Hormonal therapies encompass drugs that replace, block, or modulate the effects of endogenous hormones. They are essential in endocrinology, reproductive health, and oncology.
Thyroid Medications
Thyroid Hormone Replacement
Levothyroxine (T4) is the standard treatment for hypothyroidism. It is a synthetic form of thyroxine that is converted to the active hormone triiodothyronine (T3) in peripheral tissues. The typical dose is 1.6 mcg/kg/day (50-200 mcg daily). Levothyroxine should be taken on an empty stomach (30-60 minutes before breakfast) with water, and at least 4 hours apart from calcium, iron, magnesium supplements, and antacids. TSH is monitored 6-8 weeks after dose changes (target TSH 0.5-2.5 mIU/L for most patients). Starting dose is lower in older adults and those with CAD. Overtreatment (suppressed TSH) causes iatrogenic hyperthyroidism (palpitations, anxiety, bone loss). Undertreatment (elevated TSH) leaves hypothyroid symptoms unresolved.
Antithyroid Drugs
Methimazole is the first-line antithyroid drug for hyperthyroidism (Graves disease, toxic nodular goiter). It inhibits thyroid peroxidase, reducing thyroid hormone synthesis. Propylthiouracil (PTU) is second-line (reserved for first trimester of pregnancy, thyrotoxic crisis, or methimazole allergy). Side effects include agranulocytosis (0.3-0.5%) — requires monitoring for fever and sore throat — and hepatotoxicity (PTU carries a black box warning for severe liver injury). Beta-blockers (propranolol) are used for symptom control (tachycardia, tremor, anxiety) until antithyroid drugs take effect (2-4 weeks for symptom improvement, 4-8 weeks for euthyroid state).
Corticosteroids
Glucocorticoids
Glucocorticoids have powerful anti-inflammatory and immunosuppressive effects. They bind to the glucocorticoid receptor, regulating gene transcription. Prednisone (5-60 mg/day) and prednisolone are the most commonly used oral glucocorticoids. Hydrocortisone is the physiologic replacement for adrenal insufficiency (15-25 mg/day divided). Dexamethasone is a long-acting glucocorticoid with no mineralocorticoid activity, used for high-dose pulse therapy (cerebral edema, severe COVID, septic shock) and as a diagnostic test for Cushing syndrome.
Potency equivalencies: hydrocortisone 20 mg = prednisone 5 mg = methylprednisolone 4 mg = dexamethasone 0.75 mg.
Short-term adverse effects include hyperglycemia, hypertension, fluid retention, mood changes (euphoria to depression to psychosis), insomnia, and increased appetite. Long-term adverse effects include Cushing syndrome (moon face, buffalo hump, central obesity, striae), osteoporosis (bone loss of 5-15% per year with chronic use — require calcium, vitamin D, and often bisphosphonate therapy), adrenal suppression (HPA axis suppression — requires slow taper to allow recovery; stress-dose coverage needed for illness, injury, or surgery), impaired wound healing, increased infection risk, cataracts (posterior subcapsular), glaucoma, myopathy (proximal muscle weakness), and growth suppression in children.
Mineralocorticoids
Fludrocortisone is a synthetic mineralocorticoid used in primary adrenal insufficiency (Addison disease) and salt-wasting congenital adrenal hyperplasia. It promotes sodium retention and potassium excretion in the kidney. Dosing is 0.05-0.2 mg daily.
Diabetes Medications
Insulin
Insulin is required for type 1 diabetes and advanced type 2 diabetes. Types: rapid-acting (lispro, aspart, glulisine — onset 10-30 min, peak 1-2 hours, duration 3-5 hours), short-acting (regular insulin — onset 30 min, peak 2-4 hours, duration 5-8 hours), intermediate-acting (NPH — onset 1-2 hours, peak 4-8 hours, duration 12-16 hours), and long-acting (glargine, detemir, degludec — onset 1-2 hours, no pronounced peak, duration 20-42 hours). Inhaled insulin (Afrezza) is a rapid-acting alternative.
Common insulin regimens include basal-bolus (long-acting once daily + rapid-acting before meals — mimics physiologic insulin, common in type 1 and intensive type 2 management), and mixed split (NPH + regular twice daily — simpler but less flexible). The main adverse effect is hypoglycemia (can be severe — sweating, palpitations, confusion, seizure, loss of consciousness). Weight gain occurs with improved glycemic control.
Non-Insulin Diabetes Drugs
Metformin is first-line for type 2 diabetes. It reduces hepatic glucose production, improves insulin sensitivity, and does not cause hypoglycemia. It is weight-neutral or causes modest weight loss. GI side effects (diarrhea, nausea — 20-30% initially, usually improves with dose titration and Extended Release formulation). Contraindicated in severe renal impairment (GFR under 30 mL/min) — risk of lactic acidosis (rare, 3-10 cases per 100,000 patient-years).
SGLT2 inhibitors (empagliflozin, dapagliflozin, canagliflozin) reduce glucose reabsorption in the kidney, lowering blood glucose independent of insulin. They have cardiovascular and renal benefits (reduce HF hospitalizations by 30-35%, slow CKD progression). Side effects: genitourinary infections, volume depletion, diabetic ketoacidosis (euglycemic DKA — can occur with normal glucose levels).
GLP-1 receptor agonists (semaglutide, liraglutide, dulaglutide, tirzepatide) slow gastric emptying, increase insulin secretion, and suppress appetite. They produce significant weight loss (5-15% of body weight). They have cardiovascular benefits (reduce MACE by 10-15%). GI side effects are common (nausea, vomiting, delayed gastric emptying). They carry a black box warning for medullary thyroid carcinoma (rare, based on rodent data). Pramlintide, DPP-4 inhibitors (sitagliptin), sulfonylureas (glipizide, glyburide), and TZDs (pioglitazone) are additional options.
Sex Hormones
Estrogens and progestins are used for hormone replacement therapy (menopause), contraception (combined oral contraceptives, patches, rings), and menstrual disorders. Combined hormonal contraceptives increase the risk of venous thromboembolism (3-4 fold), especially in smokers over 35. Testosterone replacement is covered in the Men’s Health section. Anabolic steroids are Schedule III controlled substances with abuse potential, used illicitly for performance enhancement.
Summary
Hormonal therapies include thyroid medications (levothyroxine for hypothyroidism, methimazole for hyperthyroidism), glucocorticoids (potent anti-inflammatory with significant long-term toxicity requiring slow taper), diabetes medications (insulin for all type 1 and advanced type 2; metformin/SGLT2i/GLP-1 RA for type 2), and sex hormones (contraceptives, HRT, androgens). Each class has specific indications, monitoring requirements, and side effect profiles.