Week 12: OB/GYN & Genitourinary - Contraception, HRT, Erectile disorders, Incontinence/BPH Flashcards
Pathophysiology of female reproductive system
- Hypothalamus controls pituitary gland via GnRH (released in pulsate manner to maintain cycle)
- Pituitary gland then releases LH and FSH which stimulates ovaries to release progesterone and estrogen
- Menstrual cycle and pregnancy are tightly controlled by both positive and negative feedback loops between hypothalamus, pituitary, ovaries, eggs and uterus
Hormones of the female reproductive system
FSH
- Stimulates maturation of follicle in ovary
- Causes release of estrogen which peak right before ovulation
LH
- Stimulate luteal phase of ovulation and promote thickening of endometrium
- Cause release of progesterone which peaks just before mestruation
Progesterone
- Responsible for preparing endometrium for pregnancy
- Thickens in preparation for implantation
- If egg implants it keeps rising to keep endometrium thick
- If fertilization does not occur, drops rapidly which results in shedding of endometrium
See menstrual cycle diagram
Contraception
- Options (All)
- Options of hormonal contraception
Options
- Hormonal contraception
- Barrier methods
- Withdrawal
- Rhythm or fertility awareness methods
- Copper IUD
- Spermicide
Option of hormonal contraception
- Progestin only (POP)
- Combined oral contraception (COC)
- Levonorgestrel IUD
- Vaginal ring
- Medroxyprogesterone injection (depot)
- Etonogestrel implant
Hormonal contraception: POP/Minipill
- MOA
- Benefits
- Risks
MOA
- Thicken cervical mucus to stop sperm from entering cervix preventing fertilization
- Changes the endometrium to mimic non fertile points of menstrual cycle preventing implantation
- May suppress ovulation by stopping LH surge
Benefits
- Can be taken by those who cannot have estrogen
- Lower risk of blood clot than COC
- Relatively inexpensive
Risks
- Harder compliance
- Slightly less effective than COC
- Oral - affected by N&V and malabsorption disorders
- Higher risk of ectopic pregnancy vs COC
- Can be androgenic (acne, weight gain)
- Higher incidence of breakthrough bleeding than COC
Hormonal contraception: COC
- MOA
- Contraindications
- Benefits
- Risks
MOA
- Has progesterone and estrogen to give broad contraceptive coverage
- Inhibit ovulation (more effective than POP)
- Reduce receptivity of endometrium to implantation
- Thicken cervical mucus
Contraindication
- Breastfeeding
- Higher risk of clots/stroke/MI if smoker, overweight, high BP, valvular disease, history of clots/VTE/MI/stroke, >40/50
- History of breast or cervical cancer
- Patients suffering from migraine with aura
Benefits
- Higher efficacy that POP
- Easier compliance
- Progesterone used are less androgenic than POP
- Inexpensive
Risk
- Higher risk blood clots than POP
- Common causes headache and nausea
- Oral - affected by nausea and vomiting
- Taken every day
Hormonal contraception: Hormonal IUD
- MOA
MOA
- Contains only a progesterone
- Small device inserted into uterus
- Local effect - releases levonorgastrel in order to change endometrium to prevent implantation and thickened cervical mucus
- In some women it suppresses ovulation
Hormonal contraception: Vaginal ring
- MOA
MOA
- Contains estrogen and progesterone
- Thickens cervical mucus forming barrier to sperm passing through cervix
- Inhibits ovulation through negative feedback loop of both LH and FSH
Hormonal contraception: Depot injection
- MOA
MOA
- Contains progesterone
- Injected by doctor and creates depot of progesterone that is slowly released over 12 weeks
- Thickens cervical mucus to create barrier to sperm
- Change endometrium to prevent implantation
- Reliably suppresses ovulation (compared to POP)
Hormonal contraception: Contraceptive implant
- MOA
MOA
- Contains only progesterone
- Inserted subdermally in inner, upper arm every 3 yrs
- Thickens cervical mucus to prevent sperm entering through cervix
- Change endometrium to prevent implantation
- Reliably suppresses ovulation by suppressing LH surge
Emergency contraception
- Options
Used to prevent pregnancy after unprotected intercourse or failed contraception
Options
- Levonorgestrel tablet within 72 hrs (contains progesterone high dose)
- Ulipristal tablet within 120 hrs (contains progesterone receptor modulator)
- Copper IUD within 5 days
Pathophysiology of menopause
- Two stages
- Cease to ovulate
- Occurs naturally with age
- Produce lower amounts of progesterone and estrogen
Stages
- Peri menopause (start to decline in hormone levels)
- Menopause (menstruation stops)
- Post menopause (all eggs gone)
Causes of menopause
- Naturally with age
- Drug induced in some chemotherapy agents
- Hysterectomy/oophorectomy
- Primary ovarian insufficiency
Clinical presentation of menopause caused by drop in hormone levels of
- Estrogen
- Progesterone
- Testosterone
Estrogen
- Hot flush/tingling
- Loss of BMD
- Vaginal dryness/atrophy
- Fatigue
- Breast pain/tenderness
- Headache
- Weight gain/fat redistribution
Progesterone
- Hot flushes/tingling
- Vaginal dryness/atrophy
- Spotting
- Fatigue
- Breast pain/tenderness
- Headache
Testosterone
- Hair loss/thinning
- Altered mood
- Low libido
- Forgetfulness
Menopause hormone replacement therapy options
- Tablets - estrogen and progesterone available separately or as combined
- Patches - estrogen available separately or as combined
- Gel - Estrogen only
- Cream and tablets - inserted into vagina
- IUD - progesterone only
Menopause HRT: Tibolone
- MOA
- ADR
MOA
- Estrogenic activity on vagina, bone, thermoregulator centers in brain
- Progesterone activity on breast tissue and endometrium
ADR
- Abdominal pain/bloating/weight gain
- Vaginal bleeding/discharge
- Dizziness/migraine/nausea
- Stroke
- Possible increase in breast cancer and endometrial cancer
Menopause HRT: Tibolone
- Contraindications and cautions
Hepatic impairment
- Contra in severe impairment
Renal impairment
- No precautions
Contraindicated
- Hormone dependent tumor
- CVD
- Cease 4 weeks before surgery
Erectile dysfunction
- Primary
- Secondary
Primary (rare)
- Psychological factors (guilt, depression, anxiety)
Secondary
- Organic etiology (vascular, hormonal, neurological, structural)
- Psychological (anxiety, stress, mood disorder)
- Situational (place, partner, time)
Physiology of an erection
- Cavernosal arteries dilate, engorging corporal tissue with blood
- Engorging causes corporal tissue to swell, erecting penis
- Engorged corporal tissue compresses penile veins and venules, maintaining erection
Erectile dysfunction - Non pharmacological treatment
- Remove causative factors
- CBT/councelling
- Treat causative factors
Erectile dysfunction - Pharmacological treatment options
1st line
- Oral PDE-5 inhibitor
2nd live
- Intracavernosal alprostadil/vacuum device
3rd line
- Intracavernosal combination
4th line
- Penile implant
Erectile dysfunction: PDE-5 inhibitor
- MOA
- Examples
MOA
- Inhibit breakdown of cGMP to inactive GMP by PDE-5
- Allow increased vasodilation and relaxation of corpus cavernosum to increase blood flow during sexual stimulation
Example
- Sildenafil (Viagra)
- Tadalafil
Erectile dysfunction: PDE-5 inhibitor
- Contraindications and cautions
Elderly
- Risk of hypotension
- Require low dose - assess exercise tolerance
- Half life is increased
Hepatic impairment
- Low dose in mild/mod
- Do not use in severe
Renal impairment
- Low dose in moderate impairment
Contraindications
- Migraine
- NO donors
- CVD
- Leukaemia
- Sickle cell anaemia
Erectile dysfunction: Alprosadil
- MOA
- ADR
MOA
- Local injection
- Prostaglandin E1 analogue - dilates arteries in corpus cavernosum
- Relax smooth muscle of corpus cavernosum and spongiosum
ADR
- Penile pain
- Priapism
- Brusing/injection site reaction
- Fibrotic changes
- Hypotension/fainting/dizziness
Erectile dysfunction: Alprosadil
- Contraindications and cautions
Elderly
- Assess exercise tolerance
- Higher risk of orthostatic hypotension
Hepatic and Renal impairment
- No precautions
Caution
- Men with HIV/HepB/C
Contraindication
- Penile implant
- Anatomical deformities of penis
Priapism
- Definition
- Treatment
Definition
- Prolonged painful erection
Treatment
- 2 hrs = hot shower and pseudoephedrine 120mg (cold and flu vasoconstrictor)
- 2-4 hrs = repeat previous treatment and phone doctor
- >6 hrs = hospital to aspirate and drain corpora cavernosa, infusion of adrenergic drug to contract smooth muscle
If aspirate not successful a surgical stunt required
Types of urinary incontinence
- Urge incontinence
- Bladder over sensitivity from infection or neurological disorders - Stress incontinence
- Reduce pelvic floor
- Increased abdominal pressure (pregnancy) - Overflow incontinence
- Urethral blockage
- Bladder unable to empty properly
Urinary incontinence - risk factors
- UTI
- Menopause
- Obesity
- Constipation
- Neurological/ musculoskeletal conditions
- Diabetes
- BPH
- Pregnancy/vaginal delivery
- Medication
- Advanced age
Urinary incontinence - management
- Non pharmacological options
- Bladder diary
- Manage underlying contributing factors
- Pelvic floor exercises/bladder training
- Schedual voiding
- Incontinence pads
Urinary incontinence - management - Pharmacological options 1st line = anticholinergics - MOA - Example - ADR
1st line = Anticholinergics
MOA
- Block cholinergic receptors on bladder to reduce contractility and increase bladder capacity
Example
- Oxybutynin
- Solifenacin
ADR
- Confusion
- Constipation
- Dry mouth
- Blurred vision
- Urinary retention
- Drowsiness
- Dizziness
Urinary incontinence - management
- Pharmacological options
1st line = anticholinergics
- Contraindications and cautions
Elderly
- More likely to experience ADR
- Start low and go slow
Hepatic impairment
- Reduce dose
Children
- Prefer oxybutynin
- Can be used from age 5
Pregnancy and breastfeeding
- Limited data
- See specialist
Renal impairment
- Reduce dose
Caution
- Those with urinary overflow secondary to urinary retention
- Bladder outlet obstruction
- Avoid combination with other drugs that have anticholinergic effects
Urinary incontinence - management - Pharmacological options 2nd line = Desopressin - Indication - MOA - ADR
Indication
- Nocturnal enuresis in children 5 and over
- Available as oral spray and wafer
MOA
- Bind to V2 receptor in collecting duct of nephron
- Increases amount of water reabsorbed from urine back into kidney
ADR
- Hyponatremia/fainting/seizure/coma
- Nasal irritation/nausea
Urinary incontinence - management
- Pharmacological options
2nd line = Desopressin
- Contraindications and caution
Elderly
- Not indicated for
Children
- Oral tablets and wafers preferred to spray due to increased risk of hyponatremia with spray
Caution in children who cannot comply with fluid restrictions
Urinary incontinence - management - Pharmacological options 2nd line = Mirobegron - MOA - ADR
For adults and can take up to 8 weeks to see effect
MOA
- Beta3 receptor agonist on bladder muscle
- Relax bladder muscle as it fills and increases bladder capacity
ADR
- Increased BP
- UTI
- Headache
- Tachycardia
Urinary incontinence - management
- Pharmacological options
2nd line = Mirobegron
- Contraindications and caution
Elderly
- More likely to see hepatic/renal/HT/arrhythmia effect
- Start low and go slow
Hepatic impairment
- Low dose for mode impairment
- Avoid in severe impairment
Children
- Not indicated
Pregnancy and breastfeeding
- No data; avoid if possible
Renal impairment
- Reduce dose
- Do not use in severe impairment
Caution
- Hypertension
- Severe uncontrolled HT or arrhythmia
Benign Prostatic hyperplasia/hypertrophy
- Size of prostate
- Prostate generally gets larger over time
- Exact cause of BPH is unknown
- Size of prostate directly linked to testosterone
- As it enlarges it narrows urethra and puts pressure on bladder
BPH symptoms and presentations
Lower urinary tract symptoms (Voiding or obstructive)
- Hesitancy
- Weak and poorly directed stream
- Straining to urinate
- Dribbling after urination has finished or irregular stream
- Urinary retention
- Overflow or paradoxical incontinence
Lower urinary tract symptoms (storage or irritative)
- Urgency
- Frequency
- Nocturnal
Other symptoms
- Perineal pain
- Dysuria
- Haemoturia
BPH
- Diagnosis
- Treatment options
Diagnosis
- Blood test for PSA
- Physical exam for DRE
Treatment options - No treatment - Oral medicines > Alpha blockers > PDE-5 inhibitors > 5-alpha reductase inhibitors - Surgery > Transurethral resection of prostate > Transurethral incision of prostate > Open or retropubic prostatectomy - Laser treatment
BPH pharmacological treatment - 5-alpha reductase inhibitor
- MOA
- Example
MOA
- 5-alpha reductase is enzyme which converts testosterone to dihydrotestosterone (more potent and stimulates prostate growth)
- Results in reduced size of prostate allowing better urinary flow
Example
- Dutasteride
- Finasterise
BPH pharmacological treatment - 5-alpha reductase inhibitor
- Contraindications and cautions
Elderly
- Caution with fixed combination dutasteride and tamsulosin due to increased risk of hypotention
Children
- Not indicated
Pregnancy
- Caution - should not handle capsules or tablets
BPH pharmacological treatment - Selective alpha blockers
- MOA
- Examples
MOA
- Selectively block alpha 1 receptor
- Relaxes smooth muscle of bladder neck and prostate which results in decrease in resistance to urinary flow
Example
- Tamsulosin
- Prazosin
BPH pharmacological treatment - Selective alpha blockers
- Contraindications and cautions
Elderly
- Avoid prazosin
- Use other options with caution
- More susceptable to orthostatic hypotension
Hepatic impairment
- Contraindicated with alfozosin
- Caution with use of other options
Children
- Not indicated
Renal impairment
- Worsened first dose hypotension; begin treatment cautiously
Caution
- Patients already on anti hypertensives due to risk of hypotension
UTI classification
- Types
- Uncomplicated
- Complicated
Types
- Cystitis = infection of bladder
- Urethritis = infection of urethra
- Epididymitis = infection of epididymis
- Pyelonephritis = infection of kidney/upper urinary tract
Uncomplicated
- Premenopausal
- Non-pregnant
- Adult women with no structural/functional abnormality
- Recurrence = within 2 weeks of 1st infection
- Reinfection = > 2 weeks from 1st infection
Complicated
- Not uncomplicated
- Chronic recurring
- Children
- Pregnancy
- Anatomical/functional abnormality
- Comorbidities
UTI risk factors
- Female
- Sexual activity
- Age
- Immunosuppresant
- Genetic
- Catheter use
- Dehydration
- Pregnancy
- Diabetes
- Antibiotic use
- Inability to completely void bladder (paralysis or stroke)
UTI Pathophysiology
- Upper urinary tract and bladder are normally sterile
> Opening to these tracts are not
> Bladder normally clears itself by completely voiding urine
> Acidity of urine helps kill bacteria
Infection of upper urinary tract - kidney causes easy hematogenous spread to surrounding tissue and sepsis and shock can occur quickly
UTI presentation/symptoms
- Common/uncomplicated adult
- Pyeloephritis
- Elderly
- Children under 2
Common/uncomplicated adult
- Dysuria
- Increased frequency
- Urgency
- Suprapubic pain
- Hematuria
Pyelonephritis
- Fever/chills
- Pain in back/lower abdomen
Elderly
- Often asymptomatic
- Confusion
- Loss of appetite
- Flu like symptoms
Children under 2
- Often non specific
- Fever
- General unhappiness/failure to thrive
- Loss of appetite
- Abdominal pain
- Vomiting
UTI complications if untreated
- Recurrent infection
- Permanent kidney damage
- Pregnancy - low birth weight or premature birth
- Urethral stricture (male)
- Sepsis - death (common in elderly)
UTI diagnosis
- Urine sample
- CT/MRI (if anatomical abnormality suspected)
- Cytoscopy (visualize tract and bladder)
UTI treatment
- Non pharmacological
- OTC/Herbal
Non pharmacological
- Drink fluid
- Avoid acidic drink and caffeine
- Heating pads
OTC/Herbal
- Urinary alkaliniser - symptomatic relief
- Cranberry
- Hexamine hippurate
UTI treatment
- Antibiotics (general info)
Antibiotic resistance is growing
- Keep course short as possible
If asymptomatic only treat children and pregnant women
UTI treatment
Uncomplicated UTI
- Antibiotics
> Examples
Antibiotics
- Short term
- Oral
Example
- Trimethoprim (3days)
- Cephalexin (5days)
- Amoxycillin + clavulanate (5 days)
UTI treatment Complicated UTI - Pregnant - Men - Pyelonephritis (mild) - Pyelonephritis (severe)
Pregnant
- Same as uncomplicated but no trimethoprim
Men
- Same as uncomplicated but all for 7 days
Pyelonephritis (mild)
- Same as uncomplicated but for 10-14 days
Pyelonephritis (severe)
- IV antibiotics
UTI treatment for recurrent UTI
Long term treatment
- Trimethoprim oral daily for 3-6 months
OR
- Cephalexin oral daily doe 3-6 months
If sexual intercourse is cause can use antibiotic when sex occurs rather than daily
