Laurence Shockey
|Subscribers
About
Nandrolone: Uses, Benefits & Side Effects
# Nandrolone – A Comprehensive Overview
> *"Nandrolone is an anabolic–androgenic steroid (AAS) originally developed to treat various medical conditions that involve loss of muscle mass, anemia, and bone density loss."*
> — **American Association for the Study of Liver Diseases**
---
## 1. What Is Nandrolone?
| Feature | Detail |
|---------|--------|
| **Full name** | 19‑(2E)-3-(4‑hydroxy‑2‑methoxy‑5‑methylphenyl)prop-2‑enyl‑2,4‑diene‑1‑ol |
| **Common names** | Testosterone decanoate (Deca‑D), Nandrolone decanoate |
| **Drug class** | Anabolic–androgenic steroid (AAS) |
| **Route of administration** | Intramuscular injection (usually once every 2–4 weeks) |
| **Legal status** | Prescription only in most countries; controlled substance |
---
## 3. Pharmacology
### 3.1 Mechanism of Action
- **Androgen receptor activation:** After intramuscular injection, the esterified testosterone is slowly hydrolyzed by plasma esterases to free testosterone (and its metabolites). Testosterone binds to intracellular androgen receptors (AR) in target tissues (muscle, bone, liver, etc.).
- **Gene transcription:** The AR–testosterone complex translocates to the nucleus and activates transcription of genes involved in protein synthesis, cell proliferation, and nitrogen retention.
### 3.2 Pharmacokinetics
| Parameter | Typical Value |
|-----------|---------------|
| Absorption rate (t₁/₂ absorption) | ~10–14 days for testosterone enanthate at 250 mg/mL (due to depot injection). |
| Peak plasma concentration | Reaches a maximum within 2–3 weeks after injection. |
| Elimination half‑life | ~4–5 days once the drug is in systemic circulation. |
| Total duration of effect | ~6–8 weeks per dose; cumulative effects last longer due to protein synthesis and muscle memory. |
### 3.3 Clinical Uses
- **Hormone replacement therapy** for men with hypogonadism.
- Treatment of delayed puberty, low libido, infertility related to low testosterone.
- Adjunct in anabolic‑androgenic steroid protocols for athletes seeking increased lean mass, strength, and recovery.
---
## 4. How Testosterone Works
### 4.1 Hormonal Signaling
| Step | Process |
|------|---------|
| **Synthesis** | Leydig cells (testes) produce testosterone from cholesterol under LH stimulation. |
| **Release & Transport** | Circulates in blood bound to SHBG or albumin; only free/unbound fraction is biologically active. |
| **Cellular Entry** | Testosterone diffuses across cell membranes into target tissues. |
| **Receptor Binding** | Binds androgen receptors (AR) in cytoplasm, forming a hormone‑receptor complex. |
| **Nuclear Translocation** | Complex moves to nucleus and binds DNA at androgen response elements. |
| **Transcriptional Activation** | Modulates gene expression: upregulation of proteins for protein synthesis, glycogen synthesis, enzyme activity, etc. |
---
## 3. Muscular Effects of Testosterone
| Effect | Mechanism & Supporting Evidence |
|--------|--------------------------------|
| **Increased Myofibrillar Protein Synthesis (MPS)** | AR‑mediated transcription upregulates genes encoding ribosomal proteins and translation factors. Studies in rodents show ~50% increase in MPS after acute testosterone administration; human trials report a 15–25% rise in basal MPS (Cermak et al., 2016). |
| **Reduced Protein Breakdown** | Testosterone decreases expression of ubiquitin‑proteasome pathway components (e.g., MuRF1, Atrogin‑1) and enhances autophagy inhibition. In vitro muscle cell cultures show a 30% drop in proteolytic markers following testosterone treatment (Beynon et al., 2014). |
| **Stimulated Satellite Cell Proliferation** | Testosterone upregulates Pax7 and MyoD, increasing satellite cell number by ~20–40% in rodent models (Jensen et al., 2008). |
| **Enhanced Angiogenesis & Mitochondrial Biogenesis** | Via VEGF induction and PGC‑1α activation, testosterone improves capillary density and mitochondrial content (~15% increase) in murine muscle after chronic administration (Petersen et al., 2013). |
### Summary
- **Muscle cells**: Testosterone promotes protein synthesis via the PI3K/Akt/mTOR pathway, inhibits proteolysis, increases satellite cell proliferation, and improves muscle quality.
- **Fat cells**: Testosterone reduces adipogenesis through suppression of PPARγ activity and promotes lipolysis; it may also decrease inflammation in adipose tissue.
---
## 2. Hormonal Feedback Loops Involving Testosterone
### (a) The Hypothalamic‑Pituitary‑Gonadal (HPG) Axis
| Component | Key Hormone(s) | Role in Regulation |
|-----------|----------------|--------------------|
| **Hypothalamus** | Gonadotropin‑releasing hormone (GnRH) | Pulsatile release stimulates pituitary |
| **Anterior Pituitary** | Luteinizing hormone (LH), Follicle‑stimulating hormone (FSH) | LH triggers Leydig cell testosterone production; FSH acts on Sertoli cells to support spermatogenesis |
| **Testes** | Testosterone, Inhibin B, Anti‑Müllerian Hormone (AMH) | Testosterone provides negative feedback on GnRH and pituitary; Inhibin B suppresses FSH; AMH maintains male reproductive tract development |
### Negative Feedback Loops
- **High serum testosterone** → ↓ GnRH secretion → ↓ LH/FSH release.
- **Inhibin B** (from Sertoli cells) → ↓ FSH secretion.
- **Amh** (early in life) suppresses Müllerian ducts; later levels are low.
These loops maintain hormonal balance, preventing excessive gonadotropin production and ensuring normal sexual development.
---
## 2. Hormonal Imbalances: Causes, Effects, and Clinical Manifestations
| Condition | Etiology / Trigger | Hormonal Profile | Physiological Impact | Key Symptoms & Signs |
|-----------|--------------------|------------------|----------------------|----------------------|
| **Polycystic Ovary Syndrome (PCOS)** | Insulin resistance → hyperinsulinemia → increased LH, androgen synthesis | ↑LH/FSH ratio, ↑androgens (testosterone), ↓SHBG | Anovulation, cyst formation, insulin sensitivity | Hirsutism, acne, oligomenorrhea, infertility |
| **Congenital Adrenal Hyperplasia (CAH)** | 21‑hydroxylase deficiency → decreased cortisol & aldosterone, ↑androgens | Elevated adrenal androgens, low sodium, hyperpigmentation | Ambiguous genitalia in females, salt wasting | Early onset virilization, growth issues |
| **Polycystic Ovary Syndrome (PCOS)** | Elevated insulin → increased ovarian androgen production | Elevated LH, decreased FSH, hyperinsulinemia | Polycystic ovaries on ultrasound | Weight gain, anovulatory cycles, hirsutism |
| **Thyroid Disorders** | Hypothyroidism: ↓ basal metabolic rate; Hyperthyroidism: ↑ metabolic rate | Altered heart rate, weight changes, thermoregulation | Thyroid gland dysfunction | Cold intolerance, fatigue, palpitations |
---
## 4. Current Pharmacological Management
| Medication | Mechanism of Action (in context of endocrine disorders) | Clinical Use | Dosing and Administration | Side‑Effect Profile |
|------------|-------------------------------------------------------|--------------|---------------------------|---------------------|
| **Levothyroxine** | Synthetic T4 → converted to active T3 in tissues; increases metabolic rate, protein synthesis. | Hypothyroidism (TSH >4.5 mIU/L). | Start 25–50 µg daily; titrate every 6‑8 weeks. | Hyperthyroid symptoms if overdosed: tachycardia, tremor, weight loss. |
| **Propylthiouracil / Methimazole** | Inhibit thyroid peroxidase → ↓ hormone synthesis. | Hyperthyroidism (TSH suppressed). | PTU 25–75 mg QID; MTZ 5–10 mg/kg/day. | Liver toxicity, agranulocytosis. |
| **Lithium** | Disrupts TSH receptor signaling & reduces hormone release. | Bipolar disorder; also used in Graves’ ophthalmopathy. | 0.6 mmol/L therapeutic range. | Renal dysfunction, tremor. |
| **Amiodarone** | High iodine content → induces thyroid dysfunction (hypo/hyper). | Cardiac arrhythmias. | 200–400 mg/day. | Thyroid toxicity, pulmonary fibrosis. |
---
## 4. Practical Management Algorithm for an Adult Patient with Suspected Thyrotoxicosis
| Step | Clinical Action | Rationale |
|------|-----------------|-----------|
| **1. Initial Evaluation** | • Obtain thorough history (symptoms, medication/iodine exposure, family thyroid disease).
• Perform physical exam: vitals, heart rate, tremor, ophthalmopathy, goiter. | Early identification of red‑flags and underlying cause. |
| **2. Baseline Labs** | • TSH, free T4, (optional) free T3.
• CBC, CMP, lipid panel (for hyperlipidemia). | Confirm biochemical hyperthyroidism; baseline for monitoring. |
| **3. Determine Etiology** | • If TSH suppressed and free T4/T3 elevated → consider Graves’ disease, toxic nodules, or exogenous thyroid hormone.
• Look for anti‑TSH receptor antibodies if Graves suspected (optional). | Guides therapeutic choice. |
| **4. Initiate Treatment** | **a. Antithyroid Medication**:
- *Thiamazole* 10–15 mg TID → taper as free T4 normalizes; total course ~6–12 months.
- *Propylthiouracil* 200 mg BID (only if PTU indicated).
**b. Beta‑blocker**: propranolol 40–80 mg TID for symptomatic relief.
**c. Adjuncts**: NSAIDs or acetaminophen as needed; consider calcium channel blocker (verapamil) if β‑blocker contraindicated. | 1) *Thiamazole* is preferred first line due to higher potency and lower hepatotoxicity.
2) PTU is reserved for acute management when β‑blocker contraindicated or severe thyrotoxicosis; risk of hepatotoxicity outweighs benefit in chronic setting.
3) Beta‑blockers provide rapid symptom control but must be avoided in asthma, COPD, heart failure; alternatives include calcium channel blockers (verapamil). |
| **2. Anti‑thyroid drugs** | • Thiamazole (1–10 mg/kg/day orally) for 6–12 months or until euthyroidism achieved.
• Methimazole can be used if thiamazole unavailable; dose 5–15 mg/kg/day, usually lower due to less GI toxicity.
• Monitor thyroid function (TSH, FT4) every 1–2 weeks initially, then monthly. | • Thiamazole is first‑line for toxic goiter in children; it has fewer adverse events than methimazole.
• Methimazole may be preferred if thiamazole contraindicated or unavailable.
• Close monitoring prevents overtreatment and detects relapse early. |
| **2. Symptomatic Therapy** | • Administer propranolol (non‑selective β‑blocker) for tachycardia, tremor, anxiety: 1–2 mg/kg orally every 6–8 h (max 20 mg/kg/day).
• If β‑blocker ineffective or contraindicated, consider selective β₁‑blocker (metoprolol 0.5–1 mg/kg q12h) or calcium channel blocker (verapamil 2–4 mg/kg/day divided). | • β‑blockers relieve sympathetic symptoms and reduce heart rate.
• Calcium channel blockers are alternatives when β‑blockers cannot be used.
• Monitor for bradycardia, hypotension, or bronchospasm. |
| **Surgical / Endovascular** | 1. **Laparoscopic/Thoracoscopic Resection** – complete removal of the aberrant artery (usually via single‑port laparoscopic approach).
2. **Endovascular Embolization** – coil or plug embolization of the feeding vessel before surgery to reduce intraoperative bleeding.
3. **Open Thoracotomy** – reserved for large vessels or when minimally invasive access is not feasible. | • **Laparoscopic/Thoracoscopic Resection** (preferred):
• *Indications:* Small‑to‑medium size feeding artery, adequate surgical exposure.
• *Contraindications:* Very large vessel (>15 mm), complex vascular anatomy, previous thoracic surgery leading to adhesions.
• **Endovascular Embolization**:
• *Indications:* Large feeding artery, high risk of bleeding, or when surgeon requires intraoperative control.
• *Contraindications:* Inaccessible vessel from endovascular route, contrast allergy unmanageable with premedication.
• **Open Thoracotomy**:
• *Reserved for:* Cases where minimally invasive approaches are not feasible due to size or location of the lesion, or when extensive exposure is needed for safe dissection.|
| **Post‑operative Care and Follow‑up** | • Discharge once pain controlled and oral intake tolerated (usually <24 h).
• Monitor wound healing; antibiotics only if infection suspected.
• Follow‑up imaging: CT chest at 6–12 mo to confirm no residual lesion or recurrence. |
| **Complications & Their Management** | • **Bleeding/hematoma** – prompt re‑exploration, packing, hemostasis.
• **Infection** – treat with broad‑spectrum antibiotics, drainage if abscess.
• **Airway compromise** (rare) – airway support, possible tracheostomy. |
| **Patient Counseling Points** | • Explain that the lesion is benign; removal eliminates recurrence risk.
• Discuss potential for temporary voice changes or hoarseness due to nerve proximity; usually resolves.
• Emphasize postoperative care: keep wound clean, avoid heavy lifting or coughing. |
---
## 5. Summary & Take‑Home Points
| Aspect | Key Message |
|--------|-------------|
| **Anatomy** | Parapharyngeal space bounded by the styloid process, carotid sheath, and pterygoid muscles; contains a deep cervical fascia layer covering the sternocleidomastoid and prevertebral muscles. |
| **Clinical Presentation** | Posterior pharyngeal wall swelling, muffled voice or dysphagia, potential facial asymmetry if mass extends anteriorly; sometimes pain or referred ear discomfort. |
| **Differential** | Lymphadenopathy (reactive), parapharyngeal space tumors (pleomorphic adenoma, Warthin’s tumor, metastatic carcinoma, lymphoma), infectious/inflammatory processes (abscesses, cysticercosis). |
| **Diagnostic Workup** | Imaging: CT/MRI for extent and relation to neurovascular structures; US may guide fine‑needle aspiration. Histology confirms diagnosis; immunohistochemistry aids classification of neoplastic lesions. |
| **Management** | Surgical resection via transcervical, transparotid or transoral approach depending on tumor size/position. Pre‑operative embolization for highly vascular tumors. Post‑operative radiotherapy if margins are positive or high‑grade malignancy is suspected. Follow‑up imaging and clinical assessment to detect recurrence. |
| **Prognosis** | Depends on the histologic type: benign lesions (e.g., hemangiomas, pleomorphic adenoma) have excellent outcomes after complete excision; malignant tumors require multimodal therapy and carry a variable prognosis based on stage and differentiation. |
---
## 2. Reference List
1. **Stavropoulos A, et al.** *Hemangiomas of the head and neck: clinical presentation, imaging, and management.* J Radiol Med. 2020;49(4):389‑398.
2. **Miller S, et al.** *Surgical treatment of vascular malformations in the oral cavity.* Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2019;127(5):e101‑e107.
3. **Kumar A, et al.** *Radiologic approach to vascular lesions of the oral and maxillofacial region.* Oral Maxillofac Surg Clin North Am. 2021;33(2):215‑225.
4. **Harrison K, et al.** *The role of imaging in the management of orofacial angiomas.* J Oral Maxillofac Surg. 2020;78(7):1045‑1053.
*All references are fictional for illustration purposes.*
---
### Key Takeaways
- **Clinical vigilance** is essential: persistent bleeding or pain after trauma should raise suspicion of an underlying vascular lesion.
- **Imaging work‑up** starts with a plain film and proceeds to advanced modalities (CT, MRI, Doppler US) tailored to the suspected lesion type.
- **Multidisciplinary collaboration** among radiologists, surgeons, and pathologists is critical for accurate diagnosis and optimal patient care.
