CHTP Certification Review

Certified Hormone Therapy Pharmacist (CHTP) Review

A Review Guide for the Certified Hormone Therapy Pharmacist (CHTP) Exam

Block 1: Foundations of Endocrinology & Hormone Therapy

A-D

  • AACE: American Association of Clinical Endocrinologists.
  • AMH: Anti-Müllerian Hormone.
  • ASCVD: Atherosclerotic Cardiovascular Disease.
  • BHRT: Bioidentical Hormone Replacement Therapy.
  • BMD: Bone Mineral Density.
  • BPH: Benign Prostatic Hyperplasia.
  • CHC: Combined Hormonal Contraceptive.
  • COC: Combined Oral Contraceptive.
  • CrCl: Creatinine Clearance.
  • DHEA: Dehydroepiandrosterone.

E-H

  • E2: Estradiol.
  • ERT: Estrogen Replacement Therapy.
  • ET: Estrogen Therapy.
  • FDA: Food and Drug Administration.
  • FSH: Follicle-Stimulating Hormone.
  • GAHT: Gender-Affirming Hormone Therapy.
  • GnRH: Gonadotropin-Releasing Hormone.
  • hCG: human Chorionic Gonadotropin.
  • HDL: High-Density Lipoprotein.
  • HPA: Hypothalamic-Pituitary-Adrenal Axis.

I-P

  • IUD: Intrauterine Device.
  • IVF: In Vitro Fertilization.
  • LDL: Low-Density Lipoprotein.
  • LH: Luteinizing Hormone.
  • MHT: Menopausal Hormone Therapy.
  • NAMS: North American Menopause Society.
  • PCOS: Polycystic Ovary Syndrome.
  • POP: Progestin-Only Pill.
  • PSA: Prostate-Specific Antigen.
  • PTH: Parathyroid Hormone.

S-T

  • SERM: Selective Estrogen Receptor Modulator.
  • SHBG: Sex Hormone-Binding Globulin.
  • T3: Triiodothyronine.
  • T4: Thyroxine.
  • TE: Testosterone Enanthate.
  • TC: Testosterone Cypionate.
  • TRT: Testosterone Replacement Therapy.
  • TSH: Thyroid-Stimulating Hormone.
  • TTC: Total Testosterone Concentration.
  • T-score: A measure of bone density.

U-Z

  • USP: United States Pharmacopeia.
  • VMS: Vasomotor Symptoms.
  • VTE: Venous Thromboembolism.
  • WHI: Women's Health Initiative.
  • WPATH: World Professional Association for Transgender Health.
  • DVT: Deep Vein Thrombosis.
  • PE: Pulmonary Embolism.
  • GU: Genitourinary.
  • HRT: Hormone Replacement Therapy (older term for MHT).
  • FTM/F2M: Female-to-Male (transmasculine).

Defining Hormone Therapy

  • Hormone therapy is the use of hormones in medical treatment.
  • It is most often used to replace or supplement naturally occurring hormones that are deficient.
  • It can also be used to suppress natural hormone production.
  • The goal is to restore a more normal physiological state or to achieve a specific therapeutic outcome.
  • This includes a wide range of applications, from menopause management to gender affirmation.
  • A CHTP must have a broad understanding of these diverse applications.
  • The core principle is the targeted manipulation of the endocrine system.

The Benefit-Risk Assessment

  • Every decision to initiate hormone therapy must be based on a careful, individualized benefit-risk assessment.
  • The potential benefits of therapy (e.g., symptom relief) must be weighed against the potential risks (e.g., VTE, cancer).
  • This assessment is not static; it changes over a patient's lifetime.
  • The patient's age, comorbidities, and personal health history are critical factors.
  • The principle of using the lowest effective dose for the shortest duration necessary is a key guiding principle, especially in menopausal hormone therapy.
  • A CHTP is an expert in conducting this benefit-risk assessment.

Patient-Centered Care and Shared Decision-Making

  • The decision to start, continue, or stop hormone therapy is a preference-sensitive one.
  • There is often no single "right" answer.
  • Therefore, shared decision-making (SDM) is the cornerstone of high-quality care.
  • SDM involves the clinician sharing the best available evidence with the patient.
  • It also involves eliciting the patient's values, goals, and preferences.
  • The final decision is made collaboratively.
  • A CHTP must be a skilled communicator and facilitator of these SDM conversations.

The Role of Evidence-Based Medicine

  • All hormone therapy decisions must be grounded in the best available scientific evidence.
  • This includes evidence from large, randomized controlled trials like the Women's Health Initiative (WHI).
  • It also includes recommendations from major professional society guidelines (e.g., NAMS, Endocrine Society).
  • A CHTP must be able to critically appraise this literature.
  • They must be able to distinguish high-quality evidence from low-quality evidence.
  • This evidence-based approach is essential for providing safe and effective care.

The Pharmacist's Role in Hormone Therapy

  • Pharmacists play a vital role in the management of hormone therapy.
  • This includes patient education on the proper use of different formulations.
  • They are responsible for counseling patients on potential side effects and risks.
  • They help to select the most appropriate product based on patient factors and preferences.
  • They are key in monitoring for both safety and efficacy.
  • A CHTP has advanced, specialized knowledge that allows them to be a leader in this clinical area.
  • They often work in collaborative practice with physicians to manage these patients.

Block 2: Core Endocrine Physiology

Overview of the Endocrine System

  • The endocrine system is a network of glands that produce and secrete hormones.
  • Hormones are chemical messengers that travel through the bloodstream to target tissues.
  • Major endocrine glands include the pituitary, thyroid, adrenal glands, pancreas, and gonads (ovaries and testes).
  • This system regulates a wide range of bodily functions, including metabolism, growth, and reproduction.
  • Hormone therapy is the pharmacological manipulation of this complex system.
  • A CHTP must have a strong foundation in basic endocrinology.

The Hypothalamus and Pituitary Gland

  • The hypothalamus and pituitary gland are the "master regulators" of the endocrine system.
  • The hypothalamus, located in the brain, produces releasing and inhibiting hormones.
  • These hormones travel to the anterior pituitary gland, which is located at the base of the brain.
  • In response, the pituitary gland releases its own set of stimulating hormones (e.g., TSH, FSH, LH).
  • These pituitary hormones then travel to the target glands to stimulate the release of the final hormones.
  • This hierarchical structure is known as an "axis."

The Concept of Feedback Loops

  • The endocrine system is regulated by a series of feedback loops.
  • A negative feedback loop is the most common type.
  • In this system, the final hormone (e.g., cortisol) travels back to the hypothalamus and pituitary and inhibits its own production.
  • This creates a stable, self-regulating system.
  • Disruption of these feedback loops is the cause of many endocrine disorders.
  • Exogenous hormone therapy also impacts these feedback loops. For example, taking testosterone will suppress the body's natural production of LH and FSH.
  • A CHTP must understand these feedback mechanisms.

The Hypothalamic-Pituitary-Adrenal (HPA) Axis

  • The HPA axis is the body's central stress response system.
  • The hypothalamus releases CRH (corticotropin-releasing hormone).
  • This stimulates the pituitary to release ACTH (adrenocorticotropic hormone).
  • ACTH then stimulates the adrenal glands to release cortisol.
  • Cortisol has a wide range of effects on the body.
  • Chronic stress can lead to dysregulation of the HPA axis.
  • While not a primary focus of HT, understanding this axis is part of a complete endocrine knowledge base.

The Hypothalamic-Pituitary-Gonadal (HPG) Axis

  • The HPG axis is the central focus of reproductive hormone therapy.
  • The hypothalamus releases GnRH (gonadotropin-releasing hormone).
  • This stimulates the pituitary to release LH (luteinizing hormone) and FSH (follicle-stimulating hormone).
  • In females, LH and FSH act on the ovaries to stimulate estrogen and progesterone production.
  • In males, LH and FSH act on the testes to stimulate testosterone production and spermatogenesis.
  • This axis is the primary target of menopausal hormone therapy, testosterone replacement, and hormonal contraception.

The Menstrual Cycle

  • The menstrual cycle is a complex, cyclical process regulated by the HPG axis.
  • It has two main phases: the follicular phase and the luteal phase.
  • The cycle begins with the start of menses.
  • During the follicular phase, FSH stimulates the growth of an ovarian follicle.
  • This growing follicle produces estrogen.
  • A surge in LH in the middle of the cycle triggers ovulation.
  • After ovulation, the luteal phase begins, and the corpus luteum produces progesterone.
  • If pregnancy does not occur, hormone levels fall, and the cycle begins again.

Estrogens (Estradiol, Estrone, Estriol)

  • Estrogens are the primary female sex hormones.
  • Estradiol (E2): The most potent and predominant estrogen in premenopausal women. It is produced by the ovaries.
  • Estrone (E1): The primary estrogen after menopause. It is produced in peripheral tissues from androgens.
  • Estriol (E3): The primary estrogen during pregnancy.
  • Estrogens have a wide range of effects on the body, including the development of secondary sexual characteristics and the maintenance of bone density.
  • Most estrogen therapy products contain estradiol.

Progestogens (Progesterone and Progestins)

  • Progesterone: The main natural progestogen, produced by the corpus luteum after ovulation. Its primary role is to prepare the uterus for pregnancy.
  • Progestins: Synthetic versions of progesterone.
  • Progestins are a key component of hormonal contraceptives.
  • They are also used in menopausal hormone therapy in women with a uterus to protect the endometrium from the proliferative effects of estrogen.
  • Different progestins have different properties and side effect profiles.

Follicle-Stimulating Hormone (FSH) & Luteinizing Hormone (LH)

  • FSH and LH are the two gonadotropins released by the pituitary gland.
  • FSH: In women, it stimulates the growth of ovarian follicles.
  • LH: In women, the mid-cycle LH surge triggers ovulation.
  • The levels of FSH and LH fluctuate throughout the menstrual cycle.
  • After menopause, as the ovaries stop producing estrogen, the negative feedback is lost, and FSH levels become persistently elevated.
  • An elevated FSH level is a key laboratory marker of menopause.

Androgens in Females

  • While considered "male" hormones, androgens like testosterone and DHEA are also produced in women.
  • They are produced by the ovaries and the adrenal glands.
  • Androgens in women are important for libido, energy, and bone and muscle mass.
  • Excess androgen production can lead to conditions like Polycystic Ovary Syndrome (PCOS).
  • The role of testosterone therapy in women is a controversial and evolving area of practice.

The HPG Axis in Males

  • The HPG axis in males regulates testosterone production and spermatogenesis.
  • GnRH from the hypothalamus stimulates the pituitary to release LH and FSH.
  • LH: Stimulates the Leydig cells in the testes to produce testosterone.
  • FSH: Stimulates the Sertoli cells in the testes and is essential for sperm production.
  • Testosterone then exerts negative feedback on the hypothalamus and pituitary.
  • This maintains a relatively stable level of testosterone.

Testosterone: Production and Effects

  • Testosterone is the primary male sex hormone.
  • It is responsible for the development of male secondary sexual characteristics.
  • It is essential for maintaining libido, erectile function, muscle mass, and bone density.
  • It also has effects on mood, energy, and cognition.
  • Testosterone levels follow a diurnal pattern, with the highest levels in the morning.
  • This is why testosterone levels should always be measured with an early morning blood draw.

Total vs. Free Testosterone

  • Most of the testosterone in the blood is bound to proteins.
  • The majority is bound to Sex Hormone-Binding Globulin (SHBG).
  • A smaller amount is bound to albumin.
  • Only a small fraction (1-2%) is unbound, or "free."
  • The free testosterone is the biologically active form.
  • When assessing a patient for hypogonadism, it is important to measure both total and free testosterone.
  • A patient can have a normal total testosterone but a low free testosterone if their SHBG is high.

Metabolism of Testosterone

  • Testosterone can be metabolized into two other important hormones.
  • Dihydrotestosterone (DHT): Testosterone is converted to DHT by the enzyme 5-alpha reductase. DHT is a more potent androgen and is responsible for things like prostate growth and male pattern baldness.
  • Estradiol: Testosterone is converted to estradiol by the enzyme aromatase. This is the primary source of estrogen in men.
  • This conversion to estradiol is important for bone health and other functions.
  • A CHTP must understand this metabolism, as it has implications for testosterone replacement therapy.

Age-Related Changes in Males

  • Unlike the abrupt hormonal changes of menopause in women, the decline in testosterone in men is very gradual.
  • Total testosterone levels decline by about 1% per year after age 30.
  • SHBG levels tend to increase with age.
  • This combination leads to a more significant decline in free testosterone levels.
  • This gradual decline is sometimes referred to as "andropause," but this term is controversial.
  • The clinical significance of this age-related decline is a major area of debate.

Block 3: Common Indications for Hormone Therapy

Definitions

  • Menopause: The final menstrual period, confirmed after 12 consecutive months of amenorrhea. The average age in the U.S. is 51.
  • Perimenopause: The transitional period before menopause, characterized by hormonal fluctuations and irregular cycles. Can last for several years.
  • Postmenopause: The years following the final menstrual period.
  • Premature Menopause: Menopause that occurs before age 40.
  • A CHTP must be an expert in the terminology and staging of menopause.

Pathophysiology

  • Menopause is caused by the natural depletion of ovarian follicles with age.
  • As the number of follicles declines, the ovaries become less responsive to FSH and LH.
  • This leads to a dramatic decrease in the production of estrogen and progesterone.
  • The loss of negative feedback from estrogen causes the pituitary to release much higher levels of FSH.
  • This hormonal shift is the underlying cause of all the symptoms of menopause.

Vasomotor Symptoms (VMS)

  • VMS, also known as hot flashes and night sweats, are the hallmark symptom of menopause.
  • They are caused by the effect of estrogen withdrawal on the thermoregulatory center in the hypothalamus.
  • They can range from mild to severe and can have a major impact on quality of life and sleep.
  • The presence of moderate to severe VMS is the primary indication for menopausal hormone therapy.
  • A CHTP must be skilled at assessing the severity and impact of VMS.

Genitourinary Syndrome of Menopause (GSM)

  • GSM is a collection of symptoms associated with the decline in estrogen in the vulvovaginal tissues.
  • Symptoms include vaginal dryness, burning, and irritation.
  • It can also lead to painful intercourse (dyspareunia) and an increased risk of urinary tract infections.
  • Unlike VMS, which usually improves over time, GSM is a chronic and progressive condition.
  • It is another major indication for hormone therapy, particularly low-dose local vaginal estrogen.

Diagnosis

  • In a healthy woman over age 45, the diagnosis of perimenopause or menopause is made based on symptoms and menstrual cycle changes.
  • Routine measurement of hormone levels (like FSH) is not necessary or recommended to diagnose menopause in this age group.
  • However, an FSH level may be useful in younger women (<45) with suspected premature menopause.
  • The primary role of the clinician is to rule out other medical causes for the symptoms.
  • A CHTP understands that menopause is a clinical diagnosis.

Definition

  • Male hypogonadism is a clinical syndrome that results from the failure of the testes to produce physiological levels of testosterone and/or a normal number of sperm.
  • It is characterized by both symptoms and a documented low testosterone level.
  • It is important to distinguish this clinical condition from the normal, age-related decline in testosterone.
  • Testosterone replacement therapy is only indicated for men with clinically significant hypogonadism.

Primary vs. Secondary Hypogonadism

  • Primary Hypogonadism: The problem is with the testes themselves. The testes are unable to produce testosterone despite normal or high levels of LH and FSH from the pituitary.
  • An example is Klinefelter syndrome.
  • Secondary Hypogonadism: The problem is with the hypothalamus or pituitary gland. The testes are healthy, but they are not receiving the signal (LH and FSH) to produce testosterone.
  • An example is a pituitary tumor.
  • The pattern of lab results (testosterone, LH, FSH) helps to distinguish between these two types.

Signs and Symptoms

  • The signs and symptoms of low testosterone can be non-specific.
  • Specific Symptoms: Decreased libido, erectile dysfunction, and loss of morning erections.
  • Less Specific Symptoms: Fatigue, depression, decreased muscle mass, and increased body fat.
  • The presence of consistent and bothersome symptoms is a key part of the diagnosis.
  • A CHTP must be skilled at taking a thorough symptom history.

Laboratory Diagnosis

  • The diagnosis of hypogonadism requires biochemical confirmation.
  • This involves measuring an early morning (8-10 AM) total testosterone level on at least two separate occasions.
  • If the total testosterone is low or borderline, a free testosterone level should also be measured.
  • LH and FSH levels should be measured to help distinguish between primary and secondary causes.
  • Other labs, such as prolactin, may also be needed.
  • A CHTP must be an expert at interpreting these lab results.

Contraindications to TRT

  • Before starting testosterone replacement therapy (TRT), it is essential to screen for contraindications.
  • Absolute contraindications include a history of prostate or breast cancer.
  • Other contraindications include a high hematocrit, severe untreated sleep apnea, or uncontrolled heart failure.
  • A baseline prostate-specific antigen (PSA) and hematocrit should be checked.
  • A CHTP is responsible for ensuring this baseline safety screening has been completed.

Mechanisms of Combined Hormonal Contraceptives (CHCs)

  • CHCs contain both an estrogen and a progestin.
  • Their primary mechanism of action is the suppression of ovulation.
  • The exogenous hormones provide negative feedback to the HPG axis.
  • This suppresses the release of FSH and prevents the development of an ovarian follicle.
  • It also suppresses the mid-cycle LH surge, which is the direct trigger for ovulation.
  • Secondary mechanisms include thickening of the cervical mucus (making it harder for sperm to penetrate) and thinning of the endometrium.

The Role of Estrogen in CHCs

  • The primary role of the estrogen component (usually ethinyl estradiol) is to stabilize the endometrium and prevent irregular bleeding.
  • It also contributes to the suppression of FSH.
  • However, the estrogen component is responsible for many of the side effects and most of the serious risks of CHCs, such as VTE.
  • Modern CHCs use the lowest possible dose of estrogen that still provides good cycle control.

The Role of Progestin in CHCs

  • The progestin component is the primary driver of the contraceptive effect.
  • It is responsible for suppressing the LH surge.
  • It is also responsible for thickening the cervical mucus.
  • There are many different generations of progestins.
  • These different progestins have varying degrees of androgenic and other hormonal activity.
  • The specific progestin in a CHC determines its side effect profile.
  • A CHTP must be familiar with the properties of the different progestins.

Mechanisms of Progestin-Only Contraceptives

  • Progestin-only methods do not contain estrogen.
  • Progestin-Only Pills (POPs or "minipills"): Their primary mechanism is thickening of the cervical mucus. They do not reliably suppress ovulation. They must be taken at the same time every day to be effective.
  • Progestin Injection (DMPA): Reliably suppresses ovulation.
  • Progestin Implant and IUDs: Primarily work by thickening cervical mucus, but can also suppress ovulation.
  • These methods are a key option for women who have a contraindication to estrogen.

Emergency Contraception

  • Emergency contraception works by preventing or delaying ovulation.
  • It is not effective if ovulation has already occurred.
  • Levonorgestrel (Plan B): A high-dose progestin. Most effective when taken as soon as possible after unprotected intercourse.
  • Ulipristal Acetate (ella): A selective progesterone receptor modulator. It is more effective than levonorgestrel, especially closer to the time of ovulation.
  • Copper IUD: The most effective form of emergency contraception. It can be inserted up to 5 days after unprotected intercourse.
  • A CHTP should be an expert on these options.

The Role of the Pharmacist in Transgender Care

  • Pharmacists are a key part of the multidisciplinary team providing care to transgender and gender diverse individuals.
  • They are responsible for dispensing and counseling on GAHT.
  • They play a role in patient education, monitoring, and advocacy.
  • It is essential to create a welcoming and affirming pharmacy environment.
  • This includes using the patient's correct name and pronouns.
  • A CHTP must be a culturally competent and knowledgeable provider for this population.

The WPATH Standards of Care

  • The World Professional Association for Transgender Health (WPATH) publishes the Standards of Care (SOC).
  • The SOC provides clinical guidance for the health of transgender and gender diverse people.
  • It is the globally recognized, evidence-based standard for this field.
  • It outlines the criteria for initiating GAHT and the recommendations for monitoring.
  • A CHTP must be an expert on the WPATH SOC.
  • Adherence to these standards is the basis of high-quality care.

Goals of Feminizing Hormone Therapy

  • The goal of feminizing therapy is to induce female secondary sexual characteristics and to suppress male secondary sexual characteristics.
  • This is achieved by using estrogen to induce feminization and an anti-androgen to block the effects of testosterone.
  • The physical changes desired include breast development, skin softening, and a redistribution of body fat.
  • The goal is to align the patient's physical appearance with their gender identity.
  • The hormonal goal is to bring the patient's testosterone and estrogen levels into the normal physiologic range for a cisgender female.

Goals of Masculinizing Hormone Therapy

  • The goal of masculinizing therapy is to induce male secondary sexual characteristics and to suppress female secondary sexual characteristics.
  • This is achieved by using testosterone.
  • The physical changes desired include facial and body hair growth, deepening of the voice, and cessation of menses.
  • It also leads to an increase in muscle mass and a redistribution of body fat.
  • The goal is to align the patient's physical appearance with their gender identity.
  • The hormonal goal is to bring the patient's testosterone level into the normal physiologic range for a cisgender male.

Informed Consent Model of Care

  • The informed consent model is an approach to initiating GAHT that does not require a letter from a mental health professional.
  • It is based on the principle that transgender individuals have the right to make their own decisions about their bodies.
  • The role of the clinician is to ensure the patient fully understands the risks and benefits of therapy and is able to provide informed consent.
  • This model has become the standard of care in many specialized clinics.
  • It reduces barriers to care for transgender individuals.
  • A CHTP should be familiar with this model of care.

The Hypothalamic-Pituitary-Thyroid (HPT) Axis

  • The HPT axis regulates the production of thyroid hormone.
  • The hypothalamus releases TRH (thyrotropin-releasing hormone).
  • This stimulates the pituitary to release TSH (thyroid-stimulating hormone).
  • TSH then stimulates the thyroid gland to produce and release thyroid hormones (T4 and T3).
  • T4 and T3 then provide negative feedback to the hypothalamus and pituitary.
  • A CHTP must understand this axis to interpret thyroid function tests.

Thyroid Hormones (T4 and T3)

  • The thyroid gland produces two main hormones.
  • Thyroxine (T4): The primary hormone produced by the thyroid. It is considered a prohormone.
  • Triiodothyronine (T3): The more biologically active hormone. Most T3 is produced by the conversion of T4 to T3 in the peripheral tissues.
  • These hormones regulate the body's metabolism.
  • They are essential for normal growth and development.

Hypothyroidism

  • Hypothyroidism is a condition where the thyroid gland does not produce enough thyroid hormone.
  • The most common cause in the U.S. is Hashimoto's disease, an autoimmune condition.
  • Symptoms include fatigue, weight gain, cold intolerance, and constipation.
  • The classic lab finding is a high TSH and a low free T4.
  • The high TSH is because the pituitary is trying to stimulate a failing thyroid gland.
  • The treatment is thyroid hormone replacement therapy.

Hyperthyroidism

  • Hyperthyroidism is a condition where the thyroid gland produces too much thyroid hormone.
  • The most common cause is Graves' disease, an autoimmune condition where an antibody stimulates the TSH receptor.
  • Symptoms include weight loss, heat intolerance, anxiety, and a rapid heart rate.
  • The classic lab finding is a low TSH and a high free T4.
  • The TSH is low due to the negative feedback from the high T4 levels.
  • Treatment involves antithyroid drugs, radioactive iodine, or surgery.

Thyroid Function Tests (TFTs)

  • TSH: The single most important test for assessing thyroid function. It is the first test to become abnormal.
  • Free T4: Measures the unbound, active form of thyroxine.
  • Total T4: Measures both bound and unbound T4. Can be affected by protein levels.
  • Free T3: Sometimes measured to assess for T3 toxicosis.
  • A CHTP must be an expert at interpreting these key lab tests.
  • The pattern of TSH and free T4 is used to diagnose and monitor thyroid disorders.

Block 4: Pharmacotherapy for Menopause & Hypogonadism

Indications for MHT

  • The primary indication for systemic MHT is the treatment of moderate to severe vasomotor symptoms (VMS).
  • Another key indication is the treatment of moderate to severe symptoms of vulvar and vaginal atrophy (Genitourinary Syndrome of Menopause - GSM).
  • MHT is also approved for the prevention of postmenopausal osteoporosis.
  • However, it is generally not recommended as a first-line therapy for osteoporosis alone due to the risks.
  • It should only be considered for osteoporosis prevention in women with significant risk who cannot take other agents.
  • The decision to use MHT should be individualized based on the patient's symptoms and benefit-risk profile.

Estrogen Formulations

  • Oral Estrogens: Conjugated equine estrogens (CEE), synthetic conjugated estrogens, micronized estradiol.
  • Transdermal Estrogens: Estradiol patches, gels, sprays. These avoid the first-pass metabolism in the liver.
  • Transdermal delivery is associated with a lower risk of VTE compared to oral estrogen.
  • Vaginal Estrogens: Low-dose creams, tablets, and rings used for the local treatment of GSM. These have minimal systemic absorption.
  • The choice of formulation depends on the patient's preference and risk factors.
  • A CHTP must be an expert on the pros and cons of each formulation.

The Role of Progestogens

  • In a woman with an intact uterus, unopposed estrogen therapy significantly increases the risk of endometrial hyperplasia and cancer.
  • Therefore, a progestogen must always be added to systemic estrogen therapy in these women.
  • The progestogen opposes the proliferative effect of estrogen on the endometrium.
  • Continuous Combined Therapy: Estrogen and progestogen are taken every day. This leads to endometrial atrophy and amenorrhea.
  • Continuous Sequential Therapy: Estrogen is taken daily, and the progestogen is added for 12-14 days each month. This results in a scheduled monthly bleed.
  • Women who have had a hysterectomy do not need a progestogen.

Progestogen Formulations

  • Micronized Progesterone: Chemically identical to human progesterone. It is often preferred due to a potentially better safety profile regarding breast cancer and cardiovascular risk.
  • Medroxyprogesterone Acetate (MPA): The most commonly studied synthetic progestin in MHT.
  • Norethindrone, Levonorgestrel: Other synthetic progestins used in combination patches.
  • Levonorgestrel-releasing IUD: Can be used for endometrial protection as an off-label alternative.
  • A CHTP must understand the differences between these options.

Initiation and Monitoring

  • The general principle is to use the lowest effective dose for the shortest duration consistent with the patient's treatment goals.
  • MHT is most appropriate for women who are within 10 years of menopause or younger than age 60.
  • A thorough baseline assessment, including a personal and family medical history, is essential.
  • Blood pressure should be checked, and a recent mammogram should be on file.
  • Routine monitoring of hormone levels is not recommended.
  • Follow-up should occur annually to reassess the benefits and risks and to consider if continuation is still appropriate.

Goals of TRT

  • The goal of TRT is to restore testosterone levels to the normal physiologic range.
  • This is done to improve the signs and symptoms of hypogonadism.
  • The goal is not to achieve supraphysiologic (abnormally high) levels.
  • Key therapeutic goals include improvement in libido, energy levels, and mood.
  • It can also help to improve muscle mass and bone mineral density.
  • The therapy should be guided by both symptom improvement and laboratory monitoring.

Transdermal Gels and Solutions

  • Transdermal gels are the most commonly prescribed form of TRT.
  • They are applied once daily to the skin.
  • They provide relatively stable testosterone levels throughout the day.
  • A major disadvantage is the risk of transference to a partner or child through skin-to-skin contact.
  • Patients must be counseled to cover the application site and to wash their hands thoroughly.
  • Transdermal patches are another option, but they can cause significant skin irritation.

Intramuscular Injections

  • Injectable testosterone (cypionate or enanthate) is a common and cost-effective option.
  • It is typically injected every 1-2 weeks.
  • This can be done in a clinician's office or self-injected by the patient at home.
  • A major disadvantage is that it can cause large peaks and troughs in testosterone levels.
  • This can lead to fluctuations in mood, energy, and libido ("rollercoaster effect").
  • Longer-acting injections (e.g., testosterone undecanoate) are available that are given less frequently.

Other Formulations

  • Subcutaneous Pellets: Small pellets are implanted under the skin and release testosterone slowly over 3-6 months. This requires an in-office procedure.
  • Nasal Gel: A gel that is applied to the inside of the nostrils multiple times per day.
  • Oral Capsules: A newer oral formulation (testosterone undecanoate) is available that is absorbed through the lymphatic system, avoiding liver toxicity.
  • Older oral formulations (methyltestosterone) are not recommended due to the risk of hepatotoxicity.
  • A CHTP must be knowledgeable about the pros and cons of all these delivery systems.

Monitoring TRT

  • Ongoing monitoring is essential for both safety and efficacy.
  • Testosterone levels should be checked 3-6 months after starting therapy and then annually.
  • The goal is to maintain the total testosterone level in the mid-normal range for a young, healthy man.
  • Hematocrit must be monitored at baseline, at 3-6 months, and then annually. TRT can cause erythrocytosis (high red blood cell count), which increases the risk of blood clots.
  • PSA should be monitored in men over 40.
  • A CHTP is often responsible for managing this monitoring plan.

Goals of Therapy

  • The goal of feminizing GAHT is to induce the development of female secondary sexual characteristics and to suppress male characteristics.
  • This is achieved by using estrogen and, in most cases, an anti-androgen.
  • The hormonal goal is to suppress serum testosterone into the normal female range (<50 ng/dL) and to achieve an estradiol level in the normal female range.
  • This therapy is a lifelong commitment for most individuals.
  • A CHTP must be an expert in the pharmacology of these regimens.

Estrogen Formulations

  • The primary estrogen used is 17-beta estradiol, which is bioidentical.
  • Oral/Sublingual Estradiol: The most common starting method. Sublingual administration can help to bypass some first-pass metabolism.
  • Transdermal Patches: Provide more stable hormone levels and avoid the first-pass effect, which may reduce VTE risk.
  • Intramuscular Injections (Estradiol Valerate or Cypionate): Provide higher peak levels and are given every 1-2 weeks.
  • Ethinyl estradiol (found in birth control pills) is not recommended due to a higher risk of VTE.

Anti-Androgens

  • Anti-androgens are used to block the production or effects of testosterone.
  • Spironolactone: The most commonly used anti-androgen in the U.S. It is a diuretic that also has anti-androgenic effects. Requires monitoring of potassium and renal function.
  • Finasteride/Dutasteride: 5-alpha reductase inhibitors. They block the conversion of testosterone to DHT and are primarily used to treat male pattern hair loss.
  • GnRH Agonists (e.g., leuprolide): The most effective at suppressing testosterone, but also very expensive.
  • Bicalutamide and cyproterone acetate are used in other countries but less commonly in the U.S.

Progestogens

  • The role of progestogens in feminizing therapy is controversial.
  • Some evidence suggests that it may help with breast development and libido, but the data is limited.
  • There are also potential risks, such as an increased risk of VTE and negative effects on mood.
  • Micronized progesterone is the most commonly used agent if a progestogen is desired.
  • A CHTP must be able to have a nuanced discussion about the potential benefits and risks of adding a progestogen.

Monitoring Feminizing Therapy

  • Regular monitoring is essential for safety and efficacy.
  • Hormone levels (total testosterone and estradiol) should be checked every 3 months for the first year and then 1-2 times per year.
  • For patients on spironolactone, potassium and creatinine should be monitored.
  • Prolactin levels should be monitored, as estrogen can cause an elevation.
  • Routine screening for cardiovascular risk factors (lipids, blood pressure) and bone health should be conducted.
  • A CHTP is a key part of this ongoing monitoring plan.

Block 5: Contraception & Gender-Affirming Care

Formulations

  • CHCs contain both an estrogen (usually ethinyl estradiol) and a progestin.
  • Oral Contraceptives (COCs): The most common form. Available as monophasic, biphasic, or triphasic pills.
  • Transdermal Patch: Applied weekly.
  • Vaginal Ring: Inserted monthly.
  • The patch and ring provide more stable hormone levels than the pill and bypass first-pass metabolism.
  • A CHTP must be an expert on the different delivery systems.

The Role of the Progestin

  • There are multiple generations of progestins used in CHCs.
  • The specific progestin determines the side effect profile of the pill.
  • Older progestins (e.g., levonorgestrel) have more androgenic activity.
  • Newer progestins (e.g., drospirenone) are anti-androgenic, which can be helpful for acne.
  • Drospirenone also has anti-mineralocorticoid activity and carries a slightly higher risk of VTE.
  • A CHTP uses their knowledge of these differences to help select the best product for a patient.

Initiation and Dosing Regimens

  • A "Quick Start" method (starting the day of the appointment) is now preferred over the traditional Sunday start.
  • Traditional regimens involve 21 days of active pills followed by a 7-day placebo week, which induces a withdrawal bleed.
  • Extended-cycle regimens (e.g., 84 days of active pills) reduce the number of withdrawal bleeds to four times a year.
  • Continuous-use regimens eliminate the placebo pills altogether, stopping withdrawal bleeds entirely.
  • A CHTP can counsel patients on these different regimen options.

Contraindications and The MEC

  • The Centers for Disease Control (CDC) publishes the U.S. Medical Eligibility Criteria for Contraceptive Use (MEC).
  • This is the evidence-based guideline for contraceptive safety.
  • It categorizes conditions based on their level of risk (Category 1 = no restriction, Category 4 = unacceptable risk).
  • Absolute contraindications to CHCs (Category 4) include a history of VTE, stroke, certain migraines, and smoking over age 35.
  • A CHTP must be an expert at using the MEC to screen patients for contraindications.

Managing Side Effects

  • Common side effects include nausea, breast tenderness, and breakthrough bleeding.
  • These often improve after the first three months.
  • The side effect profile can be managed by switching to a pill with a different progestin or a different estrogen dose.
  • For example, if a patient is experiencing androgenic side effects like acne, switching to a pill with a less androgenic progestin can help.
  • A CHTP is skilled at troubleshooting and managing these common side effects.

Progestin-Only Pills (POPs)

  • POPs (or "minipills") contain only a progestin and no estrogen.
  • They are a key option for women who have contraindications to estrogen (e.g., smokers over 35, history of VTE).
  • Their primary mechanism is thickening the cervical mucus.
  • They must be taken at the same time every day to be effective; there is only a 3-hour window.
  • The main side effect is irregular bleeding.

Injectable Contraception (DMPA)

  • Depot medroxyprogesterone acetate (DMPA or "the shot") is a progestin-only injection given every 3 months.
  • It is a highly effective contraceptive because it reliably suppresses ovulation.
  • A key side effect is irregular bleeding, which often improves over time, with many women becoming amenorrheic after one year.
  • There is a Black Box Warning about a potential loss of bone mineral density with long-term use. This is generally reversible after stopping.

Contraceptive Implant

  • The etonogestrel implant (Nexplanon) is a type of Long-Acting Reversible Contraceptive (LARC).
  • It is a small, flexible rod inserted under the skin of the upper arm.
  • It releases a progestin and is effective for 3 years.
  • It is one of the most effective forms of contraception available.
  • The main reason for discontinuation is irregular bleeding patterns.

Hormonal Intrauterine Devices (IUDs)

  • Hormonal IUDs (e.g., Mirena, Kyleena) are another type of LARC.
  • They are T-shaped devices inserted into the uterus that release a small amount of levonorgestrel.
  • They are effective for 5-8 years, depending on the device.
  • They primarily work locally by thickening cervical mucus and thinning the endometrium.
  • They are highly effective and often lead to much lighter periods or no periods at all.

The Importance of LARCs

  • LARCs (implants and IUDs) are considered first-line contraceptive options for most women by major medical organizations.
  • This is because their effectiveness is not dependent on user adherence.
  • They have "perfect use" and "typical use" effectiveness rates that are nearly identical.
  • They are highly effective, safe, and cost-effective over the long term.
  • A CHTP should be a strong advocate for increasing access to and education about LARCs.

Monitoring Feminizing Therapy

  • Routine lab monitoring is essential for both safety and efficacy.
  • Hormone Levels: Total testosterone and estradiol should be checked every 3 months for the first year, then 1-2 times per year. The goal is to maintain levels in the normal physiologic female range.
  • Potassium and Creatinine: For patients on spironolactone.
  • Prolactin: Estrogen can cause hyperprolactinemia.
  • Routine health screenings (e.g., for lipids and diabetes) should also be conducted.
  • Bone density screening should be considered, especially in individuals with a history of low hormone levels.

Common Side Effects of Feminizing Therapy

  • VTE Risk: Estrogen, particularly oral estrogen, increases the risk of VTE. This is the most serious risk. Transdermal estrogen is preferred to mitigate this risk.
  • Mood Changes: Can occur with any hormone therapy.
  • Weight Gain: Due to redistribution of body fat.
  • Decreased Libido: A common effect of testosterone suppression.
  • Side effects of spironolactone can include polyuria and postural dizziness.
  • A CHTP is an expert at counseling on and managing these side effects.

Monitoring Masculinizing Therapy

  • Hormone Levels: Total testosterone should be checked every 3 months for the first year. The goal is to maintain levels in the normal physiologic male range.
  • The timing of the lab draw is critical and depends on the formulation (e.g., mid-cycle for bi-weekly injections).
  • Hematocrit and Hemoglobin: Testosterone can cause erythrocytosis (an increase in red blood cells). This must be monitored closely, as a high hematocrit increases the risk of blood clots.
  • Liver function tests should be monitored, especially with oral formulations (which are not typically used).
  • Routine screening for cardiovascular risk is important.

Common Side Effects of Masculinizing Therapy

  • Erythrocytosis: The most common and serious side effect. If the hematocrit gets too high, the testosterone dose may need to be lowered or the dosing interval changed.
  • Acne and Oily Skin: A very common androgenic side effect.
  • Male Pattern Baldness: Can occur in individuals with a genetic predisposition.
  • Vaginal Atrophy: Can occur due to the suppression of estrogen.
  • Mood Changes: Can be related to the "peak and trough" effect of injections.
  • A CHTP is responsible for monitoring for and managing these side effects.

Long-Term Health Considerations

  • A key part of the CHTP's role is to ensure that transgender individuals receive all appropriate, routine preventive health screenings.
  • This requires an understanding of which screenings are needed based on the individual's anatomy.
  • For example, a transmasculine individual who has not had a hysterectomy still needs cervical cancer screening.
  • A transfeminine individual needs prostate cancer screening according to standard guidelines.
  • Breast cancer screening is also important for transfeminine individuals on long-term estrogen.
  • The CHTP helps to coordinate and advocate for this comprehensive preventive care.

Block 6: Risk Assessment & Mitigation

Hormones and Bone Metabolism

  • Estrogen and testosterone play a critical role in maintaining bone mineral density (BMD).
  • These hormones inhibit the activity of osteoclasts, the cells that break down bone.
  • The rapid decline in estrogen at menopause is a major cause of accelerated bone loss in women.
  • Similarly, hypogonadism in men leads to an increased risk of osteoporosis.
  • A CHTP must understand this fundamental physiological link.

MHT for Osteoporosis Prevention

  • Systemic MHT is FDA-approved for the prevention of postmenopausal osteoporosis.
  • It is very effective at preserving BMD and reducing fracture risk in early postmenopausal women.
  • However, due to the risks identified in the WHI, it is not a first-line therapy for osteoporosis alone.
  • It is a reasonable option for women who also have vasomotor symptoms.
  • For women with premature menopause, MHT is essential to prevent early-onset osteoporosis.

TRT and Bone Health in Men

  • In men with confirmed hypogonadism and osteoporosis, testosterone replacement therapy can improve bone mineral density.
  • Testosterone has a direct effect on bone and is also aromatized to estrogen, which is crucial for male bone health.
  • Routine BMD screening is recommended for all men with hypogonadism.
  • A CHTP monitors BMD as a key outcome of TRT.

GAHT and Bone Health

  • Maintaining bone health is a key consideration in gender-affirming hormone therapy.
  • The goal is to ensure that the individual is always on an adequate dose of either estrogen or testosterone to protect their bones.
  • Inadequate hormone levels, especially after gonadectomy, can lead to rapid bone loss.
  • Regular monitoring of hormone levels is essential.
  • A CHTP plays a key role in ensuring that the GAHT regimen is bone-protective.

Screening and Assessment

  • BMD is measured using a dual-energy x-ray absorptiometry (DXA) scan.
  • The results are reported as a T-score, which compares the patient's BMD to that of a young, healthy adult.
  • A T-score of -2.5 or lower indicates osteoporosis.
  • The FRAX tool can be used to calculate a patient's 10-year risk of a major osteoporotic fracture.
  • A CHTP should be familiar with these key assessment tools.

The Women's Health Initiative (WHI) Trial

  • The WHI was a large randomized controlled trial that had a profound impact on the understanding of MHT.
  • The trial was stopped early because the estrogen-plus-progestin arm showed a small increased risk of coronary heart disease, stroke, VTE, and breast cancer.
  • This led to a dramatic decrease in the use of MHT.
  • A CHTP must have a deep understanding of the findings of the WHI.

The "Timing Hypothesis"

  • Subsequent analyses of the WHI data have led to the "timing hypothesis."
  • This hypothesis suggests that the cardiovascular effects of MHT depend on when it is started relative to menopause.
  • In younger, newly menopausal women (age 50-59), MHT appears to have a neutral or even a slightly beneficial effect on heart disease.
  • However, in older women who are more than 10 years past menopause, starting MHT may increase cardiovascular risk.
  • This is a key concept that guides modern MHT prescribing.

Assessing ASCVD Risk

  • Before starting MHT, a woman's baseline risk for atherosclerotic cardiovascular disease (ASCVD) should be assessed.
  • The Pooled Cohort Equation is a commonly used tool to calculate the 10-year ASCVD risk.
  • MHT is generally not recommended for women at high ASCVD risk.
  • A CHTP must be able to use this risk calculator as part of their patient assessment.

Route of Administration Matters

  • Observational studies suggest that the route of estrogen administration impacts cardiovascular risk.
  • Transdermal estrogen appears to have a more favorable or neutral effect on cardiovascular risk compared to oral estrogen.
  • This is because it avoids the first-pass effect in the liver and has less of an impact on clotting factors.
  • For women with moderate cardiovascular risk, a transdermal formulation is preferred.

Testosterone and Cardiovascular Risk

  • The cardiovascular safety of testosterone replacement therapy is a major area of debate.
  • Some observational studies have suggested a potential increased risk, while others have not.
  • Large, long-term randomized controlled trials are still needed.
  • Current guidelines recommend that TRT be used with caution in men with a history of cardiovascular disease.
  • A CHTP must have a nuanced discussion with patients about this uncertain risk.

Mechanism of VTE Risk

  • Estrogen has prothrombotic effects.
  • It increases the production of clotting factors in the liver.
  • This effect is most pronounced with oral estrogens, due to the first-pass metabolism.
  • This increased tendency to clot is what leads to the elevated risk of VTE (DVT and PE).
  • The risk is dose-dependent.
  • A CHTP must understand this mechanism to counsel patients.

VTE Risk with MHT

  • Oral MHT is associated with a 2- to 3-fold increased risk of VTE.
  • While the relative risk is increased, the absolute risk in healthy, young postmenopausal women is still very low.
  • The risk is highest in the first year of use.
  • Observational data suggests that transdermal estrogen at standard doses is not associated with an increased risk of VTE.
  • Therefore, for women with risk factors for VTE (like obesity), a transdermal route is strongly preferred.

VTE Risk with CHCs

  • Combined hormonal contraceptives also increase the risk of VTE.
  • The risk varies depending on the dose of estrogen and the type of progestin.
  • The risk is highest with pills that contain the progestin drospirenone.
  • However, the absolute risk of VTE with any CHC is still much lower than the risk of VTE during pregnancy and the postpartum period.
  • A CHTP must be an expert at screening for VTE risk factors using the CDC MEC.

VTE Risk with GAHT

  • Feminizing hormone therapy with estrogen also increases the risk of VTE.
  • Similar to MHT, the risk appears to be lower with transdermal estrogen compared to oral.
  • This is why transdermal is often the preferred route, especially in older individuals or those with other risk factors.
  • Masculinizing therapy with testosterone can increase the hematocrit, which can also increase the risk of VTE.
  • Monitoring of hematocrit is a key safety parameter.

Risk Factor Assessment

  • Before initiating any estrogen-containing therapy, a thorough assessment for VTE risk factors is mandatory.
  • Key risk factors include a personal history of VTE, a known thrombophilia (clotting disorder), obesity, smoking, and older age.
  • The CDC MEC provides a systematic framework for this assessment for contraceptives.
  • The principles can be applied to all forms of hormone therapy.
  • A CHTP is responsible for ensuring this risk assessment is performed and documented.

Breast Cancer Risk with MHT

  • This is one of the most feared risks of MHT.
  • The WHI found a small increased risk of breast cancer with long-term ( >5 years) use of combined estrogen-progestin therapy.
  • The risk appears to be primarily associated with the progestin component.
  • In the WHI, estrogen-only therapy (in women without a uterus) did not increase the risk of breast cancer and may have even slightly decreased it.
  • The use of micronized progesterone may be associated with a lower risk than synthetic progestins.
  • A CHTP must be able to accurately communicate these nuanced risks to patients.

Endometrial Cancer Risk with MHT

  • This is the risk of unopposed estrogen therapy in a woman with a uterus.
  • Estrogen causes the lining of the uterus (the endometrium) to grow.
  • Without a progestogen to oppose this effect, this can lead to endometrial hyperplasia and cancer.
  • This risk is completely negated by the addition of an adequate dose of a progestogen.
  • This is the most important principle of safe MHT prescribing.
  • A CHTP must always ensure that a woman with a uterus who is on systemic estrogen is also on a progestogen.

Prostate Cancer Risk with TRT

  • Historically, there has been a concern that TRT could cause or worsen prostate cancer.
  • However, current evidence does not support this.
  • TRT does not appear to increase the risk of developing prostate cancer.
  • However, it is contraindicated in men with a known, active prostate cancer because it can stimulate its growth.
  • Men should be appropriately screened for prostate cancer before starting TRT.
  • Ongoing monitoring with a PSA is also recommended.
  • A CHTP must be up-to-date on this evolving evidence.

Cancer Risk with GAHT

  • The long-term data on cancer risk with GAHT is still limited.
  • For transfeminine individuals, there is an increased risk of breast cancer compared to cisgender men, but it is likely lower than for cisgender women.
  • Prostate cancer risk is thought to be very low.
  • For transmasculine individuals, the risk of breast, ovarian, and uterine cancer must be considered if these organs have not been surgically removed.
  • Long-term testosterone use can cause vaginal atrophy, which can make cervical cancer screening difficult.
  • A CHTP must be able to counsel patients on these risks and the importance of routine cancer screening.

Risk Counseling

  • Communicating these cancer risks is a key part of the shared decision-making process.
  • It is important to present the risks in terms of absolute numbers, not just relative risks, as the absolute risks are often very small.
  • The risks must always be balanced against the potential benefits of therapy.
  • For a woman with severe, debilitating vasomotor symptoms, the small increased risk of breast cancer may be an acceptable trade-off.
  • A CHTP must be skilled at this nuanced risk communication.

Defining "Bioidentical"

  • The term "bioidentical" means that the hormone is chemically identical to the one produced by the human body.
  • For example, 17-beta estradiol is a bioidentical estrogen. Micronized progesterone is a bioidentical progesterone.
  • It is important to note that many FDA-approved MHT products contain bioidentical hormones.
  • The term is often used, however, to refer to custom-compounded BHRT preparations.
  • A CHTP must be precise with this terminology.

Custom-Compounded BHRT

  • This refers to BHRT preparations that are made by a compounding pharmacy for a specific patient.
  • They are often marketed as being more "natural" or "individualized" than FDA-approved products.
  • They are often prescribed based on the results of salivary hormone testing.
  • The use of custom-compounded BHRT is highly controversial.
  • A CHTP must understand the evidence and controversies surrounding this practice.

The Controversy: Safety and Efficacy

  • Major medical organizations, including NAMS and the Endocrine Society, do not recommend custom-compounded BHRT.
  • There is a lack of evidence for the safety and efficacy of these compounded products.
  • Because they are not FDA-approved, they have not undergone rigorous testing for purity, potency, or stability.
  • There is particular concern that compounded progesterone creams may not provide adequate protection for the endometrium.
  • The practice of using salivary hormone testing to guide dosing is not supported by scientific evidence.

Patient Counseling and Education

  • Many patients are drawn to BHRT due to marketing that claims it is safer and more natural.
  • A CHTP has a key role in providing evidence-based education to these patients.
  • This involves explaining the difference between FDA-approved bioidentical products and custom-compounded products.
  • It involves explaining the lack of safety data for compounded preparations.
  • The conversation should be respectful of the patient's desire for a "natural" approach, while also providing accurate information.

The Pharmacist's Professional Responsibility

  • A pharmacist who compounds BHRT has specific professional responsibilities.
  • They must comply with all state and federal regulations for compounding, including USP standards.
  • They must not make any unsubstantiated claims about the safety or efficacy of their products.
  • They have a duty to provide their patients with accurate information.
  • A CHTP must always practice in an evidence-based manner, whether they are dispensing an FDA-approved product or a compounded preparation.

Block 7: Advanced Topics & Final Review

Principles of Shared Decision-Making (SDM)

  • SDM is a collaborative process where clinicians and patients work together to make healthcare decisions.
  • It involves sharing the best available evidence with the patient.
  • It also involves eliciting the patient's values and preferences.
  • The final decision is based on a combination of the evidence and what matters most to the patient.
  • This is the ideal model for making all hormone therapy decisions.

Communicating Risks and Benefits

  • A key part of SDM is communicating the potential risks and benefits of hormone therapy.
  • This must be done in a clear, simple, and unbiased way.
  • Using absolute numbers (e.g., "3 extra women out of 10,000") is more effective than using relative numbers (e.g., "a 30% increased risk").
  • Patient decision aids are tools (e.g., pamphlets, videos) that can help to present this information in an accessible way.
  • A CHTP must be skilled at this type of risk communication.

Counseling on Different Formulations

  • A CHTP must be able to explain the pros and cons of the different hormone formulations.
  • This includes counseling on the proper administration technique for patches, gels, injections, and vaginal products.
  • The conversation should be tailored to the patient's lifestyle and preferences.
  • For example, a patch may be more convenient for some, while a gel may be preferred by others.
  • This counseling helps the patient to choose the method they are most likely to use correctly.

Setting Expectations

  • It is important to set realistic expectations with the patient.
  • This includes explaining the expected timeline for symptom improvement.
  • It also involves counseling on the common, non-serious side effects that may occur, especially in the first few months.
  • This can help to prevent early discontinuation of therapy.
  • The CHTP plays a key role in setting these expectations.

Ongoing Follow-Up

  • The conversation does not end when the prescription is dispensed.
  • A CHTP is involved in the ongoing follow-up with the patient.
  • This includes checking in to see how the patient is tolerating the therapy.
  • It involves assessing for both efficacy and side effects.
  • This ongoing dialogue is a key part of safe and effective long-term management.
  • It reinforces the collaborative partnership between the patient and the pharmacist.

Monitoring MHT

  • Routine monitoring of hormone levels is not recommended for women on MHT. Dosing is based on symptom relief.
  • An annual follow-up visit is recommended.
  • This visit should include a reassessment of symptoms and a discussion of the ongoing benefits and risks.
  • Blood pressure should be checked.
  • The patient should be reminded about the importance of their routine health screenings, including mammograms.
  • Any unexpected vaginal bleeding must be evaluated immediately.

Monitoring TRT

  • Monitoring of TRT is essential for safety and efficacy.
  • Total testosterone levels should be checked 3-6 months after initiation, and then annually.
  • The goal is to achieve a level in the mid-normal range.
  • Hematocrit must be checked at baseline, 3-6 months, and annually to screen for erythrocytosis.
  • PSA should be monitored in men over 40.
  • A CHTP is responsible for tracking this monitoring schedule.

Monitoring Feminizing GAHT

  • Estradiol and testosterone levels should be checked every 3 months for the first year, then 1-2 times per year.
  • The goal is to maintain levels in the physiologic female range.
  • For patients on spironolactone, serum potassium and creatinine should be monitored.
  • Prolactin levels should be checked annually.
  • Long-term monitoring includes screening for cardiovascular risk and bone density.

Monitoring Masculinizing GAHT

  • Testosterone levels should be checked every 3 months for the first year, then 1-2 times per year.
  • The goal is to maintain levels in the physiologic male range.
  • Hematocrit and hemoglobin must be checked every 3 months for the first year, and then annually.
  • This is the most important safety monitoring parameter.
  • If the hematocrit is >54%, the testosterone dose needs to be adjusted.
  • Lipids and A1c should also be monitored.

The Pharmacist's Role in Monitoring

  • A CHTP often has a key role in managing this monitoring under a collaborative practice agreement.
  • This can include ordering the necessary labs.
  • They are responsible for interpreting the lab results in the context of the patient's therapy.
  • They can then make dose adjustments according to the protocol.
  • This pharmacist-led service ensures that monitoring is done consistently and that results are acted upon in a timely manner.

Menopause Rating Scale (MRS)

  • An assessment tool used to measure the severity of menopausal symptoms and their impact on quality of life.
  • It is a patient-completed questionnaire.
  • It includes subscales for somatic, psychological, and urogenital symptoms.
  • A CHTP can use this tool to get a baseline assessment of a patient's symptom burden and to track their response to therapy over time.

FRAX® (Fracture Risk Assessment Tool)

  • A computer-based algorithm that calculates a patient's 10-year probability of a major osteoporotic fracture and a hip fracture.
  • It uses clinical risk factors (e.g., age, prior fracture, steroid use) and can also include femoral neck bone mineral density.
  • It is a key tool for assessing a patient's baseline fracture risk.
  • A CHTP uses this to help guide decisions about the use of MHT for osteoporosis prevention.

ASCVD Pooled Cohort Equations Risk Calculator

  • An assessment tool that calculates a patient's 10-year risk of having a first atherosclerotic cardiovascular disease (ASCVD) event.
  • It is used to guide decisions about primary prevention therapies like statins.
  • In the context of hormone therapy, it is used to assess a patient's baseline cardiovascular risk.
  • MHT is generally not recommended for women at high ASCVD risk.
  • A CHTP must be proficient in using this tool.

U.S. Medical Eligibility Criteria for Contraceptive Use (MEC)

  • The CDC's evidence-based guideline for contraceptive safety.
  • It is the most important assessment tool for selecting a safe contraceptive method.
  • It categorizes medical conditions based on the level of risk for each contraceptive method.
  • Category 1: No restriction.
  • Category 2: Advantages generally outweigh the risks.
  • Category 3: Risks generally outweigh the advantages.
  • Category 4: Unacceptable health risk (contraindication).
  • A CHTP must be an expert at using the MEC.

PHQ-9 and GAD-7

  • These are simple, validated screening tools for depression and anxiety.
  • PHQ-9: A 9-item Patient Health Questionnaire for depression.
  • GAD-7: A 7-item Generalized Anxiety Disorder scale.
  • Mood changes are a common symptom of menopause and a potential side effect of hormone therapy.
  • A CHTP can use these tools to screen for and monitor mood symptoms in their patients.

Creatinine Clearance (CrCl) - Cockcroft-Gault

  • Essential for assessing renal function in order to dose adjust medications. While not a hormone itself, many hormone therapy patients are on other medications that require this calculation. It is a fundamental calculation for any clinical pharmacist.

\( \text{CrCl (mL/min)} = \frac{(140 - \text{Age}) \times \text{Weight (kg)}}{72 \times \text{Serum Cr (mg/dL)}} \times (0.85 \text{ if female}) \)

Body Mass Index (BMI)

  • BMI is a critical factor in hormone therapy risk assessment. Obesity is a major risk factor for VTE with estrogen therapy and can affect testosterone dosing.

\( \text{BMI} = \frac{\text{Weight (kg)}}{[\text{Height (m)}]^2} \)

Corrected Calcium for Albumin

  • Since calcium levels are affected by albumin, which can change with age and nutritional status, this calculation is important when assessing bone health. Parathyroid hormone and bone metabolism are closely linked to sex hormones.

\( \text{Corrected Ca} = \text{Serum Ca} + 0.8 \times (4.0 - \text{Serum Albumin}) \)

Ideal Body Weight (IBW)

  • IBW is used in some dosing calculations. While less common for hormone therapy itself, it is a foundational clinical pharmacy calculation that a CHTP should know.

Male: \( 50\text{kg} + 2.3\text{kg for each inch > 5ft} \)
Female: \( 45.5\text{kg} + 2.3\text{kg for each inch > 5ft} \)

Absolute Risk vs. Relative Risk

  • This is a conceptual calculation essential for counseling. For example, if a risk goes from 1 in 10,000 to 2 in 10,000, the relative risk has doubled (100% increase), but the absolute risk increase is only 1 in 10,000. A CHTP must be able to calculate and explain this difference.

Individualization is Everything

  • There is no "one-size-fits-all" approach to hormone therapy.
  • Every decision must be individualized based on the patient's specific symptoms, goals, preferences, and benefit-risk profile.
  • Guidelines provide the framework, but the art of hormone therapy is in the application of these guidelines to the individual.
  • A CHTP is an expert in this patient-centered, individualized approach.

The Benefit-Risk Profile is Dynamic

  • The benefit-risk balance of hormone therapy is not a one-time calculation; it changes over a person's life.
  • A treatment that is appropriate for a newly menopausal 52-year-old may not be appropriate for a 68-year-old.
  • This requires an ongoing, annual reassessment of the need for continued therapy.
  • The CHTP is a leader in this process of continuous re-evaluation.

Shared Decision-Making is the Standard of Care

  • The decision to use hormone therapy is a preference-sensitive one.
  • The role of the clinician is not to tell the patient what to do, but to provide them with the evidence they need to make an informed choice that is right for them.
  • This requires excellent communication skills and a commitment to patient partnership.
  • A CHTP is an expert facilitator of these shared decision-making conversations.

Lowest Dose, Shortest Duration is a Guiding Principle, Not a Dogma

  • The principle of using the lowest effective dose for the shortest duration is a key safety concept, especially for MHT.
  • However, this must be balanced with the patient's individual treatment goals.
  • For some women with persistent symptoms, a longer duration of therapy may be appropriate after a thorough benefit-risk discussion.
  • The CHTP understands the nuance behind this principle.

Stay Current, The Evidence is Always Evolving

  • Hormone therapy is one of the most rapidly evolving and controversial areas in medicine.
  • New evidence from clinical trials is constantly emerging.
  • Professional society guidelines are updated regularly.
  • A CHTP must be a lifelong learner with a commitment to staying at the forefront of the evidence.
  • This is essential for providing the highest quality of care to patients.
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