vaginal bleeding
Pregnancy
Breastfeeding
Active Liver Disease
Uncontrolled Cardiovascular Disease (caution)
Dosing Guidance
Forms
Topical dosing strategies are the same as sublingual…choice is personal preference and based on absorption with oral dosing vs sublingual
Women
4-10 mg in the morning Monday to Saturday; increase in increments of 2 mg
Men
10-20 mg in the morning Monday to Saturday; increase in increments of 5 mg
Sign of Oversupplementation
Same as Testosterone:
Angry/Aggressive
Acne/Oily Skin
Excessive Hair Growth
Deepening of the voice
Hydrocortisone
Common Indications:
Adrenal Insufficiency (Primary or Secondary): Replacement therapy for cortisol deficiency.
Contraindications
Active or latent tuberculosis.
Viral infections (e.g., herpes simplex, varicella)
Gastrointestinal disorders (e.g., diverticulitis, peptic ulcers, perforation risks)
Diabetes mellitus (requires careful monitoring)
Osteoporosis or severe bone density loss
Glaucoma and cataracts
Psychiatric disorders, such as severe mood instability or psychosis.
Dosing Guidance
5–30 mg/day in divided doses (20 mg morning, 10 mg afternoon)
Side Effects
Common Side Effects:
Fluid retention, weight gain
Increased appetite
Mood changes (e.g. irritability, anxiety)
Hyperglycemia
Serious Side Effects (unlikely at dosing for adrenal insufficiency)
Hypokalemia and hypertension
Osteoporosis with long-term use.
Suppression of hypothalamic-pituitary-adrenal (HPA) axis
Peptic ulcer disease or gastrointestinal bleeding.
Opportunistic infections
Myopathy or muscle wasting.
Questions?
If you have any questions or concerns or would like to contribute, please reach out at info@onin.ca
