Reproductive system 2.pdf

Page 3 Gamete Development and Disorders of the Male Reproductive System o Spermatogenesis o Androgens o Clinical Issues with the Male Reproductive System § Androgen Deficiency § Prostatitis § Benign Prostatic Hypertrophy § Prostate Cancer Page 5 The cell in the testes that makes testosterone is call...

Page 3 Gamete Development and Disorders of the Male Reproductive System o Spermatogenesis o Androgens o Clinical Issues with the Male Reproductive System § Androgen Deficiency § Prostatitis § Benign Prostatic Hypertrophy § Prostate Cancer Page 5 The cell in the testes that makes testosterone is called Leydig cells. Page 6 Hormonal Regulation of Spermatogenesis o FSH Receptor: GPCR adenylyl cyclase activation leads to cAMP production, protein kinase A activation, and protein phosphorylation. o FSH binding increases intracellular calcium, activates mitogen-activated protein kinase, and stimulates inositol triphosphate. Page 7 Testosterone Synthesis in Leydig Cells o StAR (Steroidogenic Acute Regulatory Protein) moves cholesterol from the outer to inner mitochondrial membrane. o ScarB1: Gene encoding the plasma membrane receptor (SRB1) for high density lipoprotein cholesterol (HDL). Mediates cholesterol transfer to and from HDL o Four steroidogenic enzymes catalyze the biosynthesis of testosterone: CYP11A1, 3β HSD, CYP17A1, and 17β-HSD3 are involved. Page 8 Key Hormones and Pathways o GnRH from the hypothalamus stimulates FSH and LH release. o Leydig cells produce testosterone. o Androgen Binding Protein (ABP): Secreted by Sertoli cells and keeps testosterone concentrations at an elevated level within the tubule Page 9 Sperm Production o Maturation takes 74 days. o Sperm spend 50 days in testicles and 22-24 days in the epididymis. o Sperm mature in the epididymis and gain motility. o During sexual activity, motile sperm are ejaculated into the female reproductive tract o Each ejaculate contains millions of sperms: 5,000,000-300,000,000 sperms Page 11 Androgens o A type of hormone that promotes the development and maintenance of male sex characteristics. Natural Androgens: From testes: Testosterone (5-12 mg/day) Dihydrotestosterone (more active) Synthesized by 5 a-reductase. o Weak androgen from the adrenal cortex: Dehydroepiandrosterone (DHEA); Androstenedione o A number of studies have found that DHEA supplements may help people with depression, obesity, lupus, and adrenal insufficiency. DHEA may also improve skin in older people and help treat osteoporosis, vaginal atrophy, erectile dysfunction, and some psychological conditions. But study results are mixed and often contradictory o Female testosterone: 0.25-0.5 mg/day (ovary + adrenals) Page 15 Androgen Deficiency o Occurs when testosterone levels fall below age-related norms. o This condition is also commonly known as male hypogonadism if the cause is deficiency in testicular production of reproductive hormones. o Can be treated with testosterone replacement therapies. o Low androgen levels can lead to sexual development issues and infertility in younger people Page 16: How is androgen deficiency treated? Testosterone replacement therapies are a common method of treatment for patients with androgen deficiency. Testosterone replacement therapies exist in a variety of preparations. These include long and short acting intramuscular injections (injections made into the muscle tissue), transdermal (skin) and scrotal patches, transdermal gels and oral preparations. The appropriate therapy will be determined in consultation with the patient and specialist. Page 18: Prostate Clinical Issues (Prostatitis) o Epidemiology of Prostatitis § Prevalence ranges from 2.2 to 9.7%. § History of STDs increases risk. § Prostatitis symptoms linked to BPH(benign prostatic hyperplasia), lower urinary tract symptoms and prostate cancer. § Patients with previous episodes and more severe symptoms are at higher risk for chronic pelvic pain Page 19 Prostatitis o Inflammation of the prostate gland with different types. o Type I (acute bacterial) o Type II (chronic bacterial) o Type III (chronic prostatitis/chronic pelvic pain syndrome) o Type IV (asymptomatic inflammatory chronic prostatitis) o Occurs in men 50 years or younger o Narrowed urethra can cause painful/burning during urination, pain in the groin, cloudy/blood stained urine. o Antibiotics for appropriate duration, fluids to flush out infection. Sitz bath can help alleviate symptoms. Prostatitis Symptoms: Acute: sudden fever & chills Perineal, rectal or low back pain Dysuria, frequency, urgency & nocturia Chronic: perineal discomfort burning, urgency & frequency pain with ejaculation prostatodynia (pain in prostate with voiding) Perineum: the area between the anus and the scrotum or vulva. Complications: o Enlarged prostate o Urinary retention o Epididymitis: inflammation (swelling and irritation) of the epididymis o Bacteremia: presence of bacteria in the bloodstream o Pyelonephritis: infection that travels to one or both of the kidneys Treatment: o Hospitalization for IV antibiotics o Analgesics o Antispasmodics & bladder sedatives o Stool softeners o Bedrest o Sitz baths Benign Prostatic Hypertrophy (BPH) Characteristics: o Progressive enlargement with age o Results in Obstructive urinary disorder(lower urinary tract symptoms,LUTs) o Most common neoplastic growth in men >50 o Virtually ALL men greater than 50 show some increase in prostate size. Symptoms: o Early symptoms: hesitancy, decreased force, frequency, nocturia o Bladder muscles hypertrophy can occur and may temporarily reduce symptoms o Late changes: When hypertrophy is no longer effective, muscles decompensate & bladder wall becomes noncompliant & hypotonic o Post void residuals lead to increased infections & hydronephrosis Hydronephrosis is the swelling of a kidney due to a build-up of urine Treatment: o Medication: alpha-adrenergic blockers: terazosin (Hytrin), doxazosin (Cardura), tamsulosin (Flomax), alfuzosin (Uroxatral), and silodosin (Rapaflo) o antiandrogen agents o 5-α-reductase inhibitors to reduce DHT levels: Finasteride, Dutasteride. o Procedures: TUIP, transurethral needle ablation, microwave thermotherapy BPH: Transurethral Incision of the Prostate (TUIP) used to treat slightly enlarged prostate - laser incisions in prostate to decrease resistance to urinary flow (outpatient procedure) Transurethral needle ablation: use of localized heat to destroy prostate tissue which body reabsorbs Microwave thermotherapy: Via transurethral probe. Tissue is sloughed. Prostate Cancer Overview: o Leading male cancer death o Asymptomatic initially o Late symptoms: urinary obstruction, painful ejaculation, hematuria Detection: o PSA test annually in men >50 o DRE and TRUS for screening o Gleason Score for grading Stages: o Stage I to IV based on spread o Metastatic cancer involves other organs Pathophysiology: o Genetic and environmental factors play a role o Molecular changes in prostate cancer development Additional Information PSA: Produced by prostatic tissue Elevated in infection, BPH, or cancer Gleason Score: o Common grading system for prostate cancer o Anaplastic: A term used to describe cancer cells that divide rapidly and have little or no resemblance to normal cells Urinary Retention: o Condition affecting bladder emptying Transrectal Ultrasound: o Assists in guiding prostate biopsies Treatment: o Varies based on the stage and severity of the condition o o Medical Note: Prostate Cancer Detection and Treatment Page 39: Prostate Cancer Detection o Indium In 111 capromab pendetide (ProstaScint) is a radiolabeled monoclonal antibody targeting prostate-specific membrane antigen (PSMA). § Attracted to PSMA found on prostate cells. PSMA studies are conducted on newly diagnosed prostate cancer patients to detect metastasis to pelvic/lymph nodes. o Also performed on post-prostatectomy patients with elevated PSA levels. o Page 40: Prostatectomy o Types: § Radical Prostatectomy: Removal of prostate, seminal vesicles, vas deferens, fat, nerves, and blood vessels. § Suprapubic Prostatectomy: Rare, associated with incontinence, impotence, rectal injury. § Retropubic Prostatectomy: Better blood loss control but higher infection risk. § Laparoscopic/robotic radical prostatectomy: Enhanced visualization, less bleeding/pain, reduced impotence/incontinence risk. o Purpose: Partial or complete removal of the prostate for prostate cancer or benign prostatic hyperplasia. Page 41: Treatment of Prostate Cancer o Brachytherapy: Involves placing radioactive material inside the body, a type of radiation therapy for cancer. § Also known as internal radiation. o LHRH Agonists: Drugs reducing testosterone production by the testicles. § Also called LHRH analogs or GnRH agonists. o Orchiectomy: Surgical removal of one or both testicles, reducing androgen levels (medical ca