Clinical Glossary

The fraction of circulating testosterone not bound to sex hormone-binding globulin (SHBG) or albumin. Free testosterone is the biologically active portion and is often measured when total testosterone is borderline or SHBG is abnormal.

A liver-produced protein that binds testosterone and estradiol in circulation. Elevated SHBG lowers free testosterone; low SHBG raises it. SHBG interpretation is essential when evaluating hypogonadism labs.

A composite cardiovascular endpoint typically including myocardial infarction, stroke, and cardiovascular death. MACE is the primary hard-outcome measure in major cardiovascular outcome trials including TRAVERSE and GLP-1 CVOTs.

A structured framework for framing clinical questions: Population (who), Intervention (what treatment), Comparator (versus what), and Outcome (what endpoint). RAGMD uses PICO-aligned evidence retrieval to match studies to clinical questions.

A surrogate marker of average blood glucose over 2–3 months. HbA1c is widely used in diabetes trials but is a surrogate endpoint — distinct from hard outcomes like MACE, kidney failure, or mortality.

Hormone therapy using molecules structurally identical to endogenous hormones (e.g., estradiol, progesterone, testosterone). Distinct from conjugated equine estrogens or synthetic progestins used in some landmark trials.

Exogenous testosterone administration to treat symptomatic hypogonadism in men. Evidence on cardiovascular safety, prostate risk, fertility, and hematologic effects varies by population, formulation, and endpoint.

Blood clots in veins, including deep vein thrombosis (DVT) and pulmonary embolism (PE). A clinically important safety endpoint in hormone therapy, particularly with oral estrogen routes.

A clinical syndrome of low testosterone with symptoms and signs. Diagnosis requires consistent biochemical confirmation; treatment decisions weigh symptom burden against safety evidence in the patient's risk profile.

The primary estrogen in premenopausal women and a metabolite of testosterone in men. In men on TRT, estradiol management is clinically relevant for symptom control and is debated in cardiovascular risk discussions.

A class of medications that activate the GLP-1 receptor, used for type 2 diabetes and obesity. Major trials (LEADER, SUSTAIN-6, SELECT) established cardiovascular and weight outcomes for specific agents and populations.

A protein found on atherogenic lipoprotein particles. ApoB may predict cardiovascular risk when discordant with LDL-C and is increasingly used in advanced lipid assessment.

Elevated TSH with normal free T4, often without clear symptoms. Treatment benefit in older adults was not established in the TRUST trial for the studied population.

RAGMD's calibrated assessment of how strongly the published literature supports a clinical conclusion — HIGH, MODERATE, or LIMITED. This reflects literature strength, not a treatment recommendation.

A definitive randomized or large observational study that anchors clinical understanding of a question — e.g., TRAVERSE for TRT cardiovascular safety, WHI for HRT risks, SELECT for semaglutide CV outcomes.

A surrogate lipid marker for atherosclerotic risk. LDL-C lowering is associated with reduced cardiovascular events, but ApoB may add prognostic value when discordant with LDL-C.

A class of lipid-lowering drugs that reduce LDL-C and have established cardiovascular benefit in primary and secondary prevention populations.

A class of medications that inhibit renal glucose reabsorption, used in diabetes and heart failure with proven benefits on heart failure hospitalization and renal outcomes.

A laboratory or physical measurement used as a substitute for a patient-important outcome. Surrogate endpoints (e.g., HbA1c, LDL-C, BMD) may not always predict hard outcomes like MACE or fracture.

An experimental study design where participants are randomly assigned to intervention or control groups. RCTs provide the strongest evidence for causal treatment effects when well-conducted.

The life stage after permanent cessation of menstruation. Hormone therapy evidence, risks, and benefits differ substantially between early postmenopausal women and those initiating therapy years after menopause.

The proportion of blood volume occupied by red blood cells. TRT can increase hematocrit; monitoring is a standard safety consideration in testosterone therapy.

FRACTURE is a patient-important hard outcome used in clinical trials and evidence synthesis. RAGMD distinguishes hard outcomes from surrogate markers when weighing study directness.

LDL is a surrogate endpoint used in clinical trials and evidence synthesis. RAGMD distinguishes hard outcomes from surrogate markers when weighing study directness.

BMD is a surrogate endpoint used in clinical trials and evidence synthesis. RAGMD distinguishes hard outcomes from surrogate markers when weighing study directness.

EGFR is a surrogate endpoint used in clinical trials and evidence synthesis. RAGMD distinguishes hard outcomes from surrogate markers when weighing study directness.