Beyond the Laboratory Reference Range: A Psychiatric Guide to Low Testosterone in Men
May 28, 2026
For the mental health clinician, the complaint “I feel tired all the time, and nothing seems to matter anymore” is the currency of daily practice. Yet when this presentation occurs in a male patient, the differential diagnosis must extend beyond the familiar territory of major depressive disorder to include a condition that mimics depression with near-perfect fidelity: male hypogonadism.
The overlap between hypogonadism and mood disorders is not merely incidental. The Endocrine Society’s guidelines explicitly list the non-specific signs of low testosterone—fatigue, depressed mood, irritability, and diminished well-being—as indistinguishable from those of mood and anxiety disorders typically treated in outpatient psychiatric settings. For the clinician who treats the symptom without interrogating its source, the consequences can range from prolonged suffering to treatment resistance to missed diagnoses of serious underlying pathology. This article provides a framework for understanding, diagnosing, documenting, and coordinating care for men with testosterone deficiency, with an emphasis on the psychiatric interface and the clinical reasoning that must underpin every diagnostic code.
The Clinical Chameleon – How Hypogonadism Masquerades as Psychiatric Illness
The clinical manifestations of testosterone deficiency are diverse and span multiple domains. According to the Endocrine Society’s clinical practice guidelines, symptoms include reduced libido (considered the principal correlate of low testosterone), erectile dysfunction (often multifactorial), decreased muscle mass and strength, increased fat mass, low bone density, fatigue, and mood disturbances. These symptoms collectively contribute to impaired quality of life.
The non-specific signs and symptoms of hypogonadism—fatigue, depressed mood, irritability, diminished well-being—are indistinguishable from those of mood and anxiety disorders. This is not a peripheral observation; it is a core diagnostic challenge. A man presenting with anhedonia, social withdrawal, and loss of motivation could be suffering from major depression, testosterone deficiency, or both. The treating clinician cannot rely on symptom pattern alone to differentiate.
Adding to the complexity, the relationship between testosterone and mood is bidirectional. Low testosterone can cause or worsen anxiety and depression symptoms, including irritability, persistent sadness, lack of motivation, social withdrawal, and others. Low T also causes physical changes, such as decreases in muscle mass and strength, sudden weight gain, increased breast tissue, and erectile dysfunction. These physical symptoms can themselves cause a loss of confidence and self-esteem that intensifies anxiety and depression symptoms, creating a self-perpetuating cycle.
Epidemiological studies, including the European Male Ageing Study, report that 20–30 percent of men aged 50 years and older present serum testosterone concentrations below commonly applied reference ranges. However, such findings vary depending on the study population and diagnostic criteria, and do not by themselves establish hypogonadism.
For the mental health clinician, the critical question is not whether low testosterone can cause depressive symptoms—the evidence is clear that it can—but rather, how to distinguish primary depression from secondary depression and how to document that distinction in a way that justifies appropriate treatment, supports medical necessity, and protects against audit risk.
The Neurobiological Connection – Why Testosterone Matters in Mental Health
Testosterone plays a pivotal role in maintaining balance within the multi-dimensional psychological network of mood, behaviour, self-perception, and perceived quality of life in men of any age. Beyond classical forms of hypogonadism, low testosterone concentrations can also be seen in older men, described as an age- and comorbidity-driven functional hypogonadism, and might relate to depressive symptoms exhibiting a wide array of clinical pictures ranging from dysthymia and fatigue to inertia, listlessness, hopelessness, and suicidal thoughts.
The steroid modulates the stress response, threat vigilance, and reward processing, influencing both pro-active and reactive dimensions of aggression, assertiveness, and social behaviour. Correspondingly, anxiolysis is likely to be modulated by testosterone via stress resilience, threat vigilance, and reward processing.
The neurobiological mechanisms underlying these effects are well-established. Testosterone influences the serotonergic, dopaminergic, and noradrenergic systems—the very neurotransmitter pathways targeted by standard antidepressant medications. Androgen receptors are widely distributed in brain regions implicated in mood regulation, including the amygdala, hippocampus, and prefrontal cortex. When testosterone levels fall, the functional integrity of these circuits may be compromised, producing a clinical picture that mirrors endogenous depression.
Critically, a 2025 study found that bioavailable testosterone (but not total testosterone) levels and depression scores in elderly men show a significant inverse correlation, independent of age and weight. This underscores the importance of measuring free or bioavailable testosterone, not merely total testosterone, when assessing the hormonal contribution to mood symptoms.
The Diagnostic Architecture – Primary vs. Secondary Hypogonadism
The ICD-10-CM coding framework distinguishes where the defect lies along the hypothalamic-pituitary-testicular axis. The choice of code is not merely an administrative detail; it reflects the underlying pathophysiology and guides treatment decisions. Understanding this architecture is essential for accurate documentation and appropriate referral.
Primary Hypogonadism (Testicular Failure)
Primary hypogonadism originates in the testes themselves. The testicles fail to produce adequate testosterone despite adequate stimulation from the pituitary. Laboratory confirmation typically shows low total testosterone with elevated luteinizing hormone (LH) and follicle-stimulating hormone (FSH)—the pituitary is working overtime to compensate. The correct ICD-10 code is E29.1 (Testicular hypofunction).
The American Urological Association recommends using ICD-10 code E29.1 as the primary diagnostic code when clinical suspicion of testosterone deficiency exists based on symptoms or risk factors, such as reduced energy, reduced endurance, diminished work or physical performance, fatigue, depression, reduced motivation, poor concentration, impaired memory, irritability, reduced sex drive, or erectile dysfunction. The AUA also suggests considering physical signs, such as changes in body habitus, reduced virilization, gynecomastia, or testicular abnormalities, when selecting E29.1.
High-risk conditions that should prompt consideration of E29.1 even in the absence of symptoms include unexplained anemia, bone density loss, diabetes, chemotherapy exposure, testicular radiation exposure, HIV/AIDS, chronic narcotic use, male infertility, pituitary dysfunction, or chronic corticosteroid use.
Secondary Hypogonadism (Pituitary or Hypothalamic Dysfunction)
Secondary hypogonadism arises from failure of the pituitary or hypothalamus. The laboratory pattern shows low total testosterone with inappropriately low or normal LH and FSH—the pituitary is not sending the necessary signals. The correct ICD-10 code is E23.0 (Hypopituitarism). This code also captures Kallmann syndrome, isolated gonadotropin deficiency, and pituitary insufficiency from tumours, infiltrative diseases, or head trauma.
Despite the division of hypogonadism into primary and secondary causes, a mixed picture is often seen in older men and individuals with diabetes mellitus. In the latter, this is believed to be because of the cytokine response seen in diabetes and its effects on the gonadotropin-releasing hormone (GnRH) pulse generator.
Postprocedural Hypogonadism
When hypogonadism follows a medical procedure such as bilateral orchidectomy, pelvic radiation, or chemotherapy, the appropriate code is E89.5 (Postprocedural testicular hypofunction). For patients with a history of testicular cancer or childhood leukaemia who now present with depressive symptoms, this code may be correct.
The Evidence Base – Testosterone Replacement Therapy and Depression
The evidence that testosterone therapy can alleviate depressive symptoms in hypogonadal men has grown substantially over the past two decades. The question for the mental health clinician is not whether TRT works, but for whom, under what conditions, and in what relationship to standard psychiatric treatment.
A 2019 systematic review and meta-analysis of 27 randomized controlled trials including 1,890 men found that testosterone treatment was associated with a significant reduction in depressive symptoms compared with placebo (Hedges g, 0.21; 95% CI, 0.10–0.32), showing an efficacy of odds ratio of 2.30 (95% CI, 1.30–4.06). Testosterone treatment appeared to be effective and efficacious in reducing depressive symptoms in men, particularly when higher-dosage regimens were applied in carefully selected samples. However, the authors noted that given the heterogeneity of the included RCTs, more preregistered trials are needed that explicitly examine depression as the primary end point.
Meta‑regression models suggested significant interactions for testosterone treatment with dosage and symptom variability at baseline. In the most conservative bias scenario, testosterone treatment remained significant whenever dosages greater than 0.5 g per week were administered and symptom variability was kept low.
An earlier meta-analysis of seven studies (N=364) showed a significant positive effect of TT therapy on HAM-D response in depressed patients when compared with placebo. Subgroup analysis also showed a significant response in the subpopulations with hypogonadism and HIV/AIDS, as well as in patients treated with TT gel. The route by which TT is administered may play a role in treatment response.
A 2025 narrative review of TRT in men aged 50 and above concluded that TRT consistently improved sexual desire, erectile function, lean body mass, bone mineral density, insulin sensitivity, and vitality, with most benefits observed in men with baseline testosterone levels less than 300 ng/dL and target levels maintained at 500–800 ng/dL.
However, the clinical nuance remains critical. TRT is not a replacement for antidepressant medication or psychotherapy in men who meet full DSM‑5 criteria for major depressive disorder. For patients with severe depressive symptoms, the appropriate treatment is standard psychiatric care, with TRT considered as an adjunct if hypogonadism is confirmed and the depressive episode is refractory or if the contribution of hypogonadism to the mood disturbance is judged to be substantial.
Cognitive Effects – What the Research Shows
The cognitive implications of testosterone deficiency and its replacement are directly relevant to the mental health clinician, as cognitive complaints—poor concentration, memory impairment, “brain fog”—are among the most common presenting symptoms in psychiatric practice.
A long-term TRT could improve specific cognitive functions, such as verbal and spatial memory, cognitive flexibility, and physical vitality. However, randomized controlled trials do not provide positive results, and in most of the cases TRT might not induce beneficial effects on cognitive function in elderly men.
The evidence is mixed. Some studies have found improvements in cognition in hypogonadal men receiving testosterone supplementation, including visuospatial ability, verbal fluency, perceptual speed, and verbal memory prior to and following T supplementation. Other studies have found no significant improvement in visual memory, executive function, or spatial ability based on a battery of well-chosen tests.
For the clinician, the implication is that cognitive complaints in a hypogonadal man may improve with TRT, but they should not be expected to do so. Comprehensive psychiatric assessment and treatment of any underlying cognitive disorder should proceed in parallel.
Ancillary Codes and Documentation Strategy
The accurate coding of testosterone deficiency requires more than the selection of a primary ICD-10 code. Ancillary codes capture the clinical context, justify medical necessity, and support appropriate reimbursement.
The AUA recommends using supplementary codes when specific symptoms are prominent:
N52.9 (Male erectile dysfunction, unspecified) if erectile dysfunction is the primary complaint.
R53.83 (Other fatigue) if fatigue is the presenting symptom.
F32.9 (Major depressive disorder, single episode, unspecified) if depressive symptoms are prominent.
D64.9 (Anemia, unspecified) if unexplained anemia is present.
For patients receiving long-term TRT, the encounter code Z79.890 (Hormone replacement therapy) should be added as a secondary code to indicate that the patient is on ongoing hormonal treatment. This code is not used for a single injection or a brief trial but for established, continuing therapy.
Documentation requirements for E29.1 (Testicular hypofunction) :
The clinical validation of E29.1 requires documentation of at least two morning total testosterone levels below 300 ng/dL, along with elevated LH and FSH levels for primary hypogonadism. The documentation must include specific symptoms, such as erectile dysfunction, fatigue, depressed mood, or reduced libido. Ensure documentation includes specific lab values and physical exam findings, and avoid confusion with secondary hypogonadism (E23.0).
Documentation requirements for E23.0 (Hypopituitarism) :
For secondary hypogonadism, the record must document low testosterone with low or normal LH and FSH, along with MRI evidence of pituitary lesion where available. Document pituitary dysfunction and related lab results clearly.
Documentation requirements for E89.5 (Postprocedural testicular hypofunction) :
The record must clearly link the hypogonadism to a specific surgical or procedural history, including the date and nature of the procedure.
Clinical Scenarios in Psychiatric Practice
Scenario 1: The Patient Already on Antidepressants
A 45-year-old man with a diagnosis of major depressive disorder has been on two SSRIs over 18 months with partial response. He reports persistent fatigue, diminished libido, and anhedonia. PHQ-9 remains 16. He has never been screened for hypogonadism.
In this case, the clinician should order morning total and free testosterone, LH, and FSH. If low testosterone is confirmed, the patient should be referred to endocrinology or primary care for evaluation. The psychiatric diagnosis remains primary, with the hypogonadism code secondary. The documentation should explicitly state the clinical reasoning: “Patient’s depressive symptoms have been partially treatment-resistant; rule out hypogonadism as a contributing factor.”
Scenario 2: The Patient with Mild, Subsyndromal Symptoms
A 52-year-old man presents with fatigue, irritability, and reduced motivation but does not meet full DSM‑5 criteria for a major depressive episode. Laboratory testing reveals low testosterone with elevated LH.
In this case, the primary diagnosis is E29.1 (Testicular hypofunction). The psychiatric symptom code (e.g., R53.83 for fatigue) may be used as a secondary code. The patient may be treated with TRT without concurrent antidepressant medication.
Scenario 3: The Patient on TRT with Persistent Mood Symptoms
A 60-year-old man with confirmed hypogonadism has been on TRT for six months with normalization of testosterone levels. He continues to report depressed mood and anhedonia and meets full criteria for major depressive disorder.
Here, the primary diagnosis is F32.9 or F33.9, with E29.1 as a secondary code and Z79.890 to indicate ongoing hormone replacement therapy. The depression is not solely attributable to the hypogonadism and requires independent psychiatric treatment.
Safety and Monitoring – What the Prescribing Clinician Must Know
For mental health clinicians who collaborate with prescribing physicians, understanding the risks and monitoring requirements of TRT is essential for comprehensive patient care.
Testosterone replacement therapy is a well-tolerated and established treatment for hypogonadism, providing excellent clinical and biochemical relief from the effects of sex steroid deficiency. However, possible adverse effects include increased estrogen levels and gynecomastia, which are usually managed with aromatase inhibitors and tamoxifen. Cardiovascular risks from TRT include hypertension and erythrocytosis, which mandate periodic hematocrit and blood pressure monitoring; therapeutic phlebotomy is indicated if the hematocrit exceeds 52 percent.
Safety data indicate no increased risk of major adverse cardiovascular events or prostate cancer when guidelines are followed, though erythrocytosis remains the most common dose-related adverse effect. TRT should not be administered to individuals with active evidence of untreated prostate cancer, except under rare circumstances such as active surveillance for very low-risk disease.
Monitoring should be performed in the steady state after at least four doses. Serum testosterone should be maintained within the physiological range by adjusting the dose of the preparation being used.
FAQ
What is the difference between E29.1 and E23.0 for low testosterone?
E29.1 (Testicular hypofunction) is used for primary hypogonadism, where the problem originates in the testes themselves. Laboratory findings show low total testosterone with elevated LH and FSH. E23.0 (Hypopituitarism) is used for secondary hypogonadism, where the pituitary fails to send signals to the testes, resulting in low testosterone with low or normal LH and FSH. The distinction has important treatment implications.
Do I need a low testosterone level documented to assign E29.1?
Yes. E29.1 is a billable code that requires clinical validation. The documentation must include at least two fasting morning total testosterone levels less than 300 ng/dL and, to confirm primary hypogonadism, elevated LH and FSH levels. A diagnosis of hypogonadism cannot be made on symptoms alone.
Can I assign a depressive disorder code and a hypogonadism code together?
Yes. When a patient meets full DSM‑5 criteria for a major depressive episode and also has confirmed hypogonadism, both codes should be assigned. The primary code should reflect the reason for the encounter. If the patient is being treated primarily for depression, sequence the psychiatric code first. If the hypogonadism is the primary focus, sequence E29.1 or E23.0 first.
What documentation is required to support testosterone level testing in a patient with depression?
The medical record must explicitly state the clinical reason for ordering the test. This should include a description of the symptoms that prompted suspicion of hypogonadism. Example: “Patient reports persistent fatigue, diminished libido, and anhedonia despite two trials of antidepressant medication. Rule out hypogonadism as a contributing factor.” Without such documentation, a payer may deny coverage for the laboratory testing.
What is the role of the mental health clinician in managing a patient on TRT?
The mental health clinician’s role is to monitor mood symptoms, assess for any worsening of depression or emergence of irritability or aggression, ensure adherence to psychiatric treatment, and communicate with the prescribing physician about any changes in mental status. While TRT may improve mood, it is not a substitute for evidence-based psychiatric treatment when a depressive disorder is present.
References
Praxismed. (2025). Testosterone Deficiency Diagnosis and Coding.
ICDcodes.ai. (2025). Male Hypogonadism – ICD-10 Documentation Guidelines.
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Not medical advice. For informational use only.
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