Top Clinical Evidence for Physicians

Does hormone replacement therapy increase breast

Does hormone replacement therapy increase breast cancer risk?

Combined estrogen-progestin therapy is associated with a small increased breast cancer risk in WHI and observational data. Estrogen-alone in hysterectomized women showed lower risk in WHI, but interpretation depends on regimen, duration, and individual risk factors.

Counsel on regimen-specific breast cancer risk: combined estrogen-progestin differs from estrogen alone in hysterectomized women.

Does hormone replacement therapy increase breast cancer risk? →

Does testosterone therapy suppress fertility in

Does testosterone therapy suppress fertility in men?

Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis and reliably reduces spermatogenesis. Recovery after discontinuation is variable and may be incomplete in some men.

Men who desire near-term fertility should not start exogenous testosterone without specialist evaluation.

Does testosterone therapy suppress fertility in men? →

Does testosterone replacement increase cardiovascular risk

Does testosterone replacement increase cardiovascular risk?

Large randomized data (including TRAVERSE) do not show a significant increase in major adverse cardiovascular events with testosterone therapy in hypogonadal men over median follow-up of roughly three years. Older observational studies conflict, and absolute risk depends on baseline cardiovascular disease, formulation, and monitoring.

For men with diagnosed hypogonadism and appropriate indication, testosterone therapy should not be withheld solely because of historical cardiovascular concerns.

Does testosterone replacement increase cardiovascular risk? →

Do GLP-1 receptor agonists reduce major

Do GLP-1 receptor agonists reduce major cardiovascular events?

GLP-1 receptor agonists with cardiovascular outcome trials (including liraglutide and semaglutide in selected populations) reduce major adverse cardiovascular events beyond glucose lowering in high-risk patients with type 2 diabetes or obesity.

Prioritize GLP-1 receptor agonists with proven cardiovascular benefit in high-risk type 2 diabetes or obesity when cardiometabolic risk reduction is a treatment goal.

Do GLP-1 receptor agonists reduce major cardiovascular events? →

Is ApoB more useful than LDL-C

Is ApoB more useful than LDL-C for cardiovascular risk prediction?

Prospective cohorts and meta-analyses suggest ApoB may capture atherogenic particle burden better than LDL-C alone, particularly when triglycerides are elevated or LDL particles are discordant with LDL-C.

Use ApoB when LDL-C and clinical risk discord, particularly with elevated triglycerides or small dense LDL patterns.

Is ApoB more useful than LDL-C for cardiovascular risk prediction? →

Does elevated lipoprotein(a) independently increase cardiovascular

Does elevated lipoprotein(a) independently increase cardiovascular risk?

Mendelian randomization and epidemiologic data support Lp(a) as a causal cardiovascular risk factor. Specific Lp(a)-lowering therapies are emerging but routine treatment beyond standard risk factor control awaits outcome trial confirmation.

Measure lipoprotein(a) once in patients with premature cardiovascular disease or strong family history.

Does elevated lipoprotein(a) independently increase cardiovascular risk? →

Does menopausal hormone therapy prevent osteoporosis

Does menopausal hormone therapy prevent osteoporosis and fractures?

Estrogen-based therapy reduces bone loss and fracture risk in postmenopausal women, with benefit most established during early postmenopause. Guidelines support HRT for fracture prevention primarily when indicated for vasomotor symptoms or in high-risk women.

Use estrogen-based therapy for fracture prevention primarily when vasomotor symptoms or other indications already justify treatment, or when osteoporosis risk is high.

Does menopausal hormone therapy prevent osteoporosis and fractures? →

How does tirzepatide compare with semaglutide

How does tirzepatide compare with semaglutide for weight loss?

Head-to-head trials suggest tirzepatide produces greater average weight loss than semaglutide at studied doses, with broadly similar gastrointestinal side-effect profiles. Long-term cardiovascular outcome comparisons are ongoing.

Choose between tirzepatide and semaglutide based on weight-loss goals, tolerability, access, and comorbidity rather than assuming equivalence.

How does tirzepatide compare with semaglutide for weight loss? →

Should adults take statins for primary

Should adults take statins for primary cardiovascular prevention?

Meta-analyses of primary prevention trials show reduced major adverse cardiovascular events with statins in appropriately selected moderate-to-high-risk adults. Shared decision-making should weigh absolute risk reduction against side effects and patient preference.

Calculate absolute cardiovascular risk and discuss expected benefit versus myalgia, diabetes, and patient preference before starting statin primary prevention.

Should adults take statins for primary cardiovascular prevention? →

Should aspirin be used for primary

Should aspirin be used for primary cardiovascular prevention?

Current guidelines generally discourage routine aspirin for primary prevention in low-to-moderate-risk adults because bleeding harm offsets modest benefit. Select high-risk individuals may still be considered with shared decision-making.

Avoid routine aspirin for primary prevention in low-to-moderate-risk adults given bleeding risk.

Should aspirin be used for primary cardiovascular prevention? →

Does testosterone therapy increase hematocrit and

Does testosterone therapy increase hematocrit and polycythemia risk?

Testosterone therapy commonly raises hematocrit; polycythemia is a recognized adverse effect requiring dose adjustment, formulation changes, or phlebotomy when thresholds are exceeded.

Check hematocrit before initiation and at regular intervals after starting testosterone.

Does testosterone therapy increase hematocrit and polycythemia risk? →

Does vitamin D supplementation reduce mortality

Does vitamin D supplementation reduce mortality or major disease?

Meta-analyses show vitamin D supplementation does not significantly reduce all-cause mortality in unselected populations. Targeted repletion may benefit those with documented deficiency.

Test and replete documented vitamin D deficiency rather than supplementing unselected populations for mortality prevention.

Does vitamin D supplementation reduce mortality or major disease? →

Does hormone replacement therapy increase venous

Does hormone replacement therapy increase venous thromboembolism risk?

Oral estrogen increases venous thromboembolism risk compared with no therapy. Transdermal estrogen appears to carry lower thrombotic risk in observational studies and is often preferred in women at elevated VTE risk.

Prefer transdermal estrogen in women with elevated thrombotic risk, obesity, or prior VTE when systemic estrogen is indicated.

Does hormone replacement therapy increase venous thromboembolism risk? →

Should subclinical hypothyroidism be treated with

Should subclinical hypothyroidism be treated with levothyroxine?

The TRUST trial found no meaningful symptom or quality-of-life benefit from levothyroxine in older adults with subclinical hypothyroidism. Treatment may still be considered with very high TSH, pregnancy plans, or specific clinical contexts.

Avoid reflex levothyroxine for mild subclinical hypothyroidism in older adults without compelling indication.

Should subclinical hypothyroidism be treated with levothyroxine? →

Do therapies that raise HDL reduce

Do therapies that raise HDL reduce cardiovascular events?

Trials of niacin and CETP inhibitors raised HDL without consistent reduction in cardiovascular events when added to statins, challenging the hypothesis that raising HDL alone is protective.

Do not add niacin or CETP inhibitors solely to raise HDL when LDL is already treated.

Do therapies that raise HDL reduce cardiovascular events? →

Is progestogen required to protect the

Is progestogen required to protect the endometrium with estrogen therapy?

Systemic estrogen in women with a uterus requires adequate progestogen exposure to prevent endometrial hyperplasia. Micronized progesterone and progestins differ in metabolic and VTE profiles.

Any woman with a uterus receiving systemic estrogen needs adequate progestogen exposure to prevent endometrial hyperplasia.

Is progestogen required to protect the endometrium with estrogen therapy? →

Does hormone replacement therapy reduce cardiovascular

Does hormone replacement therapy reduce cardiovascular risk in early menopause?

The timing hypothesis suggests earlier initiation may differ from late initiation, where WHI showed harm for combined therapy. Current guidelines emphasize individualized risk assessment rather than routine cardioprotection.

In early symptomatic menopause, individualize HRT after cardiovascular risk assessment rather than treating hormones as routine primary prevention.

Does hormone replacement therapy reduce cardiovascular risk in early menopause? →

Do patients regain weight after stopping

Do patients regain weight after stopping GLP-1 therapy?

Clinical trials and observational follow-up show substantial weight regain after GLP-1 discontinuation, suggesting chronic therapy may be needed to maintain benefit unless durable lifestyle changes are established.

Counsel that weight regain after GLP-1 discontinuation is common and plan for long-term strategy at initiation.

Do patients regain weight after stopping GLP-1 therapy? →

Does GLP-1 treatment cause meaningful muscle

Does GLP-1 treatment cause meaningful muscle loss?

GLP-1 therapies reduce weight through fat and lean mass loss; lean loss is partly proportional to total weight lost. Resistance training and adequate protein may mitigate but not eliminate lean mass decline.

Pair GLP-1 therapy with resistance training and adequate protein intake to limit lean mass loss during weight reduction.

Does GLP-1 treatment cause meaningful muscle loss? →

Is desiccated thyroid extract superior to

Is desiccated thyroid extract superior to levothyroxine for hypothyroidism?

Levothyroxine is standard first-line therapy with the strongest outcome evidence. Desiccated thyroid extract lacks modern RCT data demonstrating superiority and has variable hormone content between batches.

Use levothyroxine as first-line hypothyroid treatment unless the patient has a documented intolerance after a proper trial.

Is desiccated thyroid extract superior to levothyroxine for hypothyroidism? →

Are PDE5 inhibitors safe for cardiovascular

Are PDE5 inhibitors safe for cardiovascular disease in men with erectile dysfunction?

In stable cardiovascular disease, PDE5 inhibitors do not appear to increase major adverse cardiac events when used appropriately and nitrate co-administration is avoided. Sexual activity itself carries modest cardiovascular demand; individualized assessment remains important after recent events.

In stable cardiovascular disease, PDE5 inhibitors can be used with appropriate counseling when nitrates are not co-prescribed.

Are PDE5 inhibitors safe for cardiovascular disease in men with erectile dysfunction? →

Is daily low-dose tadalafil better than

Is daily low-dose tadalafil better than on-demand dosing for erectile dysfunction?

Both daily low-dose and on-demand tadalafil improve erectile function. Daily dosing may improve spontaneity and lower urinary symptom scores in men with comorbid LUTS, while on-demand dosing minimizes drug exposure for men with infrequent sexual activity.

Match tadalafil dosing to lifestyle and comorbidity: daily low-dose for men wanting spontaneity or with LUTS, on-demand for infrequent activity.

Is daily low-dose tadalafil better than on-demand dosing for erectile dysfunction? →

Does low-dose vaginal estrogen carry significant

Does low-dose vaginal estrogen carry significant systemic risks?

Low-dose vaginal estrogen for genitourinary syndrome of menopause achieves local benefit with minimal systemic absorption in most women. Progestogen is generally not required for endometrial protection at standard low doses.

Low-dose vaginal estrogen is first-line for genitourinary syndrome of menopause in most women, with progestogen generally unnecessary at standard doses.

Does low-dose vaginal estrogen carry significant systemic risks? →

What is the evidence for hormone

What is the evidence for hormone and metabolic therapy in PCOS?

PCOS management prioritizes lifestyle intervention, cycle regulation, and treatment of hyperandrogenism and metabolic risk. Metformin and hormonal contraceptives have evidence for specific endpoints; individualized plans depend on fertility goals.

Anchor PCOS care in lifestyle, cycle regulation, and cardiometabolic risk reduction tailored to fertility goals.

What is the evidence for hormone and metabolic therapy in PCOS? →