Reproductive System 3 PDF

Page 4 Treatment options for Prostate Cancer: o Brachytherapy involves placing radioactive material internally o LHRH agonists lower testosterone production also can be called medical castration because they lower androgen levels just as well as orchiectomy o Orchiectomy is surgery where one or more...

Page 4 Treatment options for Prostate Cancer: o Brachytherapy involves placing radioactive material internally o LHRH agonists lower testosterone production also can be called medical castration because they lower androgen levels just as well as orchiectomy o Orchiectomy is surgery where one or more testicles are removed to reduce androgen levels. This leads to decrease plasma testosterone levels o Abiraterone inhibits androgen production from multiple sources Page 5 Androgen Deprivation Therapy (ADT) principles: o Prostate cells depend on androgens for growth o Dihydrotestoterone (DHT) is a metabolite of testosterone and is a more potent androgen o Testosterone and DHT promote prostate growth o ADT can induce cell death or prevent further growth o Surgical or medical castration and anti-androgen therapy are methods of ADT o Androgen deprivation can help to induce apoptosis (cell death) or at the very least prevent further growth. It can be achieved in two main ways: o Surgical or medical castration stops the production of testosterone o Anti-hydrogen therapy; inhibits the action of testosterone preventing its interaction with the receptors on the prostate cancer cells. Page 7 Side effects of Androgen Deprivation Therapy (ADT): o Loss of libido, erectile dysfunction, hot flashes o Bone density loss, fractures, muscle mass reduction o Changes in blood lipids, insulin resistance, weight gain o Mood swings, fatigue, gynecomastia (breast tissue growth) Page 9: Continuous treatment with GnRH agonists causes a downregulation of GnRH receptors and an uncoupling of the GnRH signal transduction mechanism. This results in a desensitization of gonadotrophs and a marked reduction in the secretion of bioactive LH and FSH. This state is reversible and is called “selective medical hypophysectomy Decrease in circulating LH and FSH, together with downregulation of gonadal receptors for LH and FSH, produces a complete inhibition of testicular or ovarian function and a fall in sex-steroid levels. This state is called “chemical or medical castration.” The key advantage of the medical castration achieved by GnRH agonists is its reversibility. Page 10 DiEthylStilbestrol (DES) in prostate cancer treatment: o Decreases testosterone, DHEA-s, estrone, sex hormone binding globulin levels (SHBG) androgen production o Sex hormone-binding globulin (SHBG) is a protein that binds certain hormones like testosterone. When SHBG level is high, less of these hormones are available o DES exerts these effects through negative feedback on the hypothalamic -pituitary axis resulting in decreased LH secretion and consequent decreased androgen production. In vitro studies also suggest that DES directly suppresses Leydig cell function and inhibits androgen steroidogenesis, further decreasing serum testosterone. o Acts as an anti-androgen in mutated androgen receptor cells o Increases SHBG levels, reducing hormone availability Page 11 Chemotherapy for Hormone Refractory Prostate Cancer: High dose ketoconazole and Taxol/taxotere used Taxol and Taxotere inhibit microtubules to prevent cell division Taxol & taxotere are used for non-androgen dependent prostate cancers Side effects include peripheral neuropathy and hypersensitivity reactions Taxol and Taxotere are microtubules inhibitors. By inhibiting microtubules, they prevent spindle fiber function and thus prevent cancer cells from dividing. Hormone Refractory Prostate cancer occurs when the cancer is recurrent (comes back despite hormonal intervention) Page 14 Erectile Dysfunction (Impotence): Consistent inability of adult male to hold an erection long enough for sexual intercourse Causes include psychological, physical factors like diabetes, vascular issues, neurological disturbances, testosterone deficiency, drugs (alcohol, nicotine, antidepressants, tranquilizers, etc) Sildenafil (Viagra) causes vasodilation for erection Page 15 Mechanism of action of Sildenafil (Viagra) for Erectile Dysfunction: o Vasodilation of penile arteries through nitric oxide (NO) pathway o Increased cGMP levels lead to smooth muscle relaxation and increased blood flow o Sildenafil enhances the effects of NO for maintaining an erection Page 16 Phosphodiesterases are enzymes that break down phosphodiester bonds in nucleotides o Different subtypes of phosphodiesterases have varying affinities for different substrates like cGMP and cAMP Properties of human phosphodiesterases (PDEs) are listed in a table o Different PDE subtypes have different localizations and affinities for substrates like cGMP and cAMP Page 18: What is STD? An infection that can be transmitted through sexual contact with an infected individual. They are sometimes called sexually transmitted infections (STIs) STDs can be transmitted many different ways, but most can be passed by: Vaginal sex, Anal sex, Oral sex, Skin-to-skin contact, Infected Mother to child. Page 19 Sexually Transmitted Diseases (STDs) can be transmitted through various forms of sexual contact More than 2.4 million cases of syphilis, gonorrhea, and chlamydia were reported in the US in 2018 o Many infections show no signs or symptoms, leading to untreated cases and potential long-term damage CDC reported a rise in STD cases in the US, including congenital syphilis linked to newborn deaths Often no signs or symptoms - People are unaware of infection - and don’t receive treatment - Long-term damage - May have passed infection to others. Page 21 Chlamydia is a common sexually transmitted disease caused by Chlamydia trachomatis bacteria. Spread through sexual contact vaginal, anal, or oral sex with someone who has chlamydia or from infected pregnant women to their babies during childbirth Page 22 Symptoms of chlamydia include abnormal discharge, burning sensation when urinating, rectal pain, and swelling in testicles Complications of chlamydia can lead to Sterility or infertility Infection spreading to vas deferens (causing pain and/or fever) Pelvic Inflammatory Disease (PID) -Long-term abdominal/pelvic pain -Scar tissue formation in fallopian tubes -Ectopic pregnancy Chlamydia is often referred to as the "Silent" Disease due to its asymptomatic nature Page 25 Gonorrhea is the second most common STD in the US, with an estimated 616,392 new cases in 2019 Spread through sexual contact; vaginal, anal or oral sex or from infected pregnant women to their babies during childbirth Page 26 Symptoms of gonorrhea include painful or burning sensation when urinating, abnormal vaginal/penile discharge (white, yellow, or green) and reectal discharge, itching, soreness, bleeding Vaginal bleeding between periods Painful or swollen testicles (less common Complications of gonorrhea can lead to sterility or infertility, disseminated infection (rash, arthritis, fever, meningitis, etc) and Painful infection of tubes attached to the testicles. Pelvic Inflammatory Disease (PID) -Scar tissue formation in fallopian tubes Ectopic pregnancy -Inability to get pregnant -Long-term pelvic/abdominal pain Men with gonorrhea tend to have more obvious symptoms compared to women who are often asymptomatic Page 29 Pelvic Inflammatory Disease (PID) is a serious infection affecting a woman's reproductive organs, often caused by untreated STDs (like chlamydia and gonorrhea). May experience mild or no symptoms. Symptoms of PID include lower abdominal pain, fever, unusual discharge with bad odor from your vagina, pain and or bleeding during sex. Burning sensation when you urinate Bleeding between period. Complications of PID include scar tissue formation outside and inside the fallopian tubes(blockage), ectopic pregnancy, infertility, and long-term pelvic pain Page 30 Primary & Secondary Syphilis are stages of syphilis caused by the Treponema pallidum bacterium Syphilis can be spread through direct contact with a syphilis sore (chancre) during vaginal, anal or oral sex. And from mother to baby Primary syphilis presents with painless chancres that appear on the body after exposure to the infection Primary Syphilis then goes to Secondary Syphilis then to Tertiary/Late Syphilis Page 31: Primary Syphilis Chancre - syphilis sore Firm, round, and painless Appears within 2-6 weeks after exposure (could take up to 3 months) Found on the part of the body exposed to the infection (penis, vagina, anus, lips, in rectum, or in mouth) Typically disappear after a few weeks without treatment (still progresses to next stage) Page 32: Secondary Syphilis Appears about 4 weeks after chancre heals. Will go away without treatment, but infection will progress. Symptoms include: o Condylomata lata or “fleshy warts” in anogenital region o Alopecia or patchy hair loss non-itchy o non itchy rash with rough red or reddish brown spots o Mucous Patches usually in the mouth, vagina, or anus Page 33: Primary and Secondary Syphilis Rates Reported rates by age and sex in the U.S. in 2017 Men had higher rates compared to women across different age groups CDC data shows varying rates per 100,000 population based on age and gender Page 34: Late (Tertiary) Syphilis Typically occurs 10-30 years after infection begins Can damage various body parts like heart, brain, spinal cord, eyes and bones leading to severe consequences like mental illness, deafness, disease, blindness, and death Types include Cardiovascular Syphilis, Late Benign Syphilis, and Neurosyphilis Gumma: a soft, gummy tumor, is a characteristic feature Page 35: Genital Herpes (HSV-2) Spread through vaginal, oral, or anal sex, and skin-to-skin contact with someone who has the virus Symptoms include blisters around the genitals, rectum, or mouth, leading to painful sores that weeks to heal. These symptoms are sometimes called “having an outbreak” No cure available, with outbreaks being common 1 in 8 people aged 14-49 have genital herpes, often without knowing it Genital herpes is an STD caused by two types of viruses. The viruses are called herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2) Page 36: Human Papillomavirus (HPV) Transmitted through skin-to-skin contact and vaginal, anal, oral sex (vaginal & anal most common) HPV is highly common, with an estimated 80% of sexually-active individuals getting at least one type of HPV HPV is a major cause of cervical cancer, affecting a significant percentage of sexually active women. Cervical cancer being the second most common cancer after lung cancer, affecting women of different age groups; has a prevalence of about 20% in young sexually active women HPV16 is a prevalent strain causing cervical cancer and is sexually transmitted Page 37: HPV-Related Health Problems Include genital warts, cervical pre-cancer, and various HPV-related cancers HPV is often asymptomatic, leading to many individuals being unaware of their infection While there is no direct treatment for the virus, but there are treatment for health problems it cause In most cases, the immune system will overcome HPV on its own #1 cause of cervical, anal, and penile cancers