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Anabolic Steroids StatPearls NCBI Bookshelf
Anabolic Steroids: Pharmacology, Clinical Use, and Safety Considerations
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1. What is the mechanism of action for anabolic steroids?
Step Mechanism Result
1. Cellular uptake Lipophilic steroid enters cell via passive diffusion or carrier‑mediated transport. Steroid reaches cytoplasm.
2. Nuclear binding Dissociates from heat‑shock protein complexes → binds directly to the intracellular androgen receptor (AR). AR–steroid complex forms.
3. DNA transcription Complex translocates to nucleus, attaches to androgen response elements (AREs) on target gene promoters. Recruitment of co‑activators (p300/CBP), histone acetyltransferases → chromatin remodeling.
4. Gene expression Initiation of mRNA synthesis for anabolic proteins: IGF‑1, myosin heavy chain, creatine kinase, etc.; suppression of pro‑catabolic genes (myostatin). Protein translation → muscle hypertrophy.
5. Systemic effects Upregulation of glucose transporter type 4 (GLUT4) → insulin‑like sensitivity; increased testosterone synthesis via HMG‑CoA reductase activation, aromatization to estradiol for bone health; stimulation of erythropoiesis via EPO up‑regulation. Enhanced oxygen delivery and performance.
Key points
Anabolic signaling: Testosterone binds androgen receptors → dimerizes with DNA → transcriptional activation.
Protein synthesis vs degradation balance: ↑S6K1, ↑mTORC1; ↓FoxO3a activity; ↓Atrogin‑1/MAFbx expression.
Metabolic shift: Increased glycogen storage and lipid oxidation in muscle fibers.
2. How anabolic steroids affect the male reproductive system
Effect Mechanism Clinical consequence
Suppressed spermatogenesis Exogenous testosterone > LH/FSH → negative feedback on pituitary → ↓LH, ↓FSH. Sertoli cells need FSH; Leydig cells need LH for endogenous testosterone production. Oligo‑ or azoospermia; reduced sperm count and motility.
Testicular atrophy Loss of intratesticular hormone production (no testosterone from Leydig cells) → shrinkage of seminiferous tubules. Reduced testicular volume, infertility.
Gynecomastia Aromatization of excess testosterone to estrogen in adipose tissue. Estrogen binds ERα → stimulates breast tissue proliferation. Breast tenderness, enlargement.
Reduced libido & erectile dysfunction Low endogenous testosterone; altered androgen receptor signaling; possible increased prolactin (due to hypothalamic-pituitary changes). Decreased sexual desire, impaired erection.
Sleep apnea exacerbation Hormonal changes affect airway muscle tone; weight gain from anabolic steroid use increases fat deposition around neck. More frequent apneic events, worsened oxygen desaturation.
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3. Differential Diagnosis
Clinical Feature Possible Condition Rationale
Breast enlargement (painless) Gynecomastia secondary to anabolic steroid use; hyperthyroidism; liver disease Steroids increase aromatase → estrogen ↑; thyrotoxicosis causes breast edema
Fatigue, weakness Hypothyroidism (primary or central), anemia, chronic kidney disease TSH low/normal with high fT4 suggests secondary hypothyroid or thyrotoxic periodic paralysis
Palpitations / tachycardia Thyrotoxicosis, anxiety, electrolyte imbalance Thyroid hormone excess → increased HR; hypokalemia also causes palpitations
Weight gain Hypothyroidism (central), glucocorticoid therapy, lifestyle Central hypothyroidism leads to metabolic slowdown
Sleep disturbance / insomnia Anxiety, caffeine intake, thyroid hormone excess Elevated T4 can disrupt sleep patterns
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2. Differential Diagnoses
Condition Supporting Features Opposing Features
Central (hypothalamic/pituitary) hypothyroidism Low FT4, normal/low TSH, low IGF‑1, low LH/FSH, weight gain, fatigue, cold intolerance. None; fits all findings.
Primary (T3/T4) hypothyroidism Usually elevated TSH. TSH is normal.
Secondary pituitary failure Low IGF‑1, low gonadotropins. TSH and FT4 are within reference range.
Syndrome X (hypogonadotropic hypogonadism) Low LH/FSH with normal or slightly elevated prolactin. Fits.
Pituitary adenoma Elevated prolactin, mass effect. No visual field deficits; prolactin only mildly increased.
Hypothalamic dysfunction Low GnRH leading to low gonadotropins. Possible.
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4. Differential Diagnosis
Category Specific Conditions Key Features / Rationale
Endocrine Causes Hypogonadotropic hypogonadism (Sertoli‑cell dysfunction) Low LH/FSH; low testosterone; normal prolactin; no visual field loss.
Idiopathic hypogonadotropic hypogonadism Usually normal pituitary imaging; may have delayed puberty in males.
Hypothalamic disease (e.g., infiltrative, glioma) Low gonadotropins; possible other pituitary hormone deficits or neuro symptoms.
Primary testicular failure Would present with high LH/FSH, not low.
Neurological Causes Pituitary adenoma causing hypopituitarism Visual field loss is typical but can be mild or absent early on.
Craniopharyngioma Often presents in children, visual deficits common.
Hydrocephalus, meningitis, trauma Could compress pituitary or hypothalamus, affecting hormone release.
Endocrine Disruptors Thyroid disorders, adrenal insufficiency (secondary) Might cause low LH/FSH but with other hormonal changes.
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5. How the Two Findings Interrelate
Hypothalamic‑Pituitary Axis:
The hypothalamus secretes gonadotropin‑releasing hormone (GnRH), which drives pituitary secretion of LH and FSH. Any structural or functional lesion affecting the hypothalamus, pituitary stalk, or anterior lobe can disrupt GnRH release and consequently lower LH/FSH.
Visual Pathway Involvement:
The optic chiasm is anatomically adjacent to the pituitary stalk. Tumors (e.g., craniopharyngioma, pituitary adenoma), inflammatory processes, or ischemia in this area can compress both visual pathways and the pituitary stalk, explaining simultaneous visual deficits and endocrine dysfunction.
Differential Diagnoses:
- Pituitary Adenoma: Often compresses optic chiasm → bitemporal hemianopsia; can cause hypopituitarism.
- Craniopharyngioma: Benign but tends to involve optic pathways and pituitary stalk.
- Hypothalamic–pituitary Apoplexy: Sudden hemorrhage/ischemia → visual changes + endocrine crisis.
- Inflammatory Disorders (e.g., Lymphocytic Hypophysitis): May affect stalk & chiasm.
- Neurohypophyseal Arteriovenous Malformations: Rare, but can produce similar symptoms.
Thus the clinical picture strongly suggests a lesion at or near the optic chiasm/pituitary region that also involves the pituitary stalk—most commonly a pituitary macroadenoma, especially if it is invasive. Imaging (MRI) and endocrine evaluation would confirm the diagnosis.
Answer: The combined visual disturbance of bitemporal hemianopia with a pituitary stalk‑related headache points to a compressive lesion at the optic chiasm that also involves or displaces the pituitary stalk—most often a large, invasive pituitary macroadenoma (or similarly sized sellar mass).
Gender: Female