10. male reproductive system + STIs

sperm delivery -> ejaculation

urine excretion (urethra)

increase parasympathetic -> vasodilation -> corpus fill up with blood (spongy like tissues)

- you need to be a certain level of relaxed because it includes PNS (rest + digest)

- some modulation by CNS = some voluntary control, but only modulation not initiation or stopping it

- ejaculation requires SNS

in vitro, happens until you die

tip of it, most sensitive part

- equal to the clitoris, it actually was that and then move outward and became the tip

NO

emission needs to happen for ejaculation

bag of the skin that encompasses the testes

to decrease the temp of testes by 1-2 degrees -> optimal spermatogenesis temp

based on outside temp

- if its really cold/warm, will move based on reflex muscles to adjust its temp to optimal spermatogenesis

1- spermatogenesis

2- sex hormone synthesis

male "ovaries"

seminiferous tubules

- squiggly canals coiled up of one another

- if u look inside the canals, a bunch of cells on the outside slowly developing the sperm swimmers

cells that are responsible for producing testosterone in response to FSH and LH

- sit outside of tubules in testes

testosteorne

androgens

leads to fetal differentiation

- presence of Y chromosome stimulates production of testosterone

- leads to reproductive organ development (male)

increase during fetal development, but then it comes to a plateau until puberty, where leydig cells will wake up again and start producing to complete sexual maturation

bone growth

bone marrow = stimulation of stem cells for RBC production

kidneys - stimulate of EPO production

muscle mass

larynx = deepens voice

skin = hair growth

liver = synthesis of serum proteins

less aromatase = enzyme that converts testosterone to estrogen

mostly on muscle tissue

- binds to androgen receptors

transforming it into dihydrotestosterone (DHT) using enzyme 5alpha-reductase

- amplification pathway

- only about 5-10% of testosterone becomes DHT

- DHT produces most effect = almighty testosterone

98% of it is bound to sex hormone binding globulin (SHBG), a little transporter protein

- alterations to this protein can lead to drastic effects in testosterone cuz hormones that are bound to proteins cannot bind to receptors to exert effect

- so only the 2% free concentration would have effect

- even small changes in SHBG can have huge effects

feedback loop

hypothalamus releases GnRH on pituitary -> releases FSH and LH

- LH stimulates Leydig cells to produce more testosterone

- FSH stimulates Sertoli cells (=granulosa cells in women) to express testosterone receptors

Sertoli cells provide nutrients to developing sperm in response to presence of testosterone

developing spermatids undergo DNA duplication (mitosis + meiosis), basically 1 single cell divides into 4 spermatids

sperm becomes haploid with DNA packed in acrosome (head)

swim in tubule to reach next organ called epididymis, where they will complete their maturation

at puberty until death

70-80 days

1000 sperms per heartbeat

coiled shape tube on top of testes, just before vas deferens

- 6 meters long when uncoiled

1- sperm conduction

2- sperm maturation

average 12 days

they improve:

- motility skills

- fertilization power

glucose gives them energy

testosterone helps them mature

vas deferens (x2) = conduction cords that bring the sperm out towards the penis for ejaculation (vasectomy cuts this)

ejaculatory duct

urethra

sperm transport + ejaculation

glands secrete fluid within the ducts

prostate gland

seminal vesicle (2)

Cowper glands (2)

release alkaline nutrient-rich fluid secretion

increase sperm motility + survivial

sperm (2%) + gland fluid (98%) = semen

even if you have a vasectomy you can still ejaculate, there would jus not be any sperm in it

ejaculation = semen excretion

emissions = strong rhythmic contractions of urethra + penile muscles + vas defers + epididymis

emission ALWAYS precedes ejaculation

75-400 million (1-4mL)

basically = menopause

- steady decline in testosterone levels with age

For the same age:

the reproductive capacities of males are still greater for the same age as a female

quality of sperm > ovule quality

- you are born with all your ovules, but sperms are constantly being made, they are "new

- sperm is never as old as person is

1- erectile dysfunction

- ↑ Stimulation Requirements

- Longer Refractory Periods (time between erection, like where it is impossible)

- ↓ Ejaculate Volume

2- hypogonadism (decline in gonads of testes)

- ↓ Sperm Motility & Fertilization Power

- Testes Atrophy

- Seminiferous Tubule Collapse & Fibrosis

3 - ↓ Testosterone

- ↓ Responsiveness to FSH & LH- ↓ Leydig Cells # & Function- ↓ Muscle Mass; Cognitive Functions & Libido

scarring/fibrosis of urethra - narrowing of urethra, makes it difficult to pass through + painful

Incidence ↑ with age

Risk of Hydronephrosis (kidney injury) & Renal Failure

chronic use of catheters

trauma

genetic

• ↓Urinary Force + Frequency

• Infection: UTIs, abscesses• Bladder obstruction• Difficult/painful ejaculation

foreskin disorder

- phimosis = difficulty retracting foreskin

- paraphimosis = difficulty covering foreskin

Abnormal only if 3+ years old

Circumcision = Good Treatment

Poor Hygiene

Chronic Penile Infections

Diabetes + Age

• Edema & Erythema (redness)

• Purulent Discharge

Phimosis → Paraphimosis

Phimosis → Urinary Obstruction

Paraphimosis → Glands Necrosis

Local Vasculitis (caused by decrease in O2) & Penis Tissue Fibrosis

• Curvature • Incidence of Sexual Dysfunction

unknown cause

• Diabetes (damage due to excessive blood glucose in the bloodstream)

Keloids Development (abnormal scarring)

Beta-Blocker Use (Rare)

Painful Erections

Incomplete Erections

Painful Intercourse

Painful prolonged penile erection

• Not associated with sexual arousal

- could be excessive intake of viagra

EMERGENCY!

- Risk of sexual dysfunction

60% idiopathic

40% known associated causes:

• Spinal cord trauma

• Infections• Sickle cell disease

penile necrosis because the constriction of the base would be depriving top of penis from O2 blood

injection of saline solution

Spermatic Cord Vein Dilation (major vein that brings O2 blood from testes to circulation)

Incidence = 10-15% of Men; 90% on Left Side

Unilateral Right Side = Inferior Vena Cava Obstruction

Incompetent/Absent Valves (blood pools in testes due to gravity which dilates vessel)

Reduced Testis Blood Flow (prevents pressure from pushing it back into circulation)

"bag of worms" feeling

↓ Spermatogenesis/Fertility (cuz of less O2)

Testicular Fluid Accumulation (mostly water based)

• Incidence = 6% of newborns → resolves by 1y.o.

Causes:

• Local Trauma or Infections

• Radiotherapy

- Testicular Cancer → Screen for Cancer!

- Adult Chronic Hydrocele → Scrotal Secretion Imbalance

acute testicular infection

Causes:

Systemic Infection that make their way into testes

Epididymitis Complication

• Mumps

most common for infection from urethra to go up

Manifestations:

Fever

Local Erythema & Edema

Hydrocele

Testicular Atrophy

↓ Spermatogenesis & Infertility

Twist of Scrotal Blood Flow

Acute Scrotum = Pain & Swelling

Most common in Newborn & Pubertal Adolescents

Causes:

• Spontaneous• Physical Exertion

• Trauma

Clinical Manifestations:

↓ Blood Flow causes ischemia of testis

High-Riding Tender Testis

Cannot identify epididymis - inflammation + necrosis

Inflammation of Epididymis

Sexually Active Males

Unprotected Anal Sex ↑ Risk

Causes:

• Infection (Gonorrhea/Bacterial)

• Chemical (Urine Reflux)

Clinical Manifestations:

• Acute & SeverePain

Urethral Discharge

Edema: Epididymis, Scrotum & Spermatic Cord

Complications:

• TestesAbscess & Infarcts

• Infertility

Enlargement of Prostate Gland (increase in # of healthy cells)

Local Inflammation & Angiogenesis

Begins ≈ 40-45 until death

Causes:

• Endocrine & GF Imbalance

• Aging & Testosterone

• Estrogen

Clinical Manifestations:

• Urethra Compression → Flow Obstruction

Long-Term:• Incomplete Bladder Emptying

• ↑ Bladder & Kidney Infections

Male Breast Tissue Hyperplasia

40% of males

Mostly Adolescents and 50+

Causes:

• Estrogen-Testosterone Imbalance 1. ↑↑ Estrogen / Normal Testosterone (more teens)

2. Normal Estrogen / ↓↓ Testosterone (more old)

• Change in breast tissue response to hormone

surgery can be done

Any Impairment in: Libido, Erection, Emission or Ejaculation

- Can lead to Psychological Complications (Anxiety, Depression)

classic viscous cycle of erectile dysfunction

prevalence of premature ejaculation and low libido is the highest

- harder to target

vascular

chronic disease

surgical/pharmacological

penile trauma/disorder

neurologic

lifestyle

endocrine

psychological

lifestyle

neurologic

see how there is a cross over

↓ sperm production

- chemotherapy

- HTP axis dysfunction

- testicular tauma

- leydig/sertoli cell dysfunction

- chronic disorders

- genetic disorders

↓ sperm quality

- genital infection

- radiation/oxidative stress

average = 50-100 million/ml

min = 20 million/ml

male hypogonadism

- Pre-pubertal inadequate testosterone production

- Long-acting parenteral preparation

- Induces Puberty

replacement therapy

- Adult-onset inadequate testosterone production

- Restores libido & secondary sex characteristics

- Does not improve fertility

delayed puberty

- Usually hereditary late puberty- Only treat if external pressures affect patient’s health

replacement therapy for menopause (off label use)

- Lower dosage than for male replacement (avoid developing male characteristics)

- indirect way of giving estrogen (remember aromatase)

- Alleviates some menopausal symptoms

- Fatigue, ↓ libido, genital sensitivity

others

- Female-to-Male Transitioning

- Cancer or AIDS-induced Cachexia (body wasting)

- Anemias: boost secretion of EPO

Development of Male Features

- Pregnancy = Contraindication

- Exception: Sex Transition

Premature Epiphyseal Closure

- Pediatric concern

- Decreases adult height

Hepatotoxicity

- Common with Long-term use

- Frequent LFT (test)

Do not cause cancer mutations but promote existing prostate tumors

Dyslipidemia → Atherosclerosis risk

- increases LDL and decreases HDL

Evidence: Muscle Mass Increase after 10 weeks

long term harm >>>> short term benefits

Serious toxicity

Liver cancer

Hypertension & CVD

Infertility

Abstinence & Withdrawal Syndrome like opioids, cocaine...

renal/cardio drugs:

- beta blockers

- thiazide diuretics

- aldosterone antagonists

CNS drugs:

- antipsychotics

- mood stabilizers

- MAOIs

- SSRIs : fluoxetine is the biggest one

- alcohol

urogenital drugs:

- 5-alpha-reductase inhibitors

and many more

Risk factors for ED are similar for CVD:Aging, Smoking, Diabetes, Obesity, Dyslipidemia, etc.

Many males reported experiencing ED in the months prior to a 1st Heart attack!

so maybe

sexual arousal -> ↑ PNS signals to penis -> ↑ release of nitric oxide -> produces more cGMP

- produce relaxation of arterial smooth muscle in penile area to allow for more blood flow for erection

PDE5 inhibitors

- enzyme that breaks down cGMP into GMP

- cGMP remains in action longer where blood can rush into penile tissue

sildenafil (viagra)

- half life = 4 hr

- duration of action = 4hr

- metabolism = CYP3A4

tadalafil (cialis)

- half life = 17.5 hr

- duration of action = 36hr

- metabolism = CYP3A4

Boosts normal erectile response to stimuli

- Does not cause erections

Benefits in Males with ED

70% vs. 20% for placebo, regardless of ED cause

Little to no effect in males without ED

Safe but inefficient for female libido

Priapism

• Painful erection > 6 hours• Irreversible damage if > 24hours• Treat with blood aspiration or saline irrigation

Rare & Unclear ADRs

• Optic neuropathy causing vision loss• Ear damage, causing sudden hearing loss

Nitrates

• Contraindicated• Wait 24 hrs before giving nitrate

cause severe hypotension

Alpha Blockers

• Use with caution

cause severe hypotension

CYP3A4 Inhibitors

• ↓ Sildenafil dosage

Class I & III antidysrhythmic drugs

• No interaction for Sildenfil but risks with other ED Rx

Sildenafil is safe for men with CHD

• Heart attacks during sex caused by sexual activity, NOT Sildenafil

• Educate patients about risk of moderate physical activity

Severe Sx → Invasive therapy

Moderate Sx → Drug therapy

Mild Sx → Watchful Waiting

5-alpha reductase inhibitors

- finasteride

alpha1-adrenergic antagonists

Inhibits 5α reductase Type II↓ testosterone conversion to DHT↑ serum testosterone, ↓ prostatic volume

Benefits: ↓ static urethral obstruction (blocking urethra)

• Most effective in large prostate• Delayed effect of several months (gradual decrease)

Expect 30-50% ↓ in PSA levels• If not, evaluate for prostate cancer (just a warning sign to evaluate)

CNS

• Sexual dysfunction / infertility

• Depression

Cardiovascular

• Orthostatic hypertension

• Angioedema

Cancers

• Prostate cancer

• Breast cancer

Pregnancy -> used against hair loss, not BHP

• Teratogenic for male fetus

Benefits: ↓ dynamic urethral obstruction (spasms)

Relaxes smooth muscles

Does NOT ↓ prostate size or PSA levels

Preferred over 5-α-Reductase Inhibitors for mild BPH

Silosidin

Inhibits α1-A receptors (specific for prostate)

No effect on BP

Adverse Effects

• ↓ Ejaculate volume

Terazosin

• Not specific for prostate

• ↓BP

Adverse Effects

• Hypotension & dizziness• Caution if combined with other hypertensive Rx

but both well tolerated and efficient

Sexually Transmitted Disease

- Disease: Symptoms are present

Sexually Transmitted Infection

- Infection: Symptoms may or may not be present, but transmissible

Sexually Transmissible and Blood-Borne Infections

- Includes infections that are sexually transmitted and/or transmitted through blood

• < 25 & Female = ↑ Risk : bigger area of entry, and shorter urethra, cervix immature

Unprotected Sex

Drug Use

Consequences: ↑ Risk of:

• Mortality

• Infertility

- Birth Defects

- Genital Cancers

young people aged 15-24

gay + bisexual

pregnant women

Bacterial• Caused by a bacterial infection

• Active infection can be cured (but cure doesn’t mean damage is reversed)

• Self-limiting (exception: syphilis -> will become BAD if not treated)

examples:

• Gonorrhea

• Syphilis• Chlamydia* - behaves like virus though

Parasitic

• Caused by an organism living & feeding off the human body

examples

- scabies (mites)

• Caused by a virus• Harder to cure, though symptoms may subside

• Higher rates of negative outcomes if untreated

examples:

• Genital Herpes (HSV1, HSV2)

• Human Papillomavirus (HPV)

• Hepatitis B (HBV)

• Human Immunodeficiency Virus (HIV) and Acquired Immunodeficiency Syndrome (AIDS)

Parasitic Infection → 1st Human Disease with Known Cause

Transmission: Long Skin Exposure to Parasite (Ex.: Intercourse or Fomites)

Severe Pruritus = Itching at Infection Sites

Persist post-treatment

Hypersensitivity Reactions → Spreading Scratching → Secondary Infections

Transmission: Blood (Needles, Intercourse, Congenital)

Liver Infection → Jaundice, Fatigue, Nausea, Urticaria

Subset develop Chronic Disease → Chronic Hepatitis; Cirrhosis; Cancer

C.Trachomatis → Obligate Bacterial Infection → Behaves like a Virus

Leading Cause of Preventable Infertility & Ectopic Pregnancies

- Incidence: Most common STI

- Prevalence ↑ due to ↑ Screening & Self-Report & Asymptomatic cases

Transmission: Intercourse & Congenital

female manifestations:

- none

- unusual discharge

- abnormal bleeding

- pelvic pain

- pain during sex

male manifestations:

- sore testicles

- unusual discharge

- feeling ill

- anal discharge

- sore throat

bacteria can reproduce on their own outside of host cells

- virus needs to enter our cells to reproduce

- chlamydia needs to enter to reproduce

neisseria gonorrhoea bacteria (gram negatie + aerobic)

- affects genitals, but can affect rectum + pharynx

- only infects humans

male Sx:

- White/green/yellow urethral discharge 1-14 days after

male complications:

- infertility

female Sx:

o   Painful urination

o   Increased discharge

o   Bleeding

female complications

§  Spread to infect the fallopian tubes or uterus

§  Causes pelvic inflammatory disease

if untreated can spread to blood:

disseminated gonococcal infection (DGI)

§  Can be life threatening

§  Cause arthritis

§  Other forms of inflammation

§  Use pili to help them cause damage

·       Attach to host cell

·       Transfer genes

·       Provide motility

§  Express outer membrane proteins to help evade the immune system

§  When it enters the body, it attaches to mucosal cells using their pili

·       The epithelial cells are lining the body cavity within the reproductive tract

§  Then pass through the cells into the subepithelial space to establish infection

·       Layer just beneath surface

§  Lipooligosaccharide in the cell wall stimulates an inflammatory response

·       This is what causes most symptoms

§  Can replicate within immune cells like phagocytes

o   Culturing swab specimen in lab

o   Testing swab specimens using nucleic acid amplification testing

o   Before antibiotics: Mercury, Arsenic, Bismuth, Dried powered fruits

o   Antibiotics

§  Now ceftriaxone + azithromycin

§  Some strains have become resistant to everything except cephalosporins

·       Seems like untreatable gonorrhea will happen soon

condoms

o   Infection caused by bacteria called Treponema Pallidum

o   Most commonly spread by

§  Oral sex – biggest one

§  Vaginal sex

§  Anal sex

primary syphilis

§  Mostly painless

§  Ulcer or chancre anywhere on body

·       Most commonly on lips/tongue, vagina, anal area

§  Patient often don’t realize they have one because it is painless

secondary syphilis

§  Where it usually gets discovered, 2-6 months post

§  has spread all around body

·       Rash on palms, feet, chest

·       Headaches, dizzy, hearing problems

·       Swollen lymph glands

tertiary syphilis

§  Dormant for 10-30 years -> dangerous

§  Can affect brain

·       Dementia Alzheimer’s/dementia

§  Can affect heart

·       Aneurysms

§  Can affect bone health

blood test or swab of ulcer

Has not become resistant to antibiotics

§  Fully sensitive to penicillin, doxycycline if allergic

o   Has to be given through injection in the butt

§  Infection < 2 years old = 1 injection

§  Infection > 2 years old = 3 injections

- If you get treated, do you always have it?

o   NO

§  Bacteria not virus

o   You will always test positive in your blood for syphilis even if treated

Part of Herpesviridae family: enveloped, double stranded DNA viruses

mostly skin and mucous membrane lesions

o   HSV-1 = infections above waist

o   HSV-2 = infections below waist

most contagious when virus-filled lesions are present

o   Can also spread by asymptomatic shedding

§  Can be in saliva and genital secretions EVEN without lesions

o   Binds to epithelial cell receptors

§  Triggers them to internalize the virus

o   Once inside, starts lytic cycle

§  DNA gets transcribed and translated

·       Forms viral proteins -> more HSV virus

o   Can travel up the axon to cell body to start the latent cycle

o   Neurons in face have cell bodies in the trigeminal ganglia

o   Neurons in genitalia have cell bodies in the sacral ganglia

§  HSV settles in for LIFE

§  Neurons aren’t destroyed, they just become HSV permanent home

§  HSV makes copies of itself and sends it down axon

·       released + infect epithelial cells

·       happens throughout life

·       Risk factors

o   Stress

o   Skin damage

o   Viral illness

·       Recurrent episodes less severe

o   lesions develop on the same side as the affected ganglion

§  Trigeminal and sacral ganglia serve just one side of face/body

children

primary infection symptomatic, but after

§  Causes lesions, fever + enlarged lymph nodes

§  pharyngitis

reactivate is often symptomatic but can cause lesions at vermillion border

o   Primary infection can case ulcers and pustules

o   Reactivation often no symptoms

§  But can – fewer blisters and resolves in about a week

finger = hepatic whitlow

- finger rubs lesion

- easy to transfer to other body parts

trunk,extremeties, head = herpes gladiatorum

- common among wrestlers

burns or atopic dermatitis

eye = keratoconjunctivitis

- cornea blurred vision, dendritic lesion

- conjunctiva: pain, red, tearing, sensitive to light

CNS ( rare) = meningitis or encephalitis

- commonly happens with reactivations

- only affects frontal lobe

o   Causes 3 patterns of illness

§  1. Skin, eye, mucous membrane

·       Lesions pop up 1-2 wks after delivery

·       Typically at site of damaged skin

§  2. CNS infection

·       Lethargy, irritability

·       Seizures

·       2-3 weeks after delivery

·       Same lumbar puncture, CT, MRI, EEG findings as adults

§  3. Disseminated infection

·       Sepsis + failure of organs

o   How skin + mucous membrane lesions look

o   Confirmation

§  Look for viral DNA with PCR

§  Antibody response to virus

§  Growing virus in culture

Treatment

o   Often resolves without

o   Antiviral drugs -> reduce pain + speed up healing, best if taken at start of prodrome

§  Acyclovir

§  Famciclovir

§  Valacyclovir

o   High dose, IV antivirals for severe cases

contact infection

o   Virus stays in cells near point of infection – doesn’t spread throughout whole body

- often spread throughout sex

Body is able to eradicate most strains of HPV

o   HPV-6 and HPV-11 cause abnormalities in the cells of the infected tissue

§  Develop into genital warts

·       Are infectious + require topical cream Tx

·       no long term damage

o   HPV 16 and HPV 18

§  Cells in cervix are especially at risk

§  responsible for majority of cases of cervical cancer

·  Can take 20 yrs for cancer Sx to appear

o   This is why pap smears are regular -> looking for abnormal cells

vaccines for HPV 16 + 18