Andropause Symptoms: Labs to Order and Next Steps

What Andropause Actually Means in Clinical Terms

Andropause is not a sudden hormonal cliff like female menopause. It is a gradual, age-related decline in testosterone and bioavailable androgens that the Endocrine Society defines as late-onset hypogonadism (LOH). Total testosterone drops approximately 1% to 2% per year after age 30, while sex hormone-binding globulin (SHBG) rises, compressing the free fraction even faster [1].

The European Male Ageing Study (EMAS), which followed 3,369 men aged 40 to 79, found that only 2.1% met strict criteria for LOH: total testosterone below 317 ng/dL (11 nmol/L) combined with at least three sexual symptoms [2]. That number climbs above 5% in men over 70. Obesity is the single strongest modifiable risk factor. A BMI above 30 doubles the odds of biochemical hypogonadism independent of age, because excess adipose tissue upregulates aromatase, converting testosterone to estradiol [3].

The distinction between primary hypogonadism (testicular failure, with elevated LH) and secondary hypogonadism (hypothalamic-pituitary suppression, with low or inappropriately normal LH) matters for treatment. Most age-related LOH is secondary or mixed, often worsened by medications like opioids, comorbidities including type 2 diabetes, or obstructive sleep apnea [1].

Recognizing the Symptom Cluster

No single symptom confirms andropause. The diagnosis relies on a pattern. The EMAS cohort identified three symptoms with the highest specificity for low testosterone: poor morning erections, low sexual desire, and erectile dysfunction [2]. These sexual symptoms showed a syndromic association with testosterone below 317 ng/dL that physical symptoms like fatigue did not match independently.

Other common presentations include depressed or irritable mood, difficulty concentrating, reduced motivation, loss of body hair, increased visceral fat, and decreased bone mineral density. Sleep disturbances are frequent but bidirectional: poor sleep lowers testosterone, and low testosterone disrupts sleep architecture. A 2011 JAMA study of 1,312 men showed that sleeping five hours per night instead of eight reduced daytime testosterone by 10% to 15% within one week [4].

The Androgen Deficiency in the Aging Male (ADAM) questionnaire and the Aging Males' Symptoms (AMS) scale are screening tools, but neither replaces lab confirmation. The ADAM questionnaire has a sensitivity of 88% but a specificity of only 60%, meaning false positives are common [5]. A positive screen should trigger lab work, not a diagnosis.

Which Labs to Order and Why

The 2018 Endocrine Society Clinical Practice Guideline recommends measuring total testosterone on two separate mornings, fasting, before 10:00 AM [1]. Testosterone follows a circadian rhythm that peaks between 6:00 and 8:00 AM and can drop 20% to 25% by afternoon. Eating, particularly a high-fat meal, suppresses levels acutely.

A total testosterone below 300 ng/dL (10.4 nmol/L) on both draws confirms biochemical hypogonadism. Values between 200 and 300 ng/dL are unequivocally low. The 200 to 400 ng/dL gray zone requires clinical correlation with symptoms and often a free or bioavailable testosterone calculation.

Core panel:

• Total testosterone (two fasting AM draws, immunoassay or LC-MS/MS)
• Free testosterone (calculated via Vermeulen equation using total T, SHBG, and albumin) or equilibrium dialysis
• LH and FSH to distinguish primary from secondary hypogonadism
• SHBG to interpret total testosterone in context (elevated SHBG in aging, liver disease, or hyperthyroidism inflates total T while free T is genuinely low)
• Prolactin to screen for pituitary adenoma if testosterone is below 150 ng/dL or LH is suppressed
• CBC with hematocrit (baseline before TRT, since testosterone stimulates erythropoiesis)
• Comprehensive metabolic panel including fasting glucose
• PSA (baseline prostate screening before initiating TRT)

Conditional add-ons:

• Estradiol (sensitive assay) if gynecomastia is present or BMI exceeds 30
• Thyroid panel (TSH, free T4) if fatigue is the dominant complaint
• Iron studies and ferritin to rule out hemochromatosis, which can cause secondary hypogonadism
• DEXA scan if fragility fracture history or testosterone is persistently below 200 ng/dL
• Pituitary MRI if prolactin is elevated or testosterone is below 150 ng/dL with low LH

Dr. Bradley Anawalt, an endocrinologist at the University of Washington, has noted: "The diagnosis of male hypogonadism should never rest on a single testosterone measurement. Biological variability alone can swing levels by 15% to 20% between draws" [1].

Ruling Out Mimics and Secondary Causes

Low testosterone is often a downstream effect, not the root problem. Before assuming primary or age-related LOH, clinicians need to rule out reversible suppressors. The American Urological Association (AUA) guideline lists these common culprits [6]:

Medications that suppress testosterone:

• Chronic opioids reduce testosterone in 50% to 90% of long-term users via hypothalamic GnRH suppression [7]
• Glucocorticoids (prednisone above 7.5 mg/day chronically)
• Ketoconazole and spironolactone (direct gonadal inhibition)
• GnRH agonists used for prostate cancer

Comorbidities linked to secondary hypogonadism:

• Obesity (BMI >30 increases aromatase activity)
• Type 2 diabetes: the Testosterone Trials enrolled men with average total testosterone of 232 ng/dL, and 40% had type 2 diabetes or prediabetes [8]
• Obstructive sleep apnea
• Chronic kidney disease
• HIV/AIDS
• Hemochromatosis

Treating these underlying conditions can raise testosterone by 100 to 200 ng/dL without exogenous hormone therapy. Weight loss is particularly effective. A meta-analysis of 24 studies (N=1,285) found that each unit drop in BMI corresponded to a testosterone increase of approximately 2.93 nmol/L (84 ng/dL) [3].

Lifestyle Interventions Before or Alongside TRT

The Endocrine Society recommends addressing modifiable factors before initiating TRT in men with borderline levels (250 to 350 ng/dL) [1]. These are not optional footnotes. They can be sufficient on their own for men in the gray zone.

Resistance training is the single most evidence-backed behavioral intervention. A 12-week progressive resistance program in men aged 60 to 75 raised free testosterone by 16% in a controlled trial published in the Journal of Clinical Endocrinology & Metabolism [9]. Compound movements (squats, deadlifts, bench press) at 70% to 85% of one-rep max for 3 to 4 sessions per week produce the most consistent hormonal response.

Sleep optimization targets the circadian testosterone peak. Men sleeping fewer than six hours per night have testosterone levels equivalent to men 10 to 15 years older [4]. Prioritizing 7 to 9 hours, maintaining consistent wake times, and treating sleep apnea if present are non-negotiable baseline steps.

Weight loss in obese men produces the largest testosterone rebound. A secondary analysis from the Diabetes Prevention Program (N=1,653) showed that lifestyle intervention increased total testosterone by 2.20 nmol/L (63 ng/dL) at one year compared to placebo, while metformin increased it by 1.30 nmol/L (37 ng/dL) [10].

Alcohol reduction matters at the threshold most men overlook. Consuming more than 14 standard drinks per week suppresses Leydig cell function. Even moderate intake (7 to 14 drinks/week) correlates with lower free testosterone in population studies [11].

When TRT Is the Right Next Step

TRT becomes appropriate when two confirmed low testosterone readings coincide with persistent symptoms despite 3 to 6 months of lifestyle optimization, or when testosterone is below 200 ng/dL with clear clinical manifestations [1][6].

Available formulations include:

| Route | Example | Dosing | Steady State | |---|---|---|---| | Intramuscular injection | Testosterone cypionate 200 mg/mL | 100 to 200 mg every 1 to 2 weeks | 2 to 4 weeks | | Transdermal gel | AndroGel 1.62% | 20.25 to 81 mg daily | 2 to 4 weeks | | Transdermal patch | Androderm 2 to 4 mg | Daily application | 2 to 4 weeks | | Nasal gel | Natesto 5.5 mg/actuation | Three times daily | Days | | Subcutaneous pellets | Testopel 75 mg pellets | 150 to 450 mg every 3 to 6 months | 1 month | | Oral | Jatenzo (testosterone undecanoate) | 158 to 396 mg twice daily | 1 week |

The Testosterone Trials (TTrials), a coordinated set of seven placebo-controlled studies enrolling 790 men aged 65 and older with testosterone below 275 ng/dL, demonstrated that one year of transdermal testosterone gel improved sexual function (measured by the PDQ-Q4 score, P<0.001), physical activity (6-minute walk distance increased by 6.1 meters, P=0.04 in the Physical Function Trial), and mood (PHQ-9 depression scores improved in men with baseline depressive symptoms) [8].

A 2023 NEJM study, the TRAVERSE trial (N=5,246), confirmed that TRT in men aged 45 to 80 with hypogonadism and cardiovascular risk factors did not increase the incidence of major adverse cardiovascular events (MACE) compared to placebo (hazard ratio 0.96 to 95% CI 0.78 to 1.17) [12]. This trial resolved decades of cardiovascular safety concerns that had limited prescribing confidence.

Absolute and Relative Contraindications

TRT is contraindicated in men with [6]:

• Metastatic prostate cancer or breast cancer
• Hematocrit above 54% (risk of polycythemia and thrombosis)
• Untreated severe obstructive sleep apnea
• Uncontrolled heart failure (NYHA Class IV)
• Active desire for fertility (exogenous testosterone suppresses spermatogenesis via HPG axis feedback)

For men who want to preserve fertility, alternatives include clomiphene citrate (off-label, 25 to 50 mg every other day), which stimulates endogenous LH and FSH secretion, or human chorionic gonadotropin (hCG) at 1,500 to 3 to 000 IU two to three times per week [6]. These maintain intratesticular testosterone while avoiding the azoospermia risk of exogenous TRT.

The AUA guideline states: "Clinicians should inform patients that testosterone therapy may result in irreversible reduction of spermatogenesis and should discuss sperm banking before treatment" [6].

Monitoring on TRT: The 3-6-12 Schedule

Monitoring prevents complications and confirms therapeutic response. The Endocrine Society recommends [1]:

At 3 months:

• Total testosterone (trough level for injections; any-time for gels if applied that morning)
• Hematocrit (if above 54%, reduce dose or switch to a shorter-acting formulation, or perform therapeutic phlebotomy)
• Symptom reassessment using a validated instrument (qADAM or AMS)

At 6 months:

• Repeat testosterone and hematocrit
• PSA (if baseline was above 1.5 ng/mL or patient is over 40)
• Liver function (for oral formulations only)

At 12 months and annually thereafter:

• Testosterone, hematocrit, PSA
• DEXA scan if osteopenia was present at baseline
• Lipid panel (testosterone can modestly lower HDL by 5% to 10%)
• Symptom assessment

Target testosterone on therapy is 450 to 600 ng/dL for most men. Levels above 1 to 000 ng/dL increase polycythemia risk without additional symptom benefit in clinical trials [1].

What to Do This Week If You Suspect Andropause

If you are experiencing at least three of the symptoms discussed, and you are over 40, request a fasting morning testosterone draw from your primary care provider or through a telehealth service. Do not accept a single afternoon value as diagnostic. If your total testosterone is below 300 ng/dL, repeat it within two to four weeks along with LH, SHBG, prolactin, CBC, and PSA. Bring the results to a physician who can evaluate whether lifestyle changes alone are appropriate or whether TRT is warranted based on your symptom burden, comorbidities, and reproductive plans.