Repro pathophys: Aging, Menopause Flashcards
1
Q
physiology menopause
A
- follicular decline
- d/t ovulation and *apoptosis of non ovulated follicles, ovarian reserve undetectable by ~50 y/o
- apoptosis of oocytes accelerates ~35 y/o (~25000 starting point at this age) - AMH decline
- AMH is produced by granulosa cells; no follicle = no granulosa cells = no AMH
- undetectably ~5 yr before menopause
- – irregular cycles begin around this time
- AMH levels predictive of ovarian reserve - estradiol (E2) decline
- E2 is produced by dominant follicle; no ovulation/dominant follicle = no estrogen from ovary
- still have estrogen formed at peripheral fat (and other sites) from androgen conversion
- – aromatase inhibitors used in breast cancer treatment inhibit this process = even lower estrogen - FSH increases
- d/t ovarian failure
2
Q
dx menopause
A
clinical: cessation of menses for 12 mo at appropriate age (~48-51) or with no other identifiable cause
surgical: d/t bilateral oophorectomy
3
Q
stages of menopause
A
- early perimenopause
- middle perimenopause
4
Q
early perimenopause
A
- 2-8 yr pre-end of menses
- shorter follicular phase
- higher FSH
sx:
- short-to-normal cycle lengths
- hot flashes
- interrupted sleep
- breast tenderness
- may be asymptomatic (aside from cycle changes)
5
Q
middle perimenopause
A
- variable pre-menopause
- unpredictable cycle pattern
- some ovulatory, some anovulatory cycles
- during anovulatory, estrogen rises and falls w/o progesterone
- FSH even higher
sx:: irregular periods - short cycles w/ mixed amenorrhea vasomotor: - hot flashes - interrupted sleep - breast tenderness - dysphoric mood - depression - mild memory problems GU atrophy -- worsens over time - dyspareunia (pain during sex) - atrophic vaginitis - dysuria - urinary urgency/incontinence - may be asymptomatic (aside from cycle changes)
6
Q
late perimenopause
A
- first year post-menopause (FMP)
- FSH high
- same sx as middle perimenopause
7
Q
post menopause
A
- 1+ yr post-FMP
- sx improve
8
Q
indications for hormone tx menopause
A
- osteoporosis/frax risk
- symptomatic menopause
otherwise not indicated
- strokes, blood clots, breast cancer increase (cancels out any benefit related to heart disease or osteoporosis, except when high risk)
- does not improve well-being unless sx
9
Q
epidemiology menopause sx
A
more likely, longer in
- smokers
- black
- latina
- high BMI
10
Q
hot flashes/vasomotor sx mx
A
- abrupt drop in sex steroids e.g. menopause, GnRH AG/aNTagonists
- pituitary insufficiency e.g. hypophysectomy, primary insufficiency
- can also occur in men experiencing drop in sex steroids e.g. prostate cancer tx
mx:
- estrogen causes inhibition of thermoregulatory center of hypothalamus
- estrogen removal increases serotonin, 5-HT sensitivity in hypothalamus
- others
11
Q
vasomotor menopause sx primary tx
A
tx:
- hormone therapy ~80-90%
- oral, transdermal, vaginal
- estrogen + progestin
- progestin essential to prevent uterine cancer if uterus is present (frequency of hyperplasia ~35% otherwise)
- note that there is an increase in breast cancer in estrogen + progestin vs estrogen only, but this is outweighed by risk of uterine cancer in general (obvious exceptions)
- lowest dose for shortest period of time possible
c/i:
- hx breast cancer
- CHD
- VTE/stroke/TIA
- liver disease
- unexplained vaginal bleeding
- endometrial cancer
12
Q
vasomotor menopause sx alternate tx
A
- gaba
- SSRIs
- SNRIs
- clonidine
- general healthy lifestyle choices (reduced smoking, drinking, diet, exercise)
complementary: similar to placebo, which is 25-50% reduction
- dong quai
- red clover
- black cohosh
- yam progesterone
- ginseng
- acu
13
Q
surgical menopause sx tx in transmen
A
research limited, case studies show incorporation of transdermal estrogen in addition to testosterone did not affect masculinization
as w/ physiologic menopause, may be asymptomatic
14
Q
vulvar/vaginal atrophy sx, mx
A
sx:
- burning
- dyspareunia (pain during sex)
- UTI
- itching
*chronic, requires lifelong tx
mx:
- reduced estradiol –> reduction in superficial cells
- increase in parabasal cells
- increased vaginal pH (acid –> base)
15
Q
vulvar/vaginal atrophy tx
A
- local estrogen
- note recent RTC show that systemic estrogen not helpful
16
Q
“non-genital” h&p sexual dysfunction in F
A
- pt description of problem, OLDCAARTS
- systemic disease ROS
- disabilities
- body image
- stress, fatigue, mood
- intimacy, partner effects
- sexual stimulation
- how partner(s) is/are reacting
- others vs self-stim
- penetration vs toys vs oral, manual
- hx abuse
17
Q
“genital” h&p sexual dysfunction in F
A
- gyn sx
- dryness, discharge
- bleeding
- pain
- itching, burning
- STI risk
pelvic exam
- external
- introitus
- internal
- bimanual
18
Q
sexual dysfunction tx in F
A
- treat identifiable disorders
- psychological (if applicable, for causes or effects)
- drugs overall unhelpful unless identifiable cause incl gyn condition, systemic, drug side fx
- d/c offending drugs if possible
NOT helpful:
- sildenafil, except +SSRI
- systemic estrogen
- yohimbine
- DHEA
minimal benefit:
- testosterone
- flibanserin
- bremelanotide
- bupropion
19
Q
nerves involved in sexual response F
A
autonomic
- *parasympathetic, pelvic splanchnic
- – inferior hypogastric S2,3,4
- some symp, sacral splanchnic
- – lower T and upper L
motor/sensory
- pudendal nerve S2,3,4
20
Q
drugs associated with reduced libido
A
SSRIs nicotine chronic alcohol opioids OCPs (mixed data) benzos antipsychotics
21
Q
health conditions associated with reduced libido
A
HTN, possibly tx related MS PD pain CKD hypER-T4 hypER-prolactin DM (mixed data) cancer, post-cancer depression anxiety (may also favor increased libido)
RTC show testosterone levels not related but exogenous may increase desire slightly
22
Q
dysparuneia ddx
A
superficial:
- vestibulodynia
- vulvodynia
- chronic vulvar dermatoses
- condylomas
- derm
deep:
- endometriosis
- pelvic congestion syx
- interstitial cystitis
- uterine retroversion
- uterine leiomyomas
- adenomyosis
- PID
- pelvic adhesions
- ovarian remnant syx
- IBS
- hx sexual abuse
23
Q
most significant predictor of sexual activity in older women
A
available partner
24
Q
bartholins gland enlargement
A
ddx abcess vs cyst
rarely: benign or malignant tumor (carcinoma)
- dilation d/t duct obstruction ± infection
- abscess more common than cyst
- common in young pre-menopause and peaks around menopause
- nk risk fx
25
bartholins gland cyst
clinical:
- unilateral enlargement visible and palpable at 4 or 8 o'clock of vestibule
- 1-3 cm average
- usually painless
tx:
- watch and wait, small asymptomatic
- warm compress
- analgesis
- if larger/symptomatic, I&D or word catheter
- if persistent:
- - marsupialization
- - excision of entire cyst
- - consider biopsy, malignancy (esp in older ppl)
26
barholins gland abscess
```
clinical:
- soft, painful mass
- difficulty walking or sitting
- 3-6 cm average
fluctuant, warm ± erythema
```
path:
- usually E. coli
- MRSA, strep also possible
tx:
- I&D
- culture
- word catheter
- abx
- pain
27
vulvovaginal candidiasis
sx:
- itching
- thick, white, cheesy discharge
exam:
- labial erythema
- edema
- white discharge
- normal ~4.5 pH
- hyphae on wet mount
path:
- usually Candida albicans
tx:
- azoles
- oral: fluconazole 150mg x1
- vaginal: clotri-, mico-, terconazole
don't fall into trap of presumptive dx
28
vulvar lichen sclerosus
- derm
- benign but can lead to vulvar neoplasm
sx:
- vulvar itching, pain
- - intense, disrupts sleep
- dyspareunia
- ± perianal involvement
exam:
- white, thinned, crinkled epithelium
- labia majora and minora involvement
- ± perianal involvement - hourglass configuration
- loss of skin architecture over time
- ± thickening over time
- majora/minora fusion
- narrowing of introitus
dx:
- vulvar punch biopsy
- exam
mx:
- epithelia thinning ± thickening
- inflammation
- associated w/ low estrogen
- genetics, autoimmunity, local factors, hormonal factors ...
epi:
- peaks pre-pubertal and peri/post menopausal
- rising incidence
tx:
- topical steroids BID x 1 month --> 2ce weekly maintenance tx
- minimize irritants
- break itch/scratch cycle
- petrolatum
- yearly f/u one controlled
- watch for malignancy
- hormonal therapy NOT helpful
29
vulvar contact dermatitis
- irritant or allergic
- allergic more severe, vesicular
sx:
- burning
- stinging
- swelling
- pain
- pruritus
exam:
- erythema
- edema
- thickening
- hypOpigmentation
common irritants:
- scented soaps and detergents
- iodine
- pads
- wipes
- bodily secretions
- spermicides
- deodorants, perfumes
tx:
- remove irritant
- break itch/scratch cycle
- short course topical steroids
- topical petrolatum
- soon soaks
- cold packs
- avoid tight clothing and friction
breaking itch/scratch cycle:
- education
- cutting fingernails
- wearing soft gloves, underwear at night to avoid inadvertent scratching
- topical petrolatum
- pressure vs scratching when itchy
30
vulvar itching ddx
most common:
- candidiasis
- contact dermatitis
can't miss:
- lichen sclerosus, risk of carcinoma if untreated
- squamous cell carcinoma
- melanoma
- vulvar biopsy indicated if pigmented lesions, masses, raised, ulcerated, eroded, recurrent
also:
- psoriasis
- atopic dermatitis
- hidrandenitis supperativa
- infection
- lichen simplex chronicus
- lichen planus
31
tunica albuginea
surrounds corpora cavernosa
| provides rigidity for erection
32
penile fracture
disruption of tunica albuginea
33
artery of tumescence
cavernous artery
34
main arterial source to penis
internal pudendal artery
35
subtunical venous plexus
between tunica albuginea and sinusoids
| collapsed during erection to maintain rigidity
36
nerves of erection
cavernous nerves
S2,3,4 (keep your penis off the floor...) parasympathetics (erection)
T11,12, L1,2 sympathetics (emission)
S2,3,4 sensory/motor (ejaculation)
37
cavernous nerves and prostate
posterolateral
| spared during nerve-sparing prostatectomy (to preserve erection)
38
psychogenic and reflexogenic erection
psychogenic
- non-genital stimuli
- S2,3,4 parasympathetic
- affected by stress/anxiety preventing erection
reflexogenic
- genital stimuli
- S2,3,4
- preserved in upper spinal cord injury, though may have incomplete sensation
39
physiological events of erection
- dilation of arterioles via relaxation of smooth muscle, increased blood flow (*nitric oxide)
- trapping of blood by expanding sinusoids
- compression of subtunical venous plexuses, less venous outflow
40
nitric oxide signalling in erection
- parasympathetics release NO
- NO --> guanylate cyclase activation = GTP --> cGMP
- cGMP closes calcium channels
- calcium sequestration --> relaxation of smooth muscle
41
detumescence physiology
- NE from sympathetics --> alpha adrenergic activation on smooth muscle
- --> elevation of intracellular calcium
- --> smooth muscle contraction
- --> narrowing of arterioles
- --> less engorgement --> less venule compression
42
ED risk fx
- age
- DM
- CVD
- psych
- smoking
- hypogonadism
43
types of ED
organic
- arterial
- cavernosa
- neurologic
- hormonal
- systemic disease
- drugs
psychogenic
- stress, anxiety
- strained relationship, lack of sexual interest in partner
- depression
- d/t excess sympathetic outflow
mixed
- ~90%
44
neurogenic ED
- ~10-20%
- CNS or PNS pathology
CNS
- damage to integration centers for sexual drive
- -- hippocampus, hypothalamus, preventricular nucleus
- -- CVA, epilepsy, encephalitis, trauma
- dopaminergic pathway damage
- -- PD, AD, dementias
- spinal cord injury
PNS
- cavernous, pudendal nerve
- DM, pelvic radiation, surgery, radical prostatectomy
- in DM, endothelial damage limits NO synthase
45
hormonal ED
- hypOgonadism, testosterone
- hypO or hypER thyroidism
- hypERprolactinemia
testosterone:
- generally d/t aging
- T decreases ~.8%/yr starting mid-30s
- sharp increase in ED when T <300
- maintain nocturnal erection when T >200
- testosterone & DHT relax penile artery and cavernous smooth muscle
- T increases sexual drive
prolactin
- high prolactin --> GnRH suppression --> low T
46
arteriogenic ED
- generally part of systemic arterial disease
- -- htn, hld, dm, obesity, atherosclerosis, smoking
* often an early symptom of systemic arterial disease, can tip off to impending worsening
- -- penile arteries smaller than coronary arteries
- -- signs of plaque formation show up sooner
- -- CVD screening in young men w/ organic ED
47
venoocclusive ED
- venous leak
- outflow = cannot maintain erection
- d/t insufficient smooth muscle relaxation, inadequate sinusoidal expansion, and insufficient compression of subtunical venules
48
drug-induced ED
psychotropics
- interfere w/ dopaminergic, serotonergic, non-adrenergic pathways
- bupropion addition often effective for reversing ED associated w/ psychotropics
- associated w/ SSRI, MAOI, TCA, antipsychotic usage
anti-hypertensives
- beta blockers
- ACE-I
- ARBs
- diuretics
- Ca++ blockers
anti-androgens
- 5 alpha reductase inhibitors
- ADT for prostate cancer
- opioids
- ketoconazole
- cimetidine
49
ED hpi
- morning erections?
- masturbation?
- all partners?
- stressors?
- new meds?
- pelvic surgery?
- systemic?
50
ED exam
- fibrosis?
| - testicles firm/soft?
51
ED labs
morning testosterone
TSH/T4
(prolactin)
(CVD workup if risk)
52
ED tx
- lifestyle
- psychotherapy ± sex therapy
- restore T >300
- change offending meds where applicable/feasible
- phosphodiesterase 5 inhibitors e.g. viagra
- intracavernosal injection
- MUSE (medicated urethral system for erection) = PGE1 pellet inserted to urethra, stimulates adenylyl cyclase
- penile prosthesis (has pump bulb in scrotum, reservoir near bladder, cylinder in penis)
53
PDE-5 inhibitors
- prevent cGMP --> GMP (detumescence)
- sexual stimulation still required to initiate erection
e. g.
- sildenafil (viagra)
- vardenafil (levity)
- tadalafil (cialis)
- avanafil (stendra)
c/i
- NAION (non-arteritic anterior ischemic optic neuropathy)
- angina during sex
- nitro use
sfx
- headache
- nasal congestion
- flushing
- blue visual hue
- diplopia, blurred vision d/t cr w/ PDE6
54
intracavernosal injection
- 1st line for PDE5i nonresponders
- ~85% effective in that population
adv:
- rapid onset
- reduced systemic side effects
- dependable efficacy
disadv:
- self injection into penis
e. g.
- alprostadil
- papaverine
- phentolamine
55
peyronie's disease
- fibrous plaque --> curved erection
- scar tissue of tunica albuguinea
- any direction
- pain for pt or partner, psych distress
risk fx:
- penile trauma
- connective tissue disorders e.g. dupuytren's contracture, plantar fasciitis
tx:
- penile traction
- plaque excision and graft
- plication
- clostridium collagenase histolyticum injections
56
FSH stims ... to produce ... (M)
Sertoli cells, testicle
| nutrients for spermatogenesisyd
57
LH stims ... to produce ... (M)
leydig cells, testicle
| testosterone
58
T bioavailability
when weakly bound or free
| majority of T is bound to SHBG and is not bioavailable
59
SHBG
sex hormone binding globulin
binds T, inactive
increases w/ (binding T):
aging
cirrhosis
hypER-T4
decreases w/ (freeing up T):
diabetes
obesity
steroid use
60
DHT
dihydroxytestosterone
more potent metabolite of testosterone
T-->DHT via 5 alpha reductase
61
estrogen (M)
T-->estrogen via aromatization
| occurs in fat and Sertoli cells (the ones that make nutrients for the sperm)
62
T circadian
diurnal
highest 7-9am
decreased variation b/w 6am and 2pm w/ age
63
low T sx
sex:
- low libido
- decreased spontaneous erection
* ED
* diminished PDE5i response
general
* low energy, fatigue
- diminished sense of vitality, well-being
* depressed mood
- irritability
- impaired cognition
- reduced motivation
physical/metabolic
* increased CVA risk
* decreased bone mineral density, frax risk
- decreased muscle mass/strength
- increased body fat
- gynecomastia
- reduced testicular size and firmness
- anemia
- insulin resistance
64
low T dx
T labs 7-9am
recheck if low
<300 ng/dL
then order
* LH
FSH
prolactin
CBC - Hgb and hct - T causes erethrocytosis, anemia can occur when low
if T >40, check PSA (T replacement will raise PSA)
65
low T tx
exogenous T
c/i
- PSA high
- preserving spontaneous fertility
- alternative tx if c/i: intranasal HRT, SERMS e.g. climid, hCG
safe re:
- prostate cancer
- adverse cardiac events
- VTE
help w/
- BMD
- ED
- libido
- anemia
- lean body mass
- depressive sx
inconclusive
- cognition
- diabetes
- energy/fatigue
- lipids
- QoL
66
T insurance coverage
medicare- IM/SQ TRT
| commercial- all
67
T therapy w/ LE edema
- avoid T cypionate
| - use T enathate
68
T therapy w/ high baseline Hgb/Hct or secondary polycythemia
- avoid IM TRT or use lower dose
- instead use topical, intranasal, or sub-Q T
- note topical c/i if concerns about transferrence
- serial phlebotomy also an option
69
xyosted
- sub-Q autoinjector T
- less (usually no) pain on injection
- less likely to develop polycythemia
- covered by medicare
70
T therapy w/ elevated estrogen
- avoid high-dose IM b/c high peaks when converted by aromatase --> E can result in gynecomastia
- common concern in transmen
- may also/instead add an aromatase inhibitor
71
long-acting T options
- testopel pellets, placed in office q3-6 mo
| - aveed, long-acting IM q10 wk
72
topical T c/i
- transference concerns (sticks on clothing, may get on other stuff in wash, touching people etc)
- sensitive skin
73
injectable T c/i
- blood thinners/bleeding tendency
74
GU innervation - symp
- symp post
- T10-L2
- lower lumbar ± sacral splanchnics (≠ pelvic splanchnic, which are para)
- inferior hypogastric plexus
75
GU innervation - para
- para pre
- S2,3,4
- pelvic splanchnic nerves (≠ sacral splanchnic, which are symp)
- inferior hypogastric plexus
76
GU innervation - somatic
somatic
- pudendal nerve
- passes b/w piriformis and ischiococcygeus
- motor innervation to external sphincters of bladder and anus, erectile bodies
- sensory innervation from external genitalia, perineal skin
- S2,3,4
77
onuf's nucleus
- distinct group of neurons
- ventral anterior horn of sacral spinal cord
- micturition, defecation, muscle contraction of orgasm
78
micturition in paraplegia
- still have reflex micturition
- no motor control
- since both are important, incomplete voiding is a concern
- may need indwelling catheter
79
neurotransmitters of micturition
NE
- adrenergic alpha-1 on bladder neck and urethra
- beta-3 on detrusor
ACh
- M2 and 3, detrusor
NO
- also involved in relaxation of smooth muscle
80
CNS center of micturition
pontine micturition center (PMC)
pontine storage center (PSC)
spinobulbospinal reflexes
81
stress urinary incontinence
SUI
involuntary urine loss d/t increased abdominal pressure (coughing, sneezing, laughing, exercising)
no bladder contraction
no urge to void
usually small amount of urine
often d/t weakened pelvic floor e.g. in setting of multiparous women (insufficient pressure closing urethra)
*increased risk of bladder, uterus, and rectal prolapse into vaginal area d/t weak pelvic floor
tx:
- PT e.g. kegels
- biofeedback kegels
- timed voiding/bladder retraining
- lifestyle e.g. caffeine, alcohol reduction
- intravaginal urethral compression devise
- occlusive devise
- surgery
rx:
- little clinical benefit
82
urge urinary incontinence
```
overactive bladder (OAB) - now and often
overactive detrusor - involuntary bladder contractions
variable amount of urine dep on sphincter fx
```
see also:
- nocturia - waking multiple times at night to pee
- enuresis: involuntary urination, esp in kids at night "bedwetting" - delayed maturation of micturition
tx:
- mirabegron, beta3 adrenergic AGonist relaxes smooth muscle
- oxybutynin - muscarinic AGonist
- tolerodine - muscarinic AGonist with more "bladder selectivity" i.e. less effect on salivation
- BoNTs
83
functional urinary incontinence
d/t mental or physical disability
unwilling or unable to reach toilet when needed
e.g. PD, AD, severe depression
84
distribution of types of UI
stress ~43%
urge ~21%
mixed ~35%
in otherwise (mostly) healthy population i.e. when functional UI does not apply
85
pH of semen
alkaline
vagina is acidic so this protects sperm
seminal vesical alkalizes
86
BPH
- histology dx
- proliferation of glandular epithelium and smooth muscle in transitional zone of prostate, which surrounds urethra
- affects ~50% over 60 and ~80% over 80 d/t gradual enlargement of prostate after ~40 y/o
sx:
- incomplete voiding d/t obstruction
- urinary frequency
- urgency
- nocturia
tx::
alpha 1 receptor antagonists relax prostate and bladder neck smooth muscle
- e.g. *tamsulosin, other -zosins
- sfx: orthostatic hypotension, runny/stuffy nose, ejaculation problems
5-alpha reductase inhibitors --> prostatic atrophy by inhibiting T-->DHT
- finasteride (5-alpha reductase type 2)
- dutaseride (type 1 and 2), near complete suppression of serum DHT
- sfx: low libido, ED, ejaculatory dysfunction, depression
PDE5 inhibitors promote smooth muscle relaxation (improves voiding and tx ED)
- tadalafil (cialis) preferred d/t longer t1/2
87
ddx urinary retention
```
BPH (M)
diabetic neuropathy
urethral stricture
low spinal cord injury
pelvic prolapse (F)
MS
drugs
```
acute:
- painful, palpable, percussable
- unable to pass any urine
chronic:
- nonpainful
- palpable, percussable post-void
- overflow incontinence
- high post-void residual volume (US)
88
drugs for urge incontinence
goal: relax overactive detruser
- muscarinic antagonists oxybutynin, tolterodine
- beta-3 adrenergic AGonist mirabegron
89
drugs for stress incontinence
generally ineffective
kegels, biofeedback, etc.
possible surgery (pelvic floor reconstruction)
90
drugs for functional incontinence
tx underlying disorder where possible
drugs that act directly on bladder don't help b/c no organic dysfunction
catheters
91
drugs for overflow incontinence
i. e. incomplete voiding, BPH
- tamsulosin - alpha-1 receptor agonist - relax smooth muscle in prostate and urethra
- finasteride, dutasteride - 5-alpha reductase inhibitors - suppress DHT, shrink prostate
- tadalafil (cialis) - PDE5 inhibitor - relaxes smooth muscle
92
drug-induced urinary retention
sx:
- incomplete voiding
- frequent urination, small amounts
- urinary hesitancy (difficulty starting flow)
- slow urine stream
- urgency without urination
- feel need to urinate after urinating
offenders:
- muscarinic ANTagonists:
- -- antipsychotics
- -- antidepressants
- -- anticholinergic respiratory
- opioids
- alpha adrenergic receptor AGonists
- benzos
- Ca++ channel ANTagonists
- anesthetics
