Patient description: A 46-year-old man presents with dizziness and frequent headaches. He has a family history of CAD, but no other cardiovascular risk factors such as smoking, high blood pressure, and diabetes mellitus and is physically active. The patient's LDL-C and HDL-C levels were 545 and 53 mg/dL, respectively. His fasting glucose and triglyceride levels (85 and 158 mg/dL, resp.) were within normal limits. The patient reported no use of lipid-lowering medications. Neck auscultation revealed a systolic murmur 3+/6+ in the neck, radiating to the skull. Ultrasonography of the carotid arteries, revealed severe stenosis in the left internal carotid artery (LICA), as well as moderate stenosis in the right internal carotid artery (RICA) estimated between 40% and 50%. For the LICA, the peak-systolic (PSV) and end-diastolic velocity (EDV) cutoff values were 208.5 cm/s and 54.5 cm/s, respectively; RICA PSV was 91.72 cm/s and RICA EDV was 37.37 cm/s. Plaque was observed in the anterior and posterior walls of the internal carotid artery and common carotid artery, which were characterized as bulky plates extending to the middle third of the internal coronary arteries (ICAs) and as predominantly echogenic and hyperechoic, with less than 50% of the area being echolucent with uneven surfaces.

Clinical trial eligibility criteria: eligible ages (years): 18.0-65.0,  Hypogonadism Opioid-Related Disorders Male Infertility Male years to 65 years Low testosterone as defined by (serum total testosterone <350 ng/dl in men <55 years, <300 ng/dl in men 55-65 years) taking opioid pain medication (see A below) OR planning to start new pain medication regimen (see B below) A) continuous opioid treatment for chronic nonmalignant pain for >=6 months receiving one of several specified opioid regimens for the past 1 month (including >=20 mg/day of oral methadone, >=30 mg/day of oral sustained release oxycodone, >=30 mg/day of oral morphine sulfate, >=6 mg/day of oral dilaudid or >= 8 mg/day of dilaudid ER, or >=25 mcg/hr of transdermal fentanyl or buprenorphine, or intrathecal morphine pump) B) OR the pain management physician is planning to start pain medication (opioid or non-opioid pain therapy) but you have not received it yet. If this is the case, your testosterone will be checked before starting and during 1 month of pain therapy to determine if you have low testosterone to qualify to begin medication (clomiphene or placebo) treatment in this study BMI (20-35 kg/m2) Presence of clear secondary hypogonadism with hypogonadal symptoms and low total testosterone level (confirmed with morning testosterone level <= 350 ng/dL for men age >= 55 and <= 300ng/dl for men age 55-65) or total testosterone <=200 ng/dl (regardless of symptoms). Additionally luteinizing hormone (LH) should be <15 mIU (milli-International unit )/mL (at baseline only). Symptoms of hypogonadism fatigue, decreased energy level/endurance, depressed mood, decreased libido, erectile dysfunction Chronic nonmalignant pain etiology includes rheumatoid arthritis, osteoarthritis, spinal stenosis, polymyalgia, complex region pain syndrome I and II, neurinoma, phantom limb pain, neuropathic pain of other origin, scoliosis, neck pain, failed back surgery, or chronic pancreatitis All patients must have ability to complete the study in compliance with the protocol, and the ability to understand and provide written informed consent  Chronic pain of malignant etiology (cancer-related) Preexisting testosterone deficiency Concomitant use of medication that could interfere with testosterone levels including antidepressant medication, spironolactone, cimetidine, clomiphene (use in the past 1 year), human chorionic gonadotropin (hCG), androgen, estrogen, anabolic steroid, 5-alpha-reductase inhibitors such as finasteride, dehydroepiandrosterone (DHEA), testosterone therapy (topical testosterone within 7 days of study, injectable testosterone within 6 months of study) Uncontrolled hypertension Clinically significant abnormal findings on screening examination based on the Investigator's assessment Known hypersensitivity to clomiphene Symptomatic cataracts Presence or history of known hyperprolactinemia with or without a tumor End-stage renal disease Any contraindication to testosterone supplementation therapy