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Androstenedione (A4)
Reproductive
Report in 48Hrs
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No Fasting Required
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Evaluate causes of excess androgens for Hormonal imbalance assessment
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Androstenedione (A4) - Comprehensive Medical Test Information Guide
- Why is it done?
- Test Purpose: Androstenedione (A4) is a weak androgen hormone produced by the adrenal glands and ovaries. This blood test measures the level of androstenedione to evaluate adrenal function, hormonal imbalances, and reproductive disorders. A4 serves as a precursor to both testosterone and estrogen production.
- Primary Indications for Testing: Suspected adrenal insufficiency or adrenal hyperplasia; evaluation of virilization or hirsutism in women; assessment of polycystic ovary syndrome (PCOS); investigation of infertility; evaluation of abnormal pubertal development; monitoring of adrenal hormone disorders; assessment of amenorrhea or irregular menses; evaluation of virilizing tumors; monitoring of congenital adrenal hyperplasia (CAH) treatment.
- Timing and Clinical Circumstances: Testing is typically performed in the morning when A4 levels are highest; may be ordered during initial diagnosis of hormonal disorders or as part of routine monitoring; often performed in conjunction with other hormone measurements (ACTH, cortisol, testosterone); can be used for follow-up evaluation of treated conditions; commonly ordered when patients present with symptoms of androgen excess or adrenal dysfunction.
- Normal Range
- Reference Range Values: Adult Males: 75-205 ng/dL (2.6-7.2 nmol/L); Adult Females (Follicular Phase): 60-110 ng/dL (2.1-3.8 nmol/L); Adult Females (Luteal Phase): 90-275 ng/dL (3.1-9.6 nmol/L); Children: Values vary significantly by age and pubertal stage; reference ranges differ between laboratories and measurement methods.
- Units of Measurement: Nanograms per deciliter (ng/dL) or nanomoles per liter (nmol/L); conversion factor: 1 ng/dL = 0.0349 nmol/L.
- Interpretation of Results: Normal Result: Androstenedione levels within the reference range suggest normal adrenal and gonadal function with appropriate hormone production; Elevated Result (High): Values above the upper limit of normal may indicate adrenal hyperplasia, adrenal tumors, PCOS, ovarian tumors, or other conditions causing androgen excess; Low Result: Values below the lower limit of normal may suggest adrenal insufficiency, hypopituitarism, or other conditions affecting adrenal hormone production; Borderline Values: Results near the upper or lower limits require clinical correlation with symptoms and other hormone measurements for accurate interpretation.
- What Normal vs. Abnormal Means: Normal values typically indicate that the adrenal glands and ovaries/testes are functioning appropriately and producing appropriate amounts of androstenedione. Abnormal values suggest a disruption in the hypothalamic-pituitary-adrenal (HPA) axis or gonadal function, requiring further investigation to determine the underlying cause and appropriate treatment.
- Interpretation
- Elevated Androstenedione Results: Indicates increased androgen production; may suggest congenital adrenal hyperplasia (CAH), particularly 21-hydroxylase deficiency; can indicate polycystic ovary syndrome (PCOS), especially when elevated in conjunction with testosterone; may suggest adrenal adenoma or carcinoma; can indicate ovarian androgen-secreting tumors; associated with conditions causing virilization or hirsutism; often seen in ectopic ACTH syndrome.
- Low Androstenedione Results: Suggests inadequate adrenal hormone production; may indicate primary adrenal insufficiency (Addison's disease); can suggest secondary adrenal insufficiency due to pituitary or hypothalamic disorders; may indicate hypopituitarism; can be seen following adrenal surgery or radiation; associated with severe illness or sepsis; may reflect inappropriate glucocorticoid replacement therapy.
- Factors Affecting Androstenedione Levels: Circadian rhythm (higher in morning, lower in evening); menstrual cycle phase in women (varies throughout cycle); age and pubertal development stage; pregnancy (levels may be altered); medications (corticosteroids, estrogens, anticonvulsants); obesity; stress levels; underlying systemic illness; time of day specimen was collected; laboratory methodology and assay variability.
- Clinical Significance of Result Patterns: Markedly elevated A4 with elevated 17-hydroxyprogesterone suggests CAH; elevated A4 with normal or low cortisol and elevated ACTH indicates primary adrenal insufficiency; elevated A4 with suppressed ACTH suggests autonomous adrenal tumor; elevated A4 in woman with menstrual irregularities and hirsutism is characteristic of PCOS; serial A4 measurements help monitor response to treatment; trends in A4 levels are often more clinically useful than isolated values; comparison with other adrenal hormones (cortisol, ACTH, 17-hydroxyprogesterone) provides diagnostic clarity.
- Associated Organs
- Primary Organ Systems Involved: Adrenal Glands: Primary source of androstenedione production; adrenal cortex produces approximately 50% of circulating A4; responsible for the zona reticularis hormone production; Ovaries: Significant source of androstenedione in women; increased production by ovarian theca cells, particularly in PCOS; Testes: Minimal contribution to circulating androstenedione in men; primarily produces testosterone; Pituitary Gland: Regulates adrenal and gonadal function via ACTH and gonadotropins; abnormalities affect A4 production; Hypothalamus: Controls pituitary function through hormonal signaling affecting A4 levels.
- Diseases and Conditions Associated with Abnormal Results: Congenital Adrenal Hyperplasia (CAH): Most common cause of elevated A4; 21-hydroxylase deficiency accounts for 90% of cases; 11β-hydroxylase deficiency also causes elevation; 3β-hydroxysteroid dehydrogenase deficiency results in increased A4; Polycystic Ovary Syndrome (PCOS): Elevated androstenedione common finding; associated with irregular menses, hirsutism, and infertility; Adrenal Insufficiency: Primary (Addison's disease) and secondary forms result in low A4; may be autoimmune, infectious, or due to pituitary dysfunction; Adrenal Tumors: Adrenal adenomas and carcinomas can produce excess A4; adrenocortical carcinoma typically causes marked elevation; Ovarian Tumors: Androgen-secreting ovarian tumors (arrhenoblastomas, granulosa cell tumors) cause elevated A4; Cushing's Syndrome: ACTH-secreting tumors may be associated with elevated A4; ectopic ACTH production can increase A4 levels; Hypopituitarism: Decreased ACTH leads to low adrenal hormone production including A4; Hypothyroidism: Can affect adrenal hormone metabolism and A4 levels; Obesity: Associated with elevated androstenedione due to metabolic effects; Infertility: Both male and female infertility may be associated with abnormal A4 levels.
- Complications and Risks Associated with Abnormal Results: Elevated Androstenedione Complications: Virilization in women (male pattern baldness, clitoral enlargement, acne); hirsutism (excessive hair growth); menstrual irregularities and infertility; increased cardiovascular risk; metabolic syndrome; increased risk of diabetes; endometrial hyperplasia from unopposed estrogen effects; psychological distress from virilization symptoms; Low Androstenedione Complications: Fatigue and weakness; hypotension (low blood pressure); hypoglycemia risk; loss of secondary sexual characteristics; infertility; increased infection risk; salt wasting in severe cases; cardiovascular collapse if acute adrenal crisis occurs; decreased bone mineral density with chronic insufficiency.
- Follow-up Tests
- Additional Tests for Elevated Androstenedione: 17-Hydroxyprogesterone: Essential to diagnose 21-hydroxylase deficiency CAH; helps differentiate CAH from other causes of A4 elevation; Totally Free and Bioavailable Testosterone: Confirm androgen excess; assess degree of virilization risk; ACTH (Adrenocorticotropic Hormone): Helps determine if elevation is adrenal or gonadal in origin; elevated ACTH with elevated A4 suggests adrenal cause; Cortisol (Morning and Evening or 24-hour Urine): Assess overall adrenal function; identify patterns of adrenal dysfunction; Dexamethasone Suppression Test: Determine if elevated A4 is ACTH-dependent or independent; help identify autonomous tumors; Prolactin Level: Often measured alongside A4 if menstrual abnormalities present; Fasting Insulin and Glucose: Assess metabolic syndrome risk, particularly in PCOS; Lipid Panel: Evaluate cardiovascular risk profile; Thyroid Function Tests (TSH, Free T4): Rule out thyroid dysfunction contributing to hormonal abnormalities; Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH): Evaluate gonadal function and reproductive axis; Estradiol: Assess overall estrogen status; Pelvic Ultrasound: If PCOS or ovarian tumor suspected; visualize ovarian morphology; Adrenal Imaging (CT or MRI): If adrenal tumor suspected; confirm tumor presence and assess size/characteristics; Ovarian/Testicular Ultrasound: If gonadal tumor suspected.
- Additional Tests for Low Androstenedione: Cortisol (8 AM Serum): Assess adrenal insufficiency severity; low cortisol with low A4 suggests primary adrenal failure; ACTH Level: Elevated ACTH with low cortisol confirms primary adrenal insufficiency; normal or low ACTH with low cortisol suggests secondary insufficiency; TSH and Free T4: Rule out hypothyroidism; thyroid dysfunction can contribute to adrenal dysfunction; Growth Hormone and IGF-1: If pituitary dysfunction suspected; FSH and LH: Evaluate gonadotropin-releasing hormone (GnRH) axis; 24-Hour Urine Free Cortisol: Confirm adrenal insufficiency diagnosis; ACTH Stimulation Test: Determine adrenal gland responsiveness; differentiate primary from secondary insufficiency; Insulin-Induced Hypoglycemia Test: Assess pituitary-adrenal axis if secondary insufficiency suspected; Adrenal Imaging (CT or MRI): If adrenal pathology suspected; rule out adrenal metastases, hemorrhage, or infiltration; Pituitary MRI: If secondary insufficiency indicated; evaluate pituitary structure and function; Autoimmune Markers: If Addison's disease suspected; screen for adrenal antibodies.
- Monitoring Frequency for Ongoing Conditions: Congenital Adrenal Hyperplasia: Baseline A4 and 17-OHP established at diagnosis; monitoring every 6-12 months during childhood; annual monitoring in adolescents and adults; more frequent monitoring (every 3 months) during treatment adjustment or dose changes; A4 used to assess adequacy of glucocorticoid and mineralocorticoid replacement; Polycystic Ovary Syndrome: Initial A4 measurement; repeat annually or every 6-12 months if monitoring response to treatment; regular monitoring if on medications affecting hormone levels; Adrenal Insufficiency: A4 measured at diagnosis and during treatment initiation; monitored during dose adjustments of replacement therapy; periodic measurement (annually) during maintenance therapy; more frequent monitoring if symptoms suggest inadequate replacement; Adrenal Tumors: Serial A4 measurement to track tumor progression; measurements before and after surgical intervention; periodic surveillance if tumor managed conservatively; Infertility Evaluation: Single measurement or serial measurements during investigation of cause; follow-up testing as appropriate based on diagnosis.
- Related Tests Providing Complementary Information: Complete Adrenal Hormone Panel: Cortisol, ACTH, 17-hydroxyprogesterone, and A4 together provide comprehensive adrenal assessment; Androgen Profile: Testosterone, free testosterone, DHEA-S alongside A4 for complete androgen evaluation; Reproductive Hormone Panel: FSH, LH, estradiol, progesterone with A4 for fertility assessment; Metabolic Panel: Glucose, lipids, insulin for comprehensive metabolic evaluation alongside hormone assessment; Autoimmune Screening: Adrenal peroxidase antibodies (21-hydroxylase antibodies) if autoimmune adrenal insufficiency suspected; Tumor Markers: Alpha-fetoprotein, HCG if adrenocortical carcinoma or germ cell tumors suspected.
- Fasting Required?
- Fasting Requirement: No - Fasting is NOT required for androstenedione measurement. This is a non-fasting test that can be performed at any time during the day, regardless of meal intake.
- Optimal Timing: Early morning collection (7-9 AM) is preferred because androstenedione follows a circadian rhythm with highest levels in the early morning; results are most clinically meaningful when collected at the same time as previous specimens for comparison; testing between 8-10 AM is standard practice for hormone measurement; avoid late afternoon or evening collection when possible due to naturally lower levels.
- Medications to Avoid: Discuss all current medications with the healthcare provider before testing as certain medications can affect A4 levels; corticosteroids (dexamethasone, prednisone) suppress A4 and should be discussed with the physician; estrogen-containing oral contraceptives may affect results (note usage before test); spironolactone may affect hormone measurements; some anticonvulsants (phenytoin) can alter hormone metabolism; arrange testing timing relative to medication dosing when possible; do NOT discontinue prescribed medications without physician guidance; inform laboratory of all medications being taken.
- General Patient Preparation Requirements: Arrive early morning (7-9 AM preferred) for optimal hormone measurement; inform phlebotomist of current medications and supplements; no special clothing required, but wear loose-fitting clothing to facilitate blood draw; note menstrual cycle phase if female, as A4 varies throughout the cycle; avoid strenuous exercise 24 hours before testing if possible; stress should be minimized before testing as acute stress can affect cortisol and potentially A4 levels; drink adequate fluids the night before to ensure good hydration for easier blood draw; normal diet is acceptable and consumed normally; use bathroom before blood draw to reduce patient stress; For Serial Testing: Keep appointment time consistent (preferably same time of day) to minimize circadian rhythm effects; perform all follow-up tests at same time interval as baseline for meaningful comparison; maintain same day-of-cycle for women when possible if serial testing during different cycles; Special Circumstances: Inform healthcare provider if significantly stressed or ill, as this may affect results; note if taking any new medications since last test; provide information about any recent illness, surgery, or major life stressors.
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