Menopause Flashcards
How is menopause defined?
Permanent cessation of menses after 12 months
*Occurs due to loss of ovarian follicular activity (ovaries less responsive to gonadotropins, less E and P secreted, low levels of circulating E cause removal of negative feedback on hypothalamus and pituitary)
What are the 2 etiologies of menopause?
- Natural
- occurs in stages including perimenopause, menopause, postmenopause - Induced
- due to removal of both ovaries or iatrogenic ablation of ovarian function (e.g., chemotherapy, pelvic radiation)
- occur before natural menopause
What are the different changes that occur from perimenopause, menopause to postmenopause?
- Changes in menstrual cycle
- variable length persistent >=7 day difference in length of consecutive cycles
- interval of amenorrhea >= 60 days
- Changes in supportive criteria during menopausal transition
- FSH increases (higher than normal)
- Stabilizes when reach menopause
- Symptoms
- Vasomotor symptoms more likely first
- Followed by urogenital atrophy symptoms
What are the common broad clinical presentation/symptoms of menopause transition?
- Vasomotor symptoms
- Genitourinary syndrome of menopause (GSM)
- Psychological/cognitive
- Bone fragility
Describe the Vasomotor symptoms, and its MOA
Most notably: hot flushes and night sweats
- Intense feeling of heat on face
- Rapid/irregular HR
- Flushing/reddened face
- Perspiration
- Cold sweats
- Sleep disturbances
- Feeling of anxiety
Others: itchy and dry skin, hair loss, brittle nails, digestive problems, breast pain
*Can occur several times a day
MOA: thought to be due to thermoregulatory dysfunction, initiated at the level of the hypothalamus by estrogen withdrawal
Describe the Genitourinary symptoms, and its MOA
GSM
- Genital dryness
- Burning/irritation/pain
- Sexual symptoms of lubrication difficulty
- Impaired sexual function/libido/painful intercourse
- Urinary urgency
- Dysuria
- Recurrent UTI
- Frequent urination and urinary pain
MOA: low levels of Estrogen, cause vagina to lose collagen and fat deposits, lose water and become thin and dry, thus cause changes to labia, clitoris, vestibule, vagina, urethra, bladder
*Eventually vagina narrows and shortens
Describe the psychological/cognitive symptoms
- Depression/Anxiety
- Poor concentration/memory
- Mood swings
*Can also be multifactorial - due to stress, hormonal fluctuations
Describe how menopause transition results in bone fragility
Low levels of estrogen cause more bone loss/break down => incr risk of osteoporosis, fractures, joint pains
(E regulates bone metabolism and promotes activity of osteoblast to make new bone)
Menopausal symptoms are largely attributed to _____, hence pharmacological treatment involves _________
Estrogen deficiency
Hormone Replacement Therapy
What non-pharmacological can be used to treat mild vasomotor symptoms?
- Layered clothing that can be removed or added as necessary
- Lower room temp
- Less spicy food, caffeine, hot drinks
- More exercise
- Dietary supplements (conflicting)
*Isoflavones
=> Plant-based compound, phytoestrogen
=> Found in soybeans, legumes (lentils, chick pea)
*Black Cohosh
=> Herb native to North America
=> No significant DDI
=> Good evidence for vasomotor symptoms such as hot flushes, night sweats, palpitations
=> Possible serotonergic activity at hypothalamus
What non-pharmacological can be used to treat mild vulvovaginal symptoms?
Non-hormonal vaginal lubricants or moisturizers
When should HRT be initiated?
List the situations in which HRT should NOT be used solely for
HRT used for moderate/severe symptoms or insufficient response to non-pharmacologicals
HRT should not be used solely for:
- Treatment of low libido
- CVD prevention
- Depression/Anxiety/Cognitive/Memory issues
- Itchy skin
- Hair loss
- Treatment of osteoporosis (though it can be used for prevention)
HRT can consist of Estrogen only or Estrogen + Progestin.
Explain the use of Progestin.
Progestin is added on for patients with intact uterus to protect the endometrium from overgrowth (causing risk of endometrium cancer)
Some data that Progestin can improve vasomotor symptoms as well, but it is not considered standard therapy, and cannot be used alone for menopause
*E only (unopposed estrogen) is used for pt with no intact uterus
What is an exception in which Estrogen can be given alone for pt with intact uterus?
Local vaginal estrogen (no/little systemic absorption), for localized urogenital atrophy symptoms only
What are the different Estrogen dosage form types?
Discuss their advantages and disadvantages
- Systemic oral tablets
+ve: inexpensive
-ve: high dose required, hence more side effects
-ve: missed doses can cause irregular bleeding
- Systemic topicals (patches, gels)
+ve: lower systemic dose required compared to oral tablets
+ve: convenient
+ve: continuous estrogen release
-ve: expensive
-ve: skin irritation (rotate application sites)
-ve: gel has more variability in absorption
- Local vaginal (pessary, creams)
+ve: lowest estrogen dose, no concomitant P required
+ve: continuous estrogen release
-ve: inconvenient/uncomfortable
-ve: vaginal discharge
-ve: ONLY used for localized urogenital atrophy
What is the frequency of application of the patches, gels, pessary, and creams
Patch - replace twice a week (lower back, abdomen, thighs, buttocks)
Gel - use ruler to measure and apply dose daily over arms or thighs
Pessary - insert twice a week, just before bedtime to minimize movement
Cream - apply twice a week
How are Estrogen only tablets taken?
Continuous, no placebo
Take same time everyday, once finished with a pack, start new pack immediately
*Recall: pt on this have no uterus hence no bleeding alr
What are the two ways to take Estrogen + Progestin HRT for menopause?
- Continuous-cyclic
- P added on either 1st or 15th of the month, for 10-14 days (half the cycle)
- WIthdrawal bleeding occurs when P is taken off
- Helps to regulate menses and allow predictable bleeding
- Continuous-combined
- E + P combi pills daily
- No withdrawal bleeding, but chance of breakthrough bleeding initially
- Amenorrhea likely to occur after several months
How long must patient be on HRT before improvement of menopausal symptoms is seen?
2-3 months
*Similar to COC, persevere for 2-3 months for adverse effects to go away
What should be assessed upon initiation of HRT?
- Annual mammography (check for breast cancer)
- Endometrial surveillance
- If on unopposed estrogen, should not have any bleeding
- If on continuous-cyclic, should only bleed when off P
- If on continuous-combined, initially breakthrough bleeding only
In what cases should medical attention be seeked when on continuous-combined HRT?
prolonged, heavier than normal, frequent bleeding that persists >10 months after treatment started
What are the chances of symptoms returning after discontinuation of HRT?
50%
What other pharmacological can be used for vasomotor symptoms apart from HRT?
- Antidepressants
- Serotonin and norepinephrine reuptake inhibitors (SNRIs) - Venlafaxine
- Selective serotonin reuptake inhibitors (SSRIs) - Paroxetine
- Gabapentin
- For night sweats, sleep disturbances
What is another pharmacological drug that is a synthetic steroid that can be considered?
Tibolone
- Synthetic steroid with estrogenic, progestogenic, and androgenic effects
- Improves mood, libido, menopause symptoms, vaginal atrophy, also protects against bone loss
- Similar SE/CI: risk of stroke, breast cancer recurrence, endometrial cancer
- **ONLY indicated in postmenopausal women with 12 months since last natural period
- Expensive
