What it is:Two topics bundled under one course module because they share the same underlying biology: conditions tied to organs found in AMAB (assigned-male-at-birth) anatomy (erectile dysfunction, androgenic alopecia, hypogonadism, BPH, prostate cancer), and gender-affirming hormone therapy (GAHT) for transgender and gender-diverse patients.
The core problem:Almost everything here runs through one axis and one hormone: the hypothalamic-pituitary-gonadal (HPG) axis, and testosterone. Raise it, lower it, block its conversion to DHT, block its conversion to estrogen, or block the receptor entirely, and you've covered nearly every drug class in this document.
What you do about it:For the men's health conditions, identify where in that axis (or which downstream enzyme: 5-alpha reductase, aromatase, PDE-5) the drug intervenes, and the whole treatment ladder becomes logical instead of memorized. For GAHT, remember that nothing is FDA-approved for gender incongruence, everything is guideline-driven and individualized, and the graded skill being tested is a respectful risk-versus-benefit conversation, not a single "correct" dose.
GnRH (hypothalamus) → LH & FSH (pituitary) → testosterone (testes) → two fates: 5-alpha reductaseconverts it to DHT (drives prostate growth, facial/body hair, androgenic alopecia), or aromataseconverts it to estrogen (why "just testosterone" can still feed an estrogen-sensitive cancer, and why excess T given for GAHT can paradoxically cause estrogenic side effects). Testosterone also feeds back to suppress GnRH; LH and FSH suppress themselves through inhibin B. Every drug class below nudges one arrow on this diagram.
These aren't optional vocabulary. Lecture questions are written to distinguish this content from the men's health lecture by using these terms deliberately, so get comfortable with them.
| Term | Meaning |
|---|---|
| Sexvs gender | Sex = biology (organ inventory, chromosomes). Gender = behavioral, cultural, and psychological identity. They're independent variables. |
| Cisgender | Gender identity matches sex assigned at birth. |
| Transgender | Gender identity differs from sex assigned at birth. |
| Gender nonbinary | Gender identity that doesn't fit the male/female binary; a spectrum, an umbrella term. |
| AFAB / AMAB | Assigned Female / Male At Birth. Describes organ inventory, not identity. Expect stems like "a 26-year-old AMAB patient presents for GAHT." |
| Eunuch | New WPATH 2022 term. AMAB, wishes to eliminate masculine features/genitals/function, testes surgically removed or rendered nonfunctional, and self-identifies as eunuch. Does notinclude men treated for prostate cancer who reject that label. |
Gender dysphoriais a DSM-5 mental healthdiagnosis focused on the distress and discomfort of being transgender or gender-diverse (TGD), not on the gender identity itself. Gender incongruenceis an ICD-11 medicaldiagnosis focused on the person's experienced identity and their need for GAHT. You'll see the two used interchangeably in a chart, but pharmacists don't diagnose either one. Think of it like diabetes: a patient whose dysphoria is in remission on stable GAHT is still, medically, incongruent between their body and identity, the same way a well-controlled diabetic is still diabetic even though their A1C looks great.
Guideline landscape you'll see cited throughout: WPATH Standards of Care v8 (2022)is the most widely used and the primary reference for most of this document. UCSF Transgender Care (2016)and Rainbow Health Ontarioare other major guidelines that sometimes disagree on specific numbers. The Endocrine Society 2017 Clinical Practice Guidelineis the source for most monitoring intervals below.
There are no large randomized controlled trials in transgender populations, so guidelines disagree with each other on dosing more than you're used to seeing. Health disparities compound the stakes: the US Transgender Survey found transgender people have dramatically higher rates of living with HIV, suicide attempts, and poverty compared to the general population. The four guiding principles for everyone providing care here: be empowering and inclusive, respect diversity, reduce stigma, and respect bodily autonomy.
Definition:persistent inability to attain or maintain a penile erection sufficient for intercourse. Incidence climbs steeply with age, roughly 52% of men age 40-70. ED is now recognized as an early marker of cardiovascular disease, diabetes, and depression, because all three share the same root problem: endothelial dysfunction and impaired nitric oxide signaling. A 55-year-old with new ED and no other symptoms deserves a cardiovascular workup, not just a prescription.
Sexual stimulation → nitric oxide (NO) release → activates guanylate cyclase → increases cGMP → smooth muscle relaxation in the corpora cavernosa and arterioles → blood flows in, venous outflow drops → erection. Acetylcholine, cAMP, and testosterone (mostly for libido, which gradually declines after age 40) also contribute. PDE-5 normally breaks cGMP back down.Inhibit PDE-5 and cGMP accumulates, so this is a mechanism amplifier, not a stimulant. It needs sexual stimulation to work, which is why "just take the pill" without arousal fails.
| Classification | Common causes | Mechanism |
|---|---|---|
| Neurogenic | Stroke, Alzheimer disease, spinal cord injury, pelvic surgery/injury, DM neuropathy | Interrupted neuronal innervation, failure to trigger NO release |
| Psychogenic | Depression, performance anxiety, relationship stress | Impaired NO release, decreased libido, sympathetic activation |
| Hormonal | Androgen deficiency, hyperprolactinemia, DM, opioid use | Loss of libido, inadequate NO release, penile tissue atrophy |
| Vasculogenic | HTN, atherosclerosis, hyperlipidemia, DM, obesity, trauma | Impaired veno-occlusion, inadequate arterial inflow, endothelial dysfunction |
| Drug-induced | Antihypertensives, antiandrogens, antidepressants, alcohol, smoking | CNS suppression, decreased libido, vascular insufficiency |
| Systemic disease | Aging, DM, chronic renal failure | Multifactorial: neuronal + vascular |
| Class | Examples |
|---|---|
| Diuretics | Thiazides, spironolactone |
| Antihypertensives | CCBs, beta blockers, methyldopa, clonidine, reserpine, guanethidine |
| Cardiac/cholesterol drugs | Digoxin, gemfibrozil, clofibrate |
| Antidepressants | SSRIs, TCAs, lithium, MAOIs |
| Tranquilizers | Butyrophenones, phenothiazines |
| H2 antagonists | Ranitidine, cimetidine |
| Hormones | Progesterone, estrogens, corticosteroids, LHRH antagonists, 5-alpha reductase inhibitors, cyproterone acetate |
| Cytotoxic / immunomodulator | Methotrexate, interferon-alpha |
| Anticholinergics | Disopyramide, anticonvulsants |
| Recreational | Alcohol, cocaine |
Classic exam stem: a patient on an SSRI, a beta blocker, and a stimulant for ADHD develops new ED. Any of the first two could be the culprit; work through the med list systematically rather than assuming.
Non-pharm (vacuum erection device):60-80% effective, fast onset (3-20 min). Downsides: petechiae, may not ejaculate at climax. Use caution with blood thinners or unexplained intermittent priapism. Can be combined with pharmacologic options.
1st line: PDE-5 inhibitors.If partially effective, titrate to the max tolerated dose before switching agents. 2nd line: alprostadil(intracavernosal injection or intraurethral suppository). 3rd line: surgery.
| Agent | Onset | Duration | Dose range |
|---|---|---|---|
| Sildenafil (Viagra) | 30 min | 4 h | 25-100 mg |
| Vardenafil (Levitra) | 30-60 min | 4 h | 5-20 mg |
| Tadalafil (Cialis) | 45 min | 24-36 h | 5-20 mg |
| Avanafil (Stendra) | 30-45 min | 4 h | 50-200 mg |
All four agents have roughly equal response rates (60-80%), lower in patients with prior prostatectomy or diabetes. Tadalafil's 24-36 hour duration is the outlierand the reason it's sometimes dosed daily at low dose instead of on-demand (this is also why it moonlights as a BPH drug, see below). Comparable single doses across agents: sildenafil 50 mg ≈ vardenafil 10 mg ≈ tadalafil 10 mg ≈ avanafil 100 mg, useful when switching a patient who didn't respond well to one agent.
Absolute: nitrates(of any kind), high cardiovascular risk, retinitis pigmentosa, non-arteritic anterior ischemic optic neuropathy history. "High CV risk" specifically means: unstable/refractory angina, uncontrolled HTN, severe CHF (NYHA IV), MI or stroke within 2 weeks, moderate-severe valvular disease, high-risk arrhythmia, or obstructive hypertrophic cardiomyopathy. Warnings:dose-related impaired color discrimination (classic "blue vision" with sildenafil), hearing/vision loss, hypotension, priapism.
Short-acting nitrates require different washout windows after the lastPDE-5i dose: 12 hours after avanafil, 24 hours after sildenafil or vardenafil, 48 hours after tadalafil. Longer half-life drug, longer washout, exactly what you'd predict, but the specific numbers are worth memorizing since they're an easy multiple-choice distractor. Long-acting nitrates should be avoided with PDE-5i altogether. Also watch alpha-blockers(additive orthostatic hypotension risk, this matters a lot in a BPH patient also using sildenafil) and CYP3A4 inhibitorslike grapefruit juice, protease inhibitors, and azole antifungals, which raise PDE-5i levels.
| Option | Notes |
|---|---|
| Alprostadil, intraurethral (MUSE) | 125-1,000 mcg. 40-66% effective. Onset 5-10 min; attempt intercourse within 10-30 min. |
| Alprostadil, intracavernosal (Caverject, Edex) | 2.5-50 mcg via 27-30 gauge needle. 70-90% effective but 30-50% discontinue. Onset 5-15 min, duration ≤1 h. MOA: prostaglandin E1 stimulates adenylyl cyclase → ↑cAMP → smooth muscle relaxation. |
| Papaverine / phentolamine | Adjuncts, often combined with alprostadil. |
| Botulinum neurotoxin | ~40-50% effective, reserved for PDE-5i non-responders. |
| L-arginine (OTC) | Possibly effective. Avoid combining with PDE-5i (additive hypotension). ADEs: dizziness, headache, flushing. |
| Panax ginseng (OTC) | Possibly effective. Increases bleeding risk. |
| Yohimbine (OTC) | Insufficient evidence. GI upset, anxiety, tachycardia, arrhythmias. |
| Eroxon® (topical gel) | FDA approved June 2023. Applied to the glans; ~2x the efficacy of its own placebo formulation in trials. Not a hormone or vasodilator drug, works through a rapid cooling sensation effect. |
Every hair follicle is present at birth and cycles through growth and shedding continuously; normally ~80-90% of follicles are in a growth phase at any time, with ~75 follicles shedding and the same number entering new growth daily. In androgenic alopecia, androgens shorten that growth phase.
DHT binds the androgen receptorin a genetically predisposed follicle → activates genes that shorten the growth (anagen) phase → follicular miniaturization: progressively shorter, thinner hair shafts each cycle. Of the two 5-alpha reductase isoforms in scalp follicles, type 2 plays the larger rolein male-pattern hair loss, which is exactly why a type-2-selective inhibitor works here.
| Drug | MOA | Dose & counseling |
|---|---|---|
| Minoxidil | Increases anagen duration, shortens telogen, enlarges follicles. Topical benefit depends on conversion to active minoxidil sulfate. | 1 mL foam (half capful) or liquid, applied twice daily, targeted at the scalp, not the hair. Early shedding is expected and usually resolves within 2 months; 4 months may be needed to see growth. Benefit is lost if stopped. ADR: contact dermatitis. |
| Finasteride(Propecia) | Competitively inhibits 5-alpha reductase type 2, reducing testosterone-to-DHT conversion. | 1 mg PO once daily. Less sexual dysfunction than the higher doses used for BPH. Continue for 6-12 months minimum, and must be continued to maintain benefit. ADR: dizziness. Teratogenic, avoid handling broken tablets if pregnant. |
Finasteride 1 mg for alopecia is a much lower dosethan the 5 mg used for BPH, which is why sexual dysfunction is less common at the alopecia dose. Don't assume "finasteride" means one fixed dose; the indication determines it.
The HPG axis: GnRH → LH and FSH → LH drives testosterone production; FSH (via inhibin B) drives spermatogenesis.Testosterone feeds back to suppress GnRH; inhibin B feeds back to suppress FSH. Testosterone's downstream effects: facial/body hair and scalp hair loss (skin), sperm production/prostate growth/erectile function (sex organs), muscle mass and strength, sex drive and aggression (brain), red blood cell production (bone marrow), and bone density maintenance.
Both present with low serum testosteroneand/or low sperm count. The difference is what LH/FSH are doing. Primary hypogonadism(testicular disease) → LH/FSH are elevatedbecause the pituitary is trying harder to stimulate a testis that can't respond. Secondary hypogonadism(hypothalamic/pituitary disease) → LH/FSH are normal or lowbecause the signal itself is broken. Both can be congenital or acquired.
Primary (testicular):congenital, Klinefelter syndrome, androgen synthesis disorders, FSH receptor mutation, cryptorchidism, varicocele, myotonic dystrophy; acquired, cirrhosis, chronic renal failure, HIV/AIDS, autoimmune damage, infections (mumps), radiation, trauma, testicular torsion, environmental toxins, idiopathic, medications.
Secondary (hypothalamic/pituitary):congenital, isolated gonadotropin deficiency, Kallmann syndrome, various receptor/gene mutations, Prader-Willi syndrome, panhypopituitarism; acquired, hyperprolactinemia, critical or chronic systemic illness, diabetes, pituitary tumors/cysts, infiltrative disease (sarcoidosis, hemochromatosis), infection (meningitis), pituitary apoplexy, trauma, surgery/radiation to the sellar region, medications.
Primary:corticosteroids, ethanol, ketoconazole, finasteride, spironolactone, flutamide, cimetidine. Secondary:corticosteroids, anabolic steroids, opioids, ethanol, marijuana, GnRH analogs, estrogen, progestins, metoclopramide. Note corticosteroids and ethanol appear on both lists, they hit the axis at multiple levels.
Testosterone falls ~0.4-2% per year after age 30. By the 7th decade, 35% of men have lower testosterone than younger men, but only 13%actually meet diagnostic criteria for hypogonadism. Symptoms of low T overlap heavily with normal aging, which is exactly why diagnosis requires both a lab abnormality and a symptom picture, not either alone.
| Nonspecific | Suggestive | Specific |
|---|---|---|
| ↓ energy, motivation, confidence; low mood; poor concentration/memory; sleep disturbance; mild normocytic anemia; ↓ muscle bulk; ↑ body fat/BMI | ↓ sexual desire; fewer spontaneous erections/ED; gynecomastia; eunuchoidal body proportions; infertility/low sperm count; height loss, low-trauma fracture, low BMD; hot flushes | Incomplete/delayed sexual development; loss of axillary/pubic hair; very small testes (<6 mL) |
Total testosterone (free plus protein-bound) normal range: 300-1,100 ng/dL. Testosterone has strong diurnal fluctuation, peaking around 8 AM and troughing around 8 PM, and food lowers serum levels, so the sample must be drawn fasting, in the morning. Treat only when both a distinctly subnormal testosterone leveland consistent clinical signs/symptomsare present, not either alone.
Recommend against testosterone replacement if the patient: is planning near-term fertility; has breast or prostate cancer, a palpable prostate nodule, or induration; has PSA >4 ng/mL (or >3 ng/mL combined with high prostate cancer risk without urology evaluation); has elevated hematocrit; has untreated severe OSA; has severe lower urinary tract symptoms; has uncontrolled heart failure; had an MI or stroke in the last 6 months; or has thrombophilia.
The prostate's job is contributing seminal fluid. Its development and maintenance are androgen-dependent: testosterone is converted by 5-alpha reductaseto DHT, which drives both normal and hyperplastic overgrowth of stromal and epithelial cells. That enlargement contributes to lower urinary tract symptoms (LUTS). BPH prevalence rises sharply with age: 8% in the 4th decade, 50% in the 5th, 80% by the 9th.
Seven questions, each scored 0-5 (incomplete emptying, frequency <2h, intermittency, urgency, weak stream, straining, nocturia), for a total of 0-35, plus a separate quality-of-life question.
| Score | Severity |
|---|---|
| 0-7 | Mild |
| 8-19 | Moderate |
| ≥20 | Severe |
| Class | MOA / role |
|---|---|
| Alpha-1 blockers | 1st line. Relax smooth muscle in the prostate and bladder neck. Fast symptom relief, doesn't shrink the gland. |
| 5-alpha reductase inhibitors | Block testosterone-to-DHT conversion. Only useful with actual prostate enlargement, not for pure LUTS without enlargement. |
| PDE-5 inhibitor (tadalafil) | MOA in BPH not fully defined; relaxes detrusor and prostatic smooth muscle. |
| Anticholinergics / beta-3 agonists | Target overactive bladder component by relaxing detrusor smooth muscle. |
Nonselectivealpha-1 blockers (terazosin, doxazosin) also hit alpha-1B and alpha-1D receptors in the heart and arteries, so they cause more orthostasis, dizziness, and headache, and both require slow bedtime-dosed titration schedules for exactly that reason. Selectivealpha-1A blockers (tamsulosin, alfuzosin, silodosin) target the prostate specifically with far less cardiovascular side effect burden. That selectivity is also why tamsulosin/alfuzosin/silodosin carry the bigger intraoperative floppy iris syndrome (IFIS)risk during cataract surgery, since alpha-1A receptors are also on the iris dilator muscle. Delay starting an alpha blocker until after planned cataract surgery.
Finasterideselectively, competitively inhibits the type 2isozyme. Dutasterideis nonselective, inhibiting both type 1 and type 2. PSA serves as a proxy for prostate volume when deciding who benefits: a gland with PSA below 1.5 ng/mLis likely too small to benefit, while volumes above 35 gare where the literature supports real benefit. These drugs reduce prostatic volume and prevent progression, but max symptom relief takes 6-12 months, so they are not for acute symptom control. Side effects: sexual dysfunction (ED, decreased libido, ejaculatory dysfunction), gynecomastia/breast tenderness, and potential fetal harm if handled by a pregnant person.
Important interpretation trap:5-ARIs lower PSA. A patient on finasteride or dutasteride with a "normal" PSA may actually be masking an elevated one; some guidelines suggest doubling the measured value for interpretation purposes when screening for prostate cancer in these patients.
Anticholinergicsare reserved for when overactive bladder symptoms predominate. Extended-release formulations are generally better tolerated. Side effects: urinary retention, dry mouth, blurred vision, tachycardia, drowsiness, reduced gut motility; avoid if post-void residual (PVR) >250-300 mLsince retention risk compounds; there's an associated dementia risk signal with long-term anticholinergic burden. Darifenacin and solifenacinare selective for M3 receptors; trospiumhas limited blood-brain-barrier penetration, making it a reasonable pick in older adults.
Beta-3 agonists: mirabegronis a moderate CYP2D6 inhibitor and can raise BP/HR (arthralgia, abdominal pain, fatigue also reported); vibegronhas less effect on BP/HR (headache, diarrhea, constipation, nausea instead). The 2023 AUA guideline only supports beta-3 agonists in combination with an alpha blocker, not as monotherapy for BPH.
| Alpha blockers, selective | ||
| Tamsulosin (Flomax) | 0.4 mg once daily, ~30 min after a meal | May increase to 0.8 mg after 2-4 wk if inadequate response |
| Alfuzosin (Uroxatral) | 10 mg once daily, immediately after a meal | Fixed dose |
| Silodosin (Rapaflo) | 8 mg once daily with a meal | Fixed dose |
| Alpha blockers, nonselective (bedtime titration required) | ||
| Doxazosin IR (Cardura) | 1 mg qHS days 1-3 | → 2 mg (d4-14) → 4 mg (wk2-6) → 8 mg (wk7+) |
| Terazosin (Hytrin) | 1 mg qHS days 1-3 | → 2 mg (d4-14) → 5 mg (wk2-6) → 10 mg (wk7+), max 20 mg if inadequate at wk4-6 of 10 mg |
| 5-alpha reductase inhibitors | ||
| Finasteride (Proscar) | 5 mg daily | No titration |
| Dutasteride (Avodart) | 0.5 mg daily | No titration |
| PDE-5 inhibitor | ||
| Tadalafil | 5 mg daily | No titration |
| Beta-3 agonists | ||
| Mirabegron (Myrbetriq) | 25 mg daily | May increase to 50 mg after ≥4 wk |
| Vibegron (Gemtesa) | 75 mg daily | No titration |
The AUA guidelines do not recommend natural products for BPH symptoms. Saw palmetto, stinging nettle, African cherry (pygeum), zinc, and selenium are all considered unlikely to be effective.
Oncology dosing/staging is covered elsewhere in the curriculum; this section is scoped to the hormonal agents you're expected to know.
PSA can rise from cancer, but also from prostate infection, enlargement, or recent prostate procedures, and 5-ARIs artificially lower it.Five-year survival by stage: Stage I 90-95%, Stage II 60-70%, Stage III 30-40%, Stage IV 20%, underscoring why early detection matters.
Not a surgical/radiation candidate; disease persists or returns after radiation/surgery; combined with radiation upfront for high-risk disease; or neoadjuvant to shrink the tumor before radiation.
| Approach | Agents |
|---|---|
| Surgical castration | Orchiectomy |
| Chemical castration, GnRH agonist(+ antiandrogen) | Leuprolide (Lupron, Eligard, Camcevi), goserelin (Zoladex), triptorelin (Trelstar), histrelin (Vantas) |
| Chemical castration, GnRH antagonist | Degarelix (Firmagon), relugolix (Orgovyx) |
GnRH agonistsinitially cause a surge of LH/FSH release, meaning an initial risein testosterone, before receptors downregulate after about a week and testosterone falls to castrate levels over 3-4 weeks. That transient flare is exactly why agonists are paired with an antiandrogenat initiation, otherwise the flare can worsen bone pain or cause spinal cord compression in patients with metastatic disease. GnRH antagonistsbind the receptor without stimulating LH/FSH release at all, so there's no flareand castrate testosterone levels are reached faster.
Sexual dysfunction, bone fractures/osteoporosis, cardiovascular disease and diabetes risk, reduced muscle mass with increased fat, cognitive dysfunction, hot flashes, gynecomastia, reduced energy, depression.
Bone protection bundle:weight-bearing exercise, reduced alcohol intake, smoking cessation, calcium 1,000-1,200 mg/day, vitamin D 800-1,000 IU/day, and an osteoclast inhibitor (e.g. a bisphosphonate) if T-score <-2.5 or FRAX >3% hip fracture risk (or >20% major osteoporotic fracture risk).
| Generation | Agents |
|---|---|
| 1st generation | Flutamide (Eulexin), bicalutamide (Casodex), nilutamide (Nilandron) |
| 2nd generation | Enzalutamide (Xtandi), apalutamide (Erleada), darolutamide (Nubeqa) |
For castration-resistant prostate cancer (CRPC), alternative endocrine approaches include abiraterone(androgen biosynthesis inhibitor, must be taken with prednisone; SEs myalgias, elevated BP, fluid retention, hot flashes, GI upset/diarrhea) and enzalutamide(androgen receptor inhibitor, used concurrently with a GnRH agonist; SEs fatigue, diarrhea, hot flashes, musculoskeletal pain, headache, and rare seizures). Older alternative approaches: ketoconazole, glucocorticoids, megestrol acetate, and estrogens.
This used to be called "feminizing hormone therapy." The term has shifted because hormones aren't inherently gendered: cisgender men have circulating estrogen, cisgender women have circulating testosterone. No medication used for GAHT is FDA-approved for gender incongruence, everything here is guideline-driven, off-label prescribing. The standard starting and continuing regimen is an antiandrogen plus estrogen.
Development of female secondary sex characteristics and suppression of male ones: breast development, redistribution of subcutaneous fat and muscle mass, reduced body hair, change in sweat/odor patterns, and arrest of scalp hair loss (a nice secondary benefit if androgenic alopecia is present).
Age (an escalating-risk discussion looks very different in a 20-year-old vs. a 74-year-old with diabetes and heart disease), smoking status (raises clot risk), migraine with or without aura, uncontrolled BP or diabetes, and personal/family history of breast, uterine, or ovarian cancer, stroke, or DVT/VTE.
Unlike combined hormonal contraceptives, migraine with aura is notan absolute contraindication to estrogen-centered GAHT. It does raise clot/stroke risk on top of the estrogen risk, so it demands a real risk-versus-benefit conversation, but for most transgender patients the benefit outweighs that added risk. Don't reflexively apply the combined-OCP rule here.
| Agent | Use in GAHT |
|---|---|
| 17-beta estradiol | Used. Bioidentical to estrogen from the human ovary. |
| Conjugated equine estrogens | Not used, higher clot and cardiovascular risk. |
| Ethinyl estradiol | Not used, this is the contraceptive estrogen and carries a higher clot risk. |
Formulations of 17-beta estradiol include oral tablets (often taken sublingually off-label, dissolved under the tongue, even though no sublingual product exists, specifically to bypass first-pass hepatic metabolism and lower clot risk), transdermal patches/gels (theoretically the lowest clot risk), and IM/SC injectable esters (valerate, cypionate).
Can be used alone (to reduce masculinization with minimal breast development, to "test the waters" with lower circulating testosterone, or when estrogen itself is contraindicated) or combined with estrogen, which allows lower estrogen doses.
| Agent | Details |
|---|---|
| Spironolactone("spiro") | Most common. Potassium-sparing diuretic that directly inhibits testosterone synthesis at higher doses and binds androgen receptors on the testes/adrenal glands. 100-400 mg/day, notably higher than typical HF/HTN dosing. Monitor potassium, BP, hot flashes, low mood/energy. |
| 5-ARIs (finasteride, dutasteride) | Alternative if spironolactone is intolerable (e.g. sulfa allergy) or a "two-for-one" if alopecia is also present. No added benefit once already at goal on spiro + estradiol. |
| Cyproterone acetate | Synthetic progestin with strong antiandrogen activity. International use only, not in the US, due to fulminant hepatitis risk. |
| Bicalutamide | Direct antiandrogen (also used in prostate cancer). Small but quantified risk of LFT abnormalities/fulminant hepatitis. |
| GnRH analogs (leuprolide) | Effective but usually not insurance-covered and requires repeat injections. Reserved for refractory cases or patients not pursuing orchiectomy. |
This is a hot-button, patient-driven topic. The Women's Health Initiativefound increased cardiovascular disease and breast cancer risk specifically with medroxyprogesterone acetatein cisgender women. Extrapolating that to GAHT: WPATHcalls the evidence insufficient, noting increased CVD risk/mortality appears minimal-to-absent compared to WHI; UCSFflags a theoretical direct androgenizing effect; an Endocrine Journalreview found no evidence progesterone enhances breast development in transgender patients, but also no evidence it doesn't.
Bottom line:current guidelines have largely walked back routinely recommending it, but it's low risk, and patients often ask for it based on community anecdote (Reddit, peer reports of perceived benefit). The right pharmacist response is neither a flat "it's not indicated, don't" nor an enthusiastic "sure, it's basically free benefit," it's a risk-versus-benefit conversation with the prescriber.
| WPATH | UCSF | Rainbow Health Ontario | |
|---|---|---|---|
| Estradiol, oral/SL | 2-6 mg/day | 2-4 mg/day, max 8 mg | 1-2 mg, max 6 mg |
| Estradiol, topical gel | 25-200 mcg | 100 mcg, max 400 mcg | 50 mcg, max 200 mcg |
| Estradiol valerate IM | 5-30 mg q2wk | Initial 2-4 mg/wk, max 20 mg/wk | Initial 8 mg q2wk, max 10 mg/wk |
| Estradiol cypionate IM | 2-10 mg/wk | Initial 1-2 mg/wk, max 5 mg/wk | - |
| Spironolactone | 100-300 mg/day | 50 mg BID, max 200 mg BID | 100 mg BID, max 150 mg BID |
| Cyproterone acetate | 10 mg/day | - | 25 mg, max 50 mg daily |
| GnRH agonist | 3.75 mg SQ/IM, max 7.5 mg | - | - |
Progestin dosing (UCSF): medroxyprogesterone acetate initial-low 2.5 mg qHS, max 5-10 mg qHS. Micronized progesterone max 100-200 mg qHS (dosed at bedtime because it's sedating; it's suspended in peanut oil, so screen for peanut allergy before recommending it).
| Tier | Risks |
|---|---|
| Increased risk | VTE, infertility, hyperkalemia, weight gain, hypertriglyceridemia |
| Likely increased | Cardiovascular disease, cholelithiasis |
| Increased with risk factors | Hypertension, erectile dysfunction |
| Possible increased risk | Type 2 diabetes, low bone mineral density, hyperprolactinemia |
| Possible, with added risk factors | Breast or prostate cancer |
Never use ethinyl estradiol. Prefer topical, patch, or sublingual routes over oral tablets to avoid first-pass metabolism. Never exceed the upper limit of normal estrogen for a cisgender woman.
Timeline of effects:most changes unfold over months to years; effects plateau at roughly the 5-year mark, after which further physical change from hormones alone is unlikely and anything beyond that ceiling requires surgery. Fat redistribution, muscle loss, and mood are more reversible if therapy stops; breast development is not.
Goals:facial hair development, voice deepening, redistribution of facial/body fat, temporal hairline recession, and cessation of menses. No added antiandrogen is typically needed on this side, testosterone alone drives the transition.
Pregnancy or breastfeeding, smoking (risk-raiser, not absolute), active hormone-sensitive cancer, unstable ischemic cardiovascular disease, uncontrolled hypertension/diabetes/dyslipidemia, history of VTE or a hypercoagulable state (e.g. antiphospholipid syndrome).
Testosterone often suppresses the menstrual cycle, but it is not reliable contraception; ovulation can still occur intermittently. Always have the fertility-preservation conversation before starting, since return of fertility after prolonged suppression isn't guaranteed. Avoid combined estrogen-containing methods (works against masculinization goals, and even a NuvaRing delivers meaningful systemic estrogen); a progestin-only pill, copper IUD, or levonorgestrel IUDare more compatible choices. Always recommend a backup method even if the patient is amenorrheic on testosterone.
| Formulation | Notes |
|---|---|
| IM/SC cypionate or enanthate | Weekly to every-2-week dosing across guidelines, roughly 50-100 mg/wk or 100-200 mg q2wk. Controlled substance. |
| IM undecanoate | Dosed roughly every 10-12 weeks. Must be administered in a healthcare setting under a REMS program; know it exists, you are not the one monitoring it. |
| Topical gel (1%, 1.62%, 2%) | Common starting formulation. Strength and mg-per-application vary by product, check the specific concentration before counseling. |
| Transdermal patch | Not available since 2023, a discontinued option you may still see referenced in older guideline tables. |
Two needles are typical: an 18-gaugeto draw up (bigger lumen, smaller gauge number), and a 21-23 gauge, 1-1.5 inchneedle to inject IM. Two alcohol swabs (one for the vial, one for the skin), a syringe sized to the dose (1 mL syringes are easier to read accurately for sub-1-mL doses than 3 mL syringes), and a sharps container. Most supplies can be dispensed without a prescription, but confirm your organization's policy.
Apply in the morningfor gradual release through the day, to the upper arms or shoulders only, and let it stay dry at least 2 hoursbefore any skin-skin contact. Gel residue transfers via clothing and skin contact, and there are documented cases of secondhand exposure causing virilization in children (clitoral enlargement in infant girls from contact with a parent's application site). Counsel patients to wash the site before expected close contact, especially with women or children.
Mood swings, hair loss, acne; increased risk of metabolic syndrome and related conditions (PCOS, hyperlipidemia, impaired glucose tolerance).
Testosterone is contraindicated in active hormone-sensitive cancer, including estrogen-positive breast cancer, because excess testosterone is aromatized to estrogen.Patients (and easily, students) assume testosterone can't matter for an estrogen-driven tumor. It can. This is also the mechanism behind the counseling point that more testosterone isn't automatically better: past a certain dose, the excess gets converted to estrogen and can produce effects opposite of what the patient wants.
Vaginal drynesscan be managed with low-dose vaginal estrogen (doesn't reach meaningful systemic levels) or OTC moisturizers if the patient prefers to avoid any estrogen product.
| Tier | Risks |
|---|---|
| Likely increased | Polycythemia, infertility(the two flagged as most clinically significant), acne, androgenic alopecia, hypertension, sleep apnea, weight gain, ↓HDL/↑LDL |
| Likely increased, with risk factors | Cardiovascular disease, hypertriglyceridemia |
| Possible, with risk factors | Type 2 diabetes, cardiovascular disease |
| No increased or inconclusive risk | Low bone mass/osteoporosis, breast/cervical/ovarian/uterine cancer |
Dosing philosophy: individual response can't be predicted from genetics alone, so start low and titrate to desired effectrather than front-loading a high dose.
Nonbinary describes gender that doesn't fit strictly male or female, an umbrella spectrum term. Nonbinary patients may want a partial or androgynous outcome rather than a full binary transition, and that changes the counseling.
If hormone therapy stops and gonads are retained, most changes revert toward baseline. But some changes are permanent regardless of binary or nonbinary goals: male-pattern baldness progression, genital growth, and facial hair growth in AFAB patients; breast development in AMAB patients. Always have the fertility preservation conversation up front, since anything sustained long enough tends to stick.
Definition: AMAB, wishes to eliminate masculine physical features, genitals, or genital function; testes surgically removed or rendered nonfunctional by chemical or physical means; and self-identifies as eunuch. This explicitly excludesmen treated for advanced prostate cancer who reject the eunuch label. Options: medical (hormone therapy) and/or surgical (orchiectomy). Recommend a minimum of 6 monthsof hormone therapy before pursuing irreversible surgery, unless hormones are medically contraindicated. Most common medical approach: antiandrogens (cyproterone acetate, not US-available, or spironolactone) or estrogen; GnRH analogs are used less often due to cost. Continue sexuality education and counseling, don't assume loss of desire for sexual functioning just because genital functioning is being eliminated.
Per WPATH, all of the following must be met before initiating hormonal care: gender incongruence that is marked and sustained over time; emotional and cognitive maturity sufficient for informed consent; education on mental health and reproductive effects, including fertility preservation options; and at minimum, Tanner stage 2 of puberty.Generally at least 12 months of GAHTis required before any gender-affirming surgery, unless hormone therapy is not desired or is medically contraindicated.
| Timing | Approach |
|---|---|
| Before Tanner stage 2 | Non-pharmacologic only: consultation/psychotherapy, ongoing education and support, social affirmation (chosen name, clothing, hairstyle). No medications, regardless of parental request. |
| After Tanner stage 2, fully reversible | GnRH analogs (histrelin, leuprorelin, nafarelin) pause puberty. AFAB: stops estrogen/progesterone production (alt: continuous progestin or OCP). AMAB: stops LH secretion → stops testosterone (alt: progestin + androgen blocker). Spontaneous puberty resumes if discontinued. |
| Partially reversible | Cross-sex hormone medications (estrogen or testosterone) once a transition decision is made. |
| Completely irreversible | Surgery. Outside pharmacist scope, mentioned for context only. |
Puberty must have started(confirming the HPG axis is actually active) but not yet progressed to irreversible secondary sex characteristics. Suppressing at that exact window preserves time to decide while remaining fully reversible. Starting earlier, before any pubertal onset, isn't the recommended pathway, non-pharmacologic support is the answer for a prepubertal child regardless of how strongly the family is requesting medication.
Introducing female puberty:oral estradiol start 5 mcg/kg/day, increase by 5 mcg/kg/day every 6 months up to 20 mcg/kg/day until post-pubertal, then titrate to adult dosing (2-6 mg/day). Transdermal estradiol start 6.25-12.5 mcg/24h (patches must be cut to achieve this dose), increase by 12.5 mcg/24h every 6 months to adult dosing (50-200 mcg/24h).
Inducing male puberty:testosterone esters start 25 mg/m² every 2 weeks, increase by 25 mg/m² every 2 weeks, reassessed every 6 months until adult dosing and target testosterone levels (400-700 ng/dL) are achieved.
Jurisdiction-specific note (Oregon):the age of medical consent is 15, meaning an adolescent can obtain GAHT at a clinic without parental consent, while the age of sexual consent is 18. Those are two separate, unrelated thresholds, and the gap between them is a real source of awkward pharmacy-counter moments when a parent picks up a prescription for a minor without knowing what it's for.
| Regimen | When | Watching for |
|---|---|---|
| Cisgender male TRT | Initiation/dose changes q2-3mo; stable dose q6-12mo. Gel: 2 measurements before adjusting dose. Transdermal: peak 6-8h post-patch. Injections: measure midway between doses. | Target mid-normal range, 400-700 ng/dL. Stop TRT if hematocrit ≥54%.Consider discontinuing after 6-12 months if testosterone normalizes but symptoms don't improve. |
| GAHT, estrogen-based | q3 months for the first year, then 1-2x/year (Endocrine Society 2017) | Serum testosterone <50 ng/dL; serum estradiol not to exceed 100-200 pg/mL. Spironolactone: potassium q3mo x1 year, then annually. |
| GAHT, testosterone-based | q3 months for the first year for virilization/AEs; total T q3mo until mid-male range achieved | Total T 400-700 ng/dL; Hgb/Hct q3mo x1yr then 1-2x/yr (erythropoietic risk); clinical response = amenorrhea by 6 months; estradiol suppressed <50 pg/mL. |
| 5-ARI for BPH | Baseline PSA, periodic thereafter | PSA is artificially lowered; interpret trends knowing that, and remember max symptom benefit takes 6-12 months. |
| ADT for prostate cancer | Baseline and periodic | Bone density (T-score, FRAX), lipids, glucose, mood/cognitive changes. |
| Any retained-organ screening | Ongoing per organ inventory | Trans women retain the prostate (continue routine prostate cancer screening); trans men with a retained cervix need pap smears; retained breast tissue needs mammograms per usual guidelines regardless of hormone regimen. |
Reference ranges are sex-based, not identity-based, in most EMRs, which causes real confusion. A trans woman adequately suppressed on estrogen-based therapy will often show hemoglobin/hematocrit in the femalerange, and an EMR still flagged male may read that as anemia when it's actually expected, adequately suppressed physiology. A trans man no longer menstruating should trend toward the male Hgb/Hct range, since he's no longer losing blood monthly; if his labs are still reading low, that's worth investigating.