Disorders of Menstruation Flashcards
What is the first day of the menstrual cycle?`
The first day of menses, all hormone levels are relatively low
How many days of the cycle is actual bleeding occuring?
between 3-7, anything >7 is irregular
What hormone does the hypothalamus release?
GnRH
What hormones does the anterior pituitary release?
LH and FSH
What happens ~day 13?
Estradiol levels have reached a peak which stops the anterior pituitary from releasing FSH and start releasing LH which causes ovulation
What does the corpus luteum do?
Secretes progesterone to stabilize the growth of the uterine lining and gets it ready for implantation
What happens around day 21 if pregnancy has not occurred?
Corpus luteum starts dying and secreting lower amounts of progesterone
When progesterone levels start dropping what happens?
menses
**results from the corpus luteum dying which only takes 14 days; this is why the luteal phase is the same for everyone
When is basal body temperature the highest?
ovulation
When does breast tenderness usually happen?
the end of the luteal phase
What is the phase that ranges the most in women?
follicular phase ranges from days to weeks thus determining the length of the cycle
What is dysmenorrhea?
Painful menstruation
What is the difference between acute and chronic pain?
Acute lasts <3 months
Chronic lasts >3 months
What are some causes of cyclic pelvic pain? (3)
- dysmenorrhea
- endometriosis
- mittelschmerz
What is the difference between primary and secondary dysmenorrhea?
Primary: starts 6-12 months after menarche, only happens during ovulatory cycles and is not associated with pelvic pathologies
Secondary: starts 2 or more years after menarche, happens at times other than menarche and typically associated with pelvic pathology
Explain the pathophysiology of dysmenorrhea
After ovulation, progesterone is being released from the corpus luteum which increases arachidonic acid levels
When there is no pregnancy, the corpus luteum dies and arachidonic acid is metabolized into prostaglandins and leukotrienes.
Both increase myometrial contractions, alter blood flow by vasoconstriction and cause uterine ischemia which = pain.
Prostaglandins can also sensitize afferent nerves and cause pain.
What is the relationship between progesterone and prostaglandins?
inversely related
What does nitric oxide do?
Decreases myometrial contractions
What are the risk factors for dysmenorrhea?
- young age
- nulliparity
- early menarche
- smoking
- stress
- positive family history
- heavy flow or long cylce
What patient history information is important to collect for a patient presenting with dysmenorrhea?
- medical and gynecologic
- medication history
- medication allergies or sensitivities
- social history
What are the red flags warranting referral of a patient presenting with dysmenorrhea?
- fever, chills, sign of systemic infection
- IUD inserted in last 6 months
- pain occurs outside first 3 days of menses or persists for 5 days
- sudden onset of pain with bleeding
- unilateral abdominal or pelvic pain
- patient reports palpable lump
- changes in severity or pattern of pain and menstrual fluid
- gynecological symptoms
- new onset of pain in patient with previously pain-free periods
What are the goals of therapy for dysmenorrhea?
1) symptom resolution or improvement
2) minimize disruption of normal activities
3) suppress disease progression
4) identify patients with underlying issues requiring further evaluation
What are the first line treatments for patients presenting with dysmenorrhea?
NSAIDs and hormonal contraceptives
What are the adjunctive non-pharmacological options for the management of dysmenorrhea?
- exercise, low impact
- tobacco cessation
- topical heat therapy
- transcutaneous electrical nerve stimulation
What are the first line non-Rx options for mild primary dysmenorrhea? List the recommended dose and MDD
Ibuprofen
200-400mg every 6-8 hours
1200mg/day MAX
Naproxen
220mg every 8-12 hours
440mg/day MAX
What are the second line non-Rx options for mild primary dysmenorrhea? List the recommended dose and MDD
Acetaminophen
650-1000mg every 4-6 hours
4000mg/day MAX
Aspirin
325-650mg every 4-6 hours
4000mg/day MAX
What is the generic name for pamprin?
Acetaminophen
List the recommended adult dose and MDD for the following Rx NSAIDs:
- Ibuprofen
- Mefanamic acid
- naproxen base
- naproxen sodium
- ketoprofen
- diclofenac
- flurbiprofen
Ibuprofen: 600-800mg Q8H OR loading dose 800mg and 400-800mg Q8H
MDD = 2400mg
Mefanamic acid: loading dose 500mg, then 250mg Q6H
MDD = 1250mg; 1000mg
Naproxen base: loading 500mg then 250mg q6-8h OR 500mg BID
MDD = 1250mg;1000mg
Naproxen sodium: 550mg loading, 275mg q6-8h OR 550mg BID
MDD = 1375mg
Ketoprofen: 25-50mg TID-QID
MDD = 50mg/dose or 300mg/day
Flurbiprofen: 50mg QID
MDD = 200mg
What are the progestin only medications for the management of dsymenorrhea?
Levonorgestrel IUD
Etonogestrel implantable rod - used off label for dysmenorrhea
Depot medroxyprogesterone - option for women who cannot tolerate estrogen and >35 years, or women who smoke
What is the one NHP that has sufficient evidence to say it might be effective in the management of dysmenorrhea?
Thiamine/vitamin B1 100mg/day for 3 months
No contraindications
What are the options for the management of dysmenorrhea if it does not improve within 6 months of NSAIDs and/or COCs?
Refer - medical evaluation necessary to assess for possible causes of secondary dysmenorrhea
If someone is trying to conceive, what can you recommend them for management of dysmenorrhea?
Second line agents (acetaminophen or aspirin)
Avoid using NSAIDs –> may impair implantation of conceptus
What are the product selection guidelines for women who are breastfeeding and experiencing dysmenorrhea?
- acetaminophen and ibuprofen are safe
- avoid use of high dose aspirin (>325mg)
- naproxen is less optimal, medication has a long half life and serious AEs have been reported in neonates
Who should avoid NSAIDs?
- renal impairment (CrCl <30mL/min)
- breastfeeding
- uncontrolled HTN, CV disease, heart failure
- patients taking anticoagulants
What is methocarbamol indicated for?
Backaches and muscle spasms –> make sure if you see the Midol product with this, it isn’t being used for dysmenorrhea
What are some important counselling points when recommending/prescribing NSAIDs for dysmenorrhea?
- optimal dose, frequency
- should be started at symptom or bleeding onset
- pain relief should be 30-60 minutes
- take with full glass of water
- don’t lay down for 20-30 minutes after ingestion
- take with food to prevent GI symptoms
- use lowest effective dose for the shortest possible duration
What is necessary for a pharmacist to do when writing prescriptions for patients?
MANDATORY to notify patient’s primary care provider of the treatment and follow-up plans
What are the steps to take if there is only partial relief after one cycle of NSAIDs versus no benefit after one cycle?
Partial relief: continue for 2 more cycles, try different NSAID or consider COC
No benefit: change NSAID, consider COC
When is full therapeutic benefit seen when NSAIDs are used in the management of dysmenorrhea?
3 months of cyclic treatment using only 2-3 days of the cycle
When does PMS occur?
ONLY in the luteal phase; high fluctuation of progesterone and estradiol
When is the typical onset of PMS?
average age is 26 (late 20s to early 40s)
What are the possible causes of PMS?
Normal shifts in estrogen and progesterone
Dysregulation of neurotransmitter systems; serotonin
What are some of the most common physiological, behavioural and psychological symptoms of PMS?
Physiological: bloating, breast pain/tenderness/swelling, headache
Behavioural: fatigue, food cravings or overeating
Psychological: anxiety, dysphoria, irritability and mood lability
What is the diagnostic criteria for PMS?
NIMH: 30% increase in intensity of PMS symptoms from days 5-10 compared to 6 days before menses AND documentation of these changes in a daily symptom diary for 2 consecutive cycles at least
UCSD: at least one of the affective and somatic symptoms during 5 days before menses in 3 consecutive cycles AND symptoms relieved from days 4-13 of menstrual cycle
What are the risk factors for PMS?
- age
- tobacco use
- alcohol
- stress
- diet (not enough omega 3s)
- lack of exercise
- vitamin D
- identical twins>fraternal twins
- high BMI
- traumatic life events
What are the protective factors for PMS? (4)
- low parity
- COC use
- menstrual cycle characteristics
- socioeconomic or lifestyle variables
What are the red flags to look for when assessing a patient presenting with PMS?
- severe, debilitating symptoms with a strong affective or psychological component
- severe symptoms or interruption of daily functioning
- lack of symptom free period
- symptoms absent in luteal phase
- unresponsive to self treatment
What are the goals of therapy for a patient with PMS? (4)
- ensure that symptoms are not related to another disorder or disease
- relieve symptoms
- minimize functional impairment
- educate patients about PMS
What is the RPh process for diagnosing PMS?
- Occurs in the luteal phase
- Resolves near start of menstruation
- Creates problems or impairment
- Not better explained by another diagnosis
***diagnosis is confirmed through prospective monitoring of a woman’s symptoms from 2 of more menstrual cycles
What are the first line options for management of PMS?
Non-pharmacological options and vitamins
What are the non-pharm measures that can be taken to help with PMS?
Education and support from pharmacist
Stress reduction
- exercise
- sleep hygiene
- COT, relaxation, stress management
Dietary modifications:
- complex carbs
- water
- nutritional supplements
- decrease salt, refined sugar, caffeine, alcohol and smoking
What are the first line options for nutritional supplementation? What do they help with, at what doses and what level of evidence supports it? (4)
Calcium + Vitamin D (600mg BID + 400IU)
- effective for mood and physical symptoms
- STRONG EVIDENCE
Magnesium (200-500mg QD)
- may decrease bloating and irritability
- low evidence, may cause diarrhea
Vitamin B6 (50-100mg QD)
- overall PMS symptoms
- low evidence
Vitamin E (400-600 IU)
- may help with breast tenderness
- low evidence
-
What are the second line herbal remedies for the management of PMS? (5)
STRONG EVIDENCE: Vitex agnus-castus (Chasteberry)
- 30-40mg/day; through cycle or through month
- effective for improving PMS symptoms overall
- similar efficacy to fluoxetine
- SE: nausea, HA
NO EVIDENCE:
- evening primrose oil
- St. John’s Wort
- Ginkgo
- Chinese medicine
Why would oral contraceptives be used to treat PMS and what are the concerns associated with them?
Rationale:
- PMS symptoms occur almost exclusively in ovulatory cycles
- efficacious in improving mood and physical symptoms
- only 1 cycle until onset of effect
Concerns:
- cause hormonal fluctuations; efficacy for cognitive symptoms?
- symptoms occur in the hormone free interval
How are SSRIs part of the treatment of PMS and PMDD?
Efficacious in reducing mood and physical symptoms
Onset of effect within 1 month; most major depressive disorders take 3 months
Is there a clinical difference between dosing SSRIs continuously and only during the luteal phase?
NO
