Hormonal Therapies: Endocrine Pharmacology, Hormone Replacement, Contraceptives, and Endocrine Modulators

Introduction

Hormonal therapies encompass drugs that mimic, block, or modify the action of endogenous hormones. These agents are used across endocrinology, reproductive medicine, oncology, and inflammatory diseases. Hormonal pharmacology requires understanding feedback loops, receptor mechanisms, and the complex interplay of the endocrine system.

Thyroid Hormones and Antithyroid Drugs

Thyroid Hormone Replacement

Drug	Composition	Onset	Half-Life	Equivalent Dose	Indications
Levothyroxine (T4)	Synthetic T4 (tetraiodothyronine)	3-5 days (full effect 6-8 weeks)	7 days	100 mcg = 1 grain desiccated thyroid	Primary hypothyroidism, myxedema coma, TSH suppression (thyroid cancer)
Liothyronine (T3)	Synthetic T3 (triiodothyronine)	1-3 hours	1 day	25-50 mcg T3 = 100 mcg T4	Severe hypothyroidism (myxedema coma), short-term TSH suppression
Desiccated thyroid	Natural porcine T4/T3 (ratio ~4:1)	Variable	Variable	60-120 mg	Alternative therapy, controversial

Dosing and Monitoring

Parameter	Target (Primary Hypothyroidism)	Target (Thyroid Cancer Suppression)
TSH	0.5-2.5 mIU/L	Low (0.1-0.5 mIU/L for intermediate risk; <0.1 mIU/L for high risk)
Free T4	Within normal range	Normal to slightly elevated
Free T3	Within normal range	Normal

Antithyroid Drugs

Drug	Mechanism	Onset	Indications	Key Adverse Effects
Methimazole (MMI)	Inhibits thyroid peroxidase (blocks T4/T3 synthesis)	3-4 weeks	Graves disease, toxic nodule (first-line in US, Europe)	Agranulocytosis (0.3-0.6%), hepatotoxicity, arthralgia, cholestatic jaundice, aplasia cutis (in pregnancy)
Propylthiouracil (PTU)	Inhibits TPO + blocks peripheral T4-to-T3 conversion	3-4 weeks	Graves (first trimester pregnancy), thyroid storm	Agranulocytosis, severe hepatotoxicity (more than MMI), ANCA-positive vasculitis
Iodine (SSKI, Lugol’s solution)	Wolff-Chaikoff effect (inhibits T4 release)	1-2 days	Thyroid storm, preoperative thyroidectomy	Rash, salivary gland swelling, GI upset, brassy taste

Beta-Blockers in Thyroid Disease

Drug	Indication	Dosing	Notes
Propranolol (non-selective)	Thyroid storm, symptomatic hyperthyroidism	20-80 mg PO q6h or 1-2 mg IV	Blocks T4-to-T3 conversion at high doses
Atenolol (beta-1 selective)	Symptomatic hyperthyroidism	25-100 mg daily	Safer in asthma/COPD

Corticosteroids

Glucocorticoid Comparison

Drug	Anti-inflammatory Potency	Mineralocorticoid Potency	Equivalent Dose (mg)	Half-Life (plasma)	Duration of Action
Hydrocortisone	1	1	20	90 min	Short (8-12 hours)
Prednisone	4	0.3	5	60 min	Intermediate (12-36 hours)
Prednisolone	4	0.3	5	2-4 hours	Intermediate
Methylprednisolone	5	0	4	1-3 hours	Intermediate
Triamcinolone	5	0	4	2-5 hours	Intermediate
Betamethasone	25	0	0.75	3-5 hours	Long (36-54 hours)
Dexamethasone	30	0	0.75	3-5 hours	Long (36-54 hours)
Fludrocortisone	10	125	NA	3-5 hours	Long (24 hours)

Corticosteroid Adverse Effects

System	Adverse Effect	Risk Factors	Prevention/Management
Metabolic	Weight gain, central obesity, hyperglycemia, diabetes	High dose, prolonged use, obesity, family history	Screen glucose, diet, exercise, insulin/oral agents
Musculoskeletal	Osteoporosis, avascular necrosis, myopathy	Cumulative dose >5 g prednisone, age >50, postmenopausal	Calcium, vitamin D, bisphosphonates; minimize dose and duration
Cardiovascular	Hypertension, fluid retention, accelerated atherosclerosis	Dose, duration, pre-existing HTN	BP monitoring, sodium restriction, antihypertensives
GI	Peptic ulcer, gastritis, pancreatitis (rare)	NSAID co-use, high dose, prior ulcer	PPI/H2RA if also using NSAIDs
Immune	Immunosuppression, infection risk	High dose, prolonged use, combination immunosuppression	Vaccination (avoid live), infection prophylaxis
Dermatologic	Skin thinning, easy bruising, striae, acne, hirsutism	Dose, duration, individual susceptibility	Sun protection, topical retinoids
Neuro-Psychiatric	Mood changes, insomnia, depression, psychosis, euphoria	High dose, pre-existing mental illness	Dose reduction, psychiatric referral
Ocular	Cataracts (posterior subcapsular), glaucoma	Dose, duration, age	Screen for cataracts, IOP monitoring
Adrenal suppression	HPA axis suppression, adrenal crisis with stress	>3 weeks of supraphysiologic dose (>5 mg prednisone/day)	Slow taper over weeks-months; stress-dose steroids

Tapering Regimens

Duration of Use	Taper Strategy	Example
<3 weeks	No taper needed (rapid cessation safe)	Stop abruptly
3-4 weeks	Rapid taper	Reduce by 5 mg prednisone q3-7 days
1-3 months	Moderate taper	Reduce by 2.5-5 mg q1-2 weeks
3-6 months	Slow taper	Reduce by 1-2.5 mg q2-4 weeks
>6 months	Very slow taper	Reduce by 1 mg q4 weeks or transition to q.o.d. then slow reduction

Sex Hormones

Estrogens

Preparation	Type	Route	Common Dose	Indications
17-beta-estradiol	Bioidentical	Oral, transdermal, gel, vaginal	0.5-2 mg PO, 25-100 mcg patch	Menopause HT, hypogonadism
Conjugated equine estrogens (CEE)	Complex mixture (Premarin)	Oral, vaginal	0.3-1.25 mg PO	Menopause HT
Ethinyl estradiol	Synthetic	Oral (in COCs)	10-35 mcg	Contraception
Estradiol valerate	Synthetic prodrug	Oral, IM	1-2 mg PO, 5-20 mg IM	Menopause HT, transgender

Progestins

Preparation	Androgenic Activity	Route	Common Dose	Indications
Medroxyprogesterone acetate (MPA)	Low	Oral, IM (Depo-Provera)	2.5-10 mg PO, 150 mg IM q3months	HRT, contraception, amenorrhea
Norethindrone/norethisterone	Moderate	Oral, implant	0.35-5 mg PO	Contraception (mini-pill), HRT
Levonorgestrel	High	Oral, IUD	0.75-1.5 mg PO (EC), IUD	Contraception, emergency contraception
Progesterone (micronized)	None (bioidentical)	Oral, vaginal, IM	100-200 mg PO, 200 mg PV	HRT, luteal support, threatened abortion
Drospirenone	Anti-androgenic	Oral (COC)	3 mg	Contraception, PMDD

Androgens

Drug	Route	Half-Life	Dose	Indications
Testosterone cypionate/enanthate	IM	8-10 days	50-200 mg q2-4 weeks	Male hypogonadism
Testosterone gel (AndroGel, Testim)	Transdermal	3-6 hours	25-100 mg daily	Male hypogonadism
Testosterone patches	Transdermal	3-6 hours	2-6 mg daily	Male hypogonadism
Testosterone undecanoate	Oral, IM (long-acting)	1-2 hours (PO), 30 days (IM)	750 mg IM, repeat at 4 weeks, then q10 weeks	Male hypogonadism
Methyltestosterone	Oral	3-4 hours	10-50 mg daily	Rarely used (hepatotoxicity)
Danazol	Oral (synthetic androgen)	5-8 hours	200-800 mg daily	Endometriosis, hereditary angioedema

Oral Contraceptives

Combination Oral Contraceptives (COCs)

Generation	Estrogen	Progestin	Androgenic Activity	Key Features
First	EE 50 mcg	Norethindrone, ethynodiol diacetate	High	Higher estrogen dose, higher thromboembolism risk
Second	EE 30-35 mcg	Levonorgestrel, norgestrel	Moderate	Lower VTE risk than 3rd/4th gen; preferred for most women
Third	EE 20-30 mcg	Desogestrel, gestodene, norgestimate	Low	Higher VTE risk than 2nd gen; better acne control
Fourth	EE 20-30 mcg	Drospirenone, dienogest	Anti-androgenic	Anti-mineralocorticoid (drospirenone); VTE risk higher?; PMDD indication
Fifth	EE 20 mcg	Nomacestrol acetate	Minimal	Newest; VTE risk similar to 3rd gen

Non-Oral Contraceptives

Method	Hormone	Duration	Pearl Index (Effectiveness)	Key Advantages
Etonogestrel implant (Nexplanon)	Progestin only	3 years	0.05%	Highest efficacy LARC; no compliance issues
Levonorgestrel IUD (Mirena, Kyleena, Skyla)	Progestin only	3-7 years	0.1-0.4%	Highly effective, reduced bleeding, long-acting
Copper IUD (Paragard)	Non-hormonal	10-12 years	0.8%	No hormones; emergency contraception (5 days)
DMPA (Depo-Provera)	Progestin only	3 months	0.2% (perfect), 6% (typical)	Convenient; weight gain, bone density loss with long-term use
Progestin-only pill (POP, mini-pill)	Progestin only	Daily	0.3% (perfect), 9% (typical)	No estrogen; strict timing required (3-hour window)
Contraceptive patch (Xulane)	EE + norelgestromin	Weekly (3 weeks on, 1 off)	0.3% (perfect), 9% (typical)	Weekly dosing; less GI absorption concerns
Vaginal ring (NuvaRing)	EE + etonogestrel	3 weeks in, 1 week out	0.3% (perfect), 9% (typical)	Monthly; low systemic exposure

Emergency Contraception

Method	Timing	Efficacy (% reduction in pregnancy)	Mechanism	Access
Levonorgestrel (Plan B)	Up to 72 hours (some efficacy up to 120h)	85-90% within 72h	Delays ovulation	OTC (all ages)
Ulipristal (Ella)	Up to 120 hours	95-98% within 120h (more effective than LNG throughout window)	Delays ovulation, may inhibit follicular rupture	Prescription required
Copper IUD	Up to 120 hours	>99%	Prevents fertilization/implantation	Insertion by clinician

Diabetes Medications

Insulin Preparations

Insulin Type	Onset	Peak	Duration	Examples	Characteristics
Rapid-acting	5-15 min	30-90 min	3-5 hours	Lispro (Humalog), aspart (Novolog), glulisine (Apidra)	Covers meal-time glucose; dose at start of meal
Short-acting	30-60 min	2-4 hours	5-8 hours	Regular (Humulin R, Novolin R)	IV use for DKA, pre-meal (30 min before)
Intermediate-acting	1-3 hours	4-8 hours	12-16 hours	NPH (Humulin N, Novolin N)	Basal coverage; variable absorption
Long-acting	1-2 hours	No pronounced peak	18-24 hours	Glargine (Lantus, Basaglar, Toujeo), Detemir (Levemir)	Once-daily basal; more consistent than NPH
Ultra-long acting	1-2 hours	No peak	>36 hours	Degludec (Tresiba)	Once-daily; very stable; flexible dosing
Pre-mixed	Depends on composition	Mixed	Mixed	70/30 NPH/Regular, 75/25 lispro protamine/lispro	Convenient; less flexible

Non-Insulin Diabetes Medications

Class	Mechanism	HbA1c Reduction	Weight Effect	Hypoglycemia Risk	Key Notes
Metformin	AMPK activation, hepatic glucose output reduction	1-1.5%	Neutral/loss	Very low	First-line T2DM; GI intolerance; lactic acidosis (rare)
Sulfonylureas	K-ATP closure, insulin secretion	1-1.5%	Gain	Moderate-high	Inexpensive; glipizide, glimepiride, glyburide
Thiazolidinediones (TZDs)	PPAR-gamma agonism	0.8-1.2%	Gain	Low	Pioglitazone, rosiglitazone; fluid retention, fractures, bladder cancer concern
DPP-4 inhibitors	GLP-1 degradation inhibition	0.6-0.8%	Neutral	Very low	Sitagliptin, saxagliptin, linagliptin; well-tolerated
GLP-1 RAs	GLP-1 receptor activation	1-2%	Loss (3-15 lbs)	Low (unless with insulin/sulfonylurea)	Liraglutide, semaglutide, tirzepatide (GIP/GLP-1); CV benefit
SGLT2 inhibitors	Renal glucose excretion	0.8-1%	Loss (3-6 lbs)	Low	Empagliflozin, dapagliflozin, canagliflozin; CV, HF, CKD benefit
Meglitinides	K-ATP closure (short-acting)	0.5-1%	Gain	Moderate	Repaglinide, nateglinide; prandial dosing
Alpha-glucosidase inhibitors	Alpha-glucosidase inhibition	0.5-0.8%	Neutral	Low	Acarbose, miglitol; GI side effects, post-prandial glucose
Bile acid sequestrants	Bile acid binding	0.3-0.5%	Loss	Low	Colesevelam; constipation, LDL reduction

Growth Hormone and Analogues

Drug	Mechanism	Indications	Dose	Key Adverse Effects
Somatropin (r-hGH)	GH receptor activation	GH deficiency, Turner, Prader-Willi, CKD, SGA	0.15-0.3 mg/kg/week SC (divided doses)	Arthralgia, edema, carpal tunnel, pseudotumor cerebri, glucose intolerance
Somatostatin analogs (octreotide, lanreotide)	Somatostatin receptor agonism (SSTR2, SSTR5)	Acromegaly, NETs, GI bleeding (octreotide)	Octreotide 20-30 mg IM q4weeks (LAR); Lanreotide 90-120 mg SC q4weeks	Gallstones, bradycardia, hypoglycemia/hyperglycemia, GI upset
Pegvisomant	GH receptor antagonist	Acromegaly (resistant)	10-40 mg SC daily	Hepatotoxicity, lipodystrophy

Conclusion

Hormonal therapies are diverse and potent medications requiring careful consideration of indications, dosing, monitoring, and adverse effects. Thyroid hormone replacement, corticosteroids, sex hormone therapies, and diabetes medications are among the most commonly prescribed drugs. Understanding feedback mechanisms, receptor selectivity, and drug-specific adverse effect profiles is essential for safe and effective use. Hormonal therapies for cancer (tamoxifen, aromatase inhibitors, GnRH agonists) demonstrate the therapeutic role of hormone modulation beyond replacement and endocrine disorders.