Hormone optimization: what the guidelines say about TRT and hormone therapy

“Optimize” and “balance” are two words that sound like clinical goals and are not. Neither describes an outcome you can measure in a blood test. What the reference guidelines describe is something else: a diagnosis — symptoms plus confirmed hormone concentrations — and a treatment with specific indications, person-dependent risks and periodic follow-up.

This article gathers what the Endocrine Society says about testosterone and what the North American Menopause Society says about hormone therapy. With the trial figures and their funders.

The clinical programmes are here: men's hormonal health and women's hormonal health.

“Balancing hormones” is not a measurable outcome

When a text promises to “balance testosterone, estradiol and progesterone”, it is describing a feeling, not a criterion. What can be measured is the concentration of a hormone in blood at a given moment, and what can be assessed is a symptom or a clinical parameter — bone mineral density, hot flushes, haemoglobin, lean mass. The difference matters because it is what separates a treatment from a promise.

And there is a second difference, the one marketing skips most often: treating a deficiency is not the same as raising a number that is already in range. The guidelines are explicit on that point, and that is as far as they go.

Men: when testosterone is a treatment

The Endocrine Society clinical practice guideline (2018, DOI `10.1210/jc.2018-00229`) sets the diagnostic criterion in two conditions that must both hold:

1. Symptoms and signs consistent with testosterone deficiency.
2. Unequivocally and consistently low serum testosterone, measured fasting in the morning with a reliable assay, and confirmed with a second measurement.

If the total value sits near the lower limit of normal, or a condition alters sex hormone-binding globulin, the guideline also recommends obtaining free testosterone. The order is not negotiable: symptom first, repeated lab second, treatment only then.

That rules out, by definition, the idea of “optimizing” someone who does not have a deficiency: the indication is not a number to reach, it is a diagnosis to confirm.

What has been measured about the heart

The historical fear about testosterone and the heart has a trial that answers it: TRAVERSE, published in *The New England Journal of Medicine* in 2023 (DOI `10.1056/NEJMoa2215025`).

Feature	Detail
Population	5,246 men aged 45 to 80, with hypogonadism symptoms, two fasting testosterone readings below 300 ng/dL, and preexisting cardiovascular disease or high risk
Design	Randomised, double-blind, placebo-controlled, noninferiority
Treatment	Transdermal 1.62% gel, adjusted to maintain levels between 350 and 750 ng/dL
Mean duration	21.7 months of treatment; 33 months of follow-up
Primary endpoint	Cardiovascular death, nonfatal myocardial infarction or nonfatal stroke: 7.0% with testosterone versus 7.3% with placebo (hazard ratio 0.96; 95% CI 0.78–1.17)
Funding	AbbVie

The trial's conclusion is that, in that specific population, testosterone was noninferior to placebo for major adverse cardiac events. That is an important safety finding and one of the most cited. Its limits too: it measures cardiovascular safety in men with hypogonadism and cardiovascular risk, not benefits in men with normal levels, and it is funded by a testosterone manufacturer.

A noninferiority trial means exactly that: no greater harm than placebo was demonstrated in that group. It does not mean it improves anyone's cardiovascular health, and that distinction is frequently lost.

Women: what NAMS says about hormone therapy

The 2022 position statement of the North American Menopause Society (DOI `10.1097/GME.0000000000002028`) summarises the state of the question with a precision worth reproducing almost literally:

• Hormone therapy remains the most effective treatment for vasomotor symptoms and the genitourinary syndrome of menopause, and has been shown to prevent bone loss and fracture.
• Risks differ by type, dose, duration, route of administration, timing of initiation, and whether a progestogen is used.
• Treatment should be individualised with the best available evidence to maximise benefits and minimise risks, with periodic reassessment.
• In women younger than 60 or within 10 years of menopause onset, without contraindications, the benefit-risk ratio is favourable for bothersome hot flushes and prevention of bone loss.
• If therapy starts more than 10 years after menopause or after age 60, the benefit-risk ratio appears less favourable, due to greater absolute risks of coronary heart disease, stroke, venous thromboembolism and dementia.

Behind those recommendations sits the trial that changed practice: the Women's Health Initiative (JAMA, 2002, DOI `10.1001/jama.288.3.321`), whose results forced a review of widespread hormone therapy use and a shift from a population recommendation to an individual decision. The lesson of the two following decades is condensed in one word: “individualise”.

What no guideline supports

• Longevity. None of the guidelines cited proposes hormone therapy as a treatment to extend life or reverse ageing.
• “Optimizing” someone with no deficiency. The indication is a confirmed diagnosis, not a desired number.
• Promising energy, libido or bone density. Those parameters are measured in studies with specific populations and criteria; they are not a guaranteed result for one person.
• Doses and schedules. You will find no dosage figure in this article, for testosterone or hormone therapy. That is a clinical act.
• The word “bioidentical” as a synonym for better. The hormone type is a clinical decision among several; NAMS asks for individualisation, it does not name a superior formulation.

On the other end of the spectrum — the peptides marketed for the same territory — see Sermorelin and NAD+: what has actually been measured in cellular longevity.

How treatment starts

With a consultation and a lab panel, in that order. The evaluation covers symptoms, history, contraindications and concurrent medication; the lab work confirms or rules out the diagnosis; and then treatment is adjusted with periodic follow-up, because risks and benefits are reassessed over time.

State coverage is on the territorial coverage page: 49 states — all but California — plus Washington D.C. and Puerto Rico.

Frequently asked questions

Can I “optimize” my testosterone if my lab result is in the normal range?

Not as clinical treatment. The Endocrine Society conditions the diagnosis on consistent symptoms and unequivocally low concentrations confirmed by a second measurement. Raising a number that is already in range is not an indication the guideline supports.

Is testosterone dangerous for the heart?

In men with hypogonadism and preexisting cardiovascular disease or high risk, TRAVERSE found testosterone to be noninferior to placebo for major adverse cardiac events (7.0% versus 7.3%). That is a safety finding in that population, not proof of cardiovascular benefit.

Does hormone therapy cause cancer?

Risks depend on type, dose, duration, route and timing of initiation, and on whether a progestogen is combined. NAMS insists on individualising and reassessing periodically. The question has no single answer, and anyone giving you one should tell you which formulation and which context they mean.

Does hormone therapy rejuvenate?

No. It is the most effective treatment for vasomotor symptoms and the genitourinary syndrome of menopause, and it prevents bone loss. No guideline proposes it as an anti-ageing treatment.

Where can I get the evaluation?

In the men's hormonal health and women's hormonal health programmes. State availability is on the territorial coverage page.

Sources

1. Testosterone Therapy in Men With Hypogonadism: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocrinol. Metab. 2018. DOI `10.1210/jc.2018-00229`. PMID 29562364. Source of the diagnostic criterion (symptoms + two fasting morning measurements).
2. Cardiovascular Safety of Testosterone-Replacement Therapy. N. Engl. J. Med. 2023. DOI `10.1056/NEJMoa2215025`. PMID 37326322. Population, design, results and funding (AbbVie) taken from the indexed abstract.
3. The 2022 hormone therapy position statement of The North American Menopause Society. Menopause. 2022. DOI `10.1097/GME.0000000000002028`. PMID 35797481. Indications, risk-modifying factors and therapeutic window.
4. Risks and Benefits of Estrogen Plus Progestin in Healthy Postmenopausal Women (Women's Health Initiative). JAMA. 2002. DOI `10.1001/jama.288.3.321`. Historical context of the change in practice.
5. FDA — Human Drug Compounding Laws. `https://www.fda.gov/drugs/human-drug-compounding/compounding-laws-and-policies`. Regime applicable when therapy is dispensed as a compounded formulation.

Medical Disclaimer: *The information provided in this article is for educational and informational purposes only and does not constitute medical advice, diagnosis, or treatment. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. Always consult your physician before making any changes to your medication or lifestyle regimen.*