Premenstrual Syndrome Flashcards
Define premenstrual sydrome
A cyclic recurrence of physical and/or behavioural symptoms that occurs during the luteal phase of the menstrual cycle
(after ovulation and before the onset of menses)
(affects 90% of people who menstruate at some point)
Define PMDD
Premenstrual dysphoric disorder – more severe, disruptive of daily life, ++ mood
(affects 3-8% of people who menstruate)
Define premenstrual exacerbation
Worsening of other disorders during the premenstrual phase (thyroid as example)
When does PMS occur? When does it resolve?
Commonly occurs in the 20’s – Resolves upon menopause
What are the two categories of symptoms of PMS? List the examples?
What are the two phases of the menstrual cycle?
Follicular and Luteal phase
The follicular phase is from the start of menstruation to the moment of ovulation.
The luteal phase is from the moment of ovulation to the start of menstruation (the final 14 days of the cycle)
How long is the luteal phase?
Always 14 days long – 14 days from the start of menstruation
Describe the menstrual cycle
- Hypothalamus release Gonadotropin releasing hormone which causes anterior pituitary to release FSH and LH
- Days 1-4: Increase FSH. FSH stimulates 15-20 primordial follicles in the ovary to start dveloping. As they develop, granulosa cells surrounding them secrete estrogen.
Days 5-7 - One follicle dominant
- Estrogen causes negative feedback onto the anterior pituatary and hypothalamus. As estrogen rises, LH and FSH release are supressed. Stops menstrual flow
Stimulates thickening of endometrial lining
↑ production of thin, watery cervical mucus - Prior to ovulation, estrogen levels drop as follicle is getting to release the ovum. There is a spike in LH that causes the follicles to reach the surface of the ovary and release the ovum. Consistently high estrogen levels stimulate the pituitary to release a mid-cycle surge of LH.
- Luteal Phase. Follicle that released ovum collapses and becomes corpus luteum. The corpus luteum secretes high levels of progesterone and little estrogen and androgens. Progesterone maintains negative feeddback to stop LH and FSH production.
- If ovum fertilized occurs, fetus secretes HCG (human chorionic gonadotrophin) to keep corteus luteum alive.
- If not fertilized, corpeus luteum degenerates and stops producing estrogen and progesterone. This drop removes negative feedback to hypothalamus and pituatary and levels of FSH levels rise again and cycle is restarted (release GnrH). Also, triggers endometrium to break down and mentsrutaion occurs.
Describe the main role of FSH and LH?
FSH – Stimulates the development of follicles
LH – Causes ovulation
What is estrogen? Describe its role?
Sex steroid hormone that acts on estrogen receptors to promote female secondary sexual charcteristics
Develop the breast tissue, vulva, vagina and uterus around puberty
Development of endometrium
Cause mucous in cervix to thin so sperm can penetrate it around the time of ovulation
What is progesterone? What happens if pregnancy occurs?
Steroid sex hormone
- Produced by corpus luteum after ovulation
If preganancy occurs, the placenta takes over production of progesterone around 5-10 weeks of pregnancy
Describe the role of progesterone
Act on same tissues as previously acted on by estrogen:
i) Thickening and maintain endometrium
ii) Thicken cervical mucous
iii) Cause slight increase in body temp
When does menstruation occur? What is menstruation?
Starts on Day 1 of cycle
- Superficial and middle layers of endometrium seperate from basal layer of endometrium
- Tissue broken down in uterus and released through cervix and vagina
- FLuid containing blood released from vagina and lasts 1 to 8 days
Describe the main role of GnRH in the menstrual cycle
Stimulates pituitary to release FSH and LH
Describe the main role of FSH in the menstrual cycle?
Stimulates maturation of follicles in ovaries
Describe the main role of estrogen in the menstrual cycle?
Stimulates thickening of the endometrium (uterine lining)
Suppresses FSH (negative feedback)
Signals LH
Describe the main role of LH in the menstrual cycle?
Triggers ovulation
What is the main role of progesterone in the menstrual cycle?
Produced by the corpus luteum (mass of cells resulting from the ruptured follicle when the ovum is released)
Makes the endometrium favourable for implantation
Signals the hypothalamus and pituitary to stop FSH and LH production (negative feedback)
How long is the average menstrual cycle?
Average cycle is 28 days (range 21-40 days)
What is day 1 of the menstrual cycle?
Day 1 of cycle = first day of period (menses)
Describe the hormone changes throughout the menstrual cycle?
When does ovulation occur in the menstrual cycle?
28-32 hours after LH surge
Describe the MOA of hormonal contraceptives?
Estrogen and progestin provide negative feedback which inhibits ovulation
Estrogen:
Suppresses release of FSH
Progestin:
Suppresses release of LH and FSH
Thickens cervical mucus (impedes sperm transport
Changes endometrial lining (not hospitable to implantation)
Describe the different types of oral combined contraception dosing?
Cyclic
Extended Dosing
Continous Dosing
Describe cyclic dosing of oral combined contraceptives
21 days of active drug + 7 placebo days (hormone free interval; HFI)
Packs may or may not contain 7 placebo tablets
24 days of active drug + 4 days HFI
24 days of active drug + 2 days EE + 2 days HFI
What are the formulations of cyclic dosing regimens?
Monophasic – fixed levels of EE and progestin
Biphasic – fixed EE levels; ↑ progestin in 2nd phase
Triphasic – fixed or variable EE levels; ↑ progestin in all 3 phases
Different colours of pills for different strengths
Why were multiphasic combined oral contraceptives formulated?
Multiphasic products
–> Attempt to imitate the normal menstrual cycle – higher proportion of progestin to EE in second half of cycle
What is the difference in the formulations of cyclic dosing in regards to tolerability?
No difference in efficacy, bleeding patterns, or adverse effects
What is extended dosing of combined oral contraceptives?
> 1 “cycle” of active pills then HFI
84 days of active drug + 7 days EE (low does ethinyl estradoiol) (10mcg) or HFI
What is continous dosing? What formulation is preferred continous dosing?
Uninterrupted, no HFI
Can use any product (<50mcg EE) for continuous dosing (oral, transdermal, vaginal)
Even multiphasic products (according to SOGC)
No products in Canada over 35 mcg
Better if monophasic –> Constant levels of the same dose of hormones, less s/e due to less changing hormones
What is the difference between cyclic, extended, and continuous dosing?
No difference in efficacy or short-term adverse effects between cyclic and extended/continuous dosing.
Less risk of ovulation occurring (most missed doses are the beginning of the pack on time)
Risk of pregnancy is the highest –> Hormone has been gone for more than 7 days so brain starts process for FSH
When does PMS occur within the menstrual cycle?
Luteal Phase - Higher progesterone levels in this phase
In regards to the menstrual cycle, what should be noted regarding the pattern of PMS? Examples?
Has to occur in a cyclic pattern
Examples:
Symptoms at ovulation and gradually worsen
Symptoms begin during 2nd week of luteal phase (right before menses)
Brief episode of symptoms at ovulation, some symptom-free days, then recurrence in late luteal phase
Symptoms at ovulation, worsen during luteal phase, stop only once menses over
What are some of the pathological theories for PMS?
Hormonal Fluctuations
Dysregulation of neurotransmitter systems
Nutritional (calcium) deficiencies
Describe the hormonal theory for the pathophys of PMS
Oversensitivity to circulating progestins (highest during luteal phase)
Describe the dysregulation of neurotransmitter systems theory for the pathophys of PMS
HPO-axis, involvement of serotonin (some evidence of low 5HT levels), others?
Describe the nutritional deficiency theory of the pathophys of PMS?
Related to parathyroid hormone secretion (which would be high if low serum calcium)
Others explored but not substantiated: A, B6, E
What are some of the risk factors for PMS? Are the risk factors the same as dysmenorrhea?
High body mass index: BMI ≥ 30 had 3x risk for PMS than <30
History of domestic violence, physical or emotional trauma, and substance use
Twice as prevalent in identical twins than with fraternal twins (genetic component?)
OPPOSITE TO DYSMENORRHEA
Are the PMS risk factors the same as dysmenorhhea?
PMS risk factors are opposite than dysmenorhhea
Describe the presentation of Sx in PMS
Present during luteal phase
Reach peak shortly before the beginning of menstruation and subside at the onset of menses
Severe enough to interfere with daily functioning and interpersonal relationships
Absent during follicular phase
Describe the diagnosis of PMS
5 or more symptoms that change in severity throughout cycle – must be cyclic – for at least 2 cycles
PRISM – Prospective Record of the Impact and Severity of Menstruation
Number of symptoms for diagnosis may vary (number 5 – CPS)
AND the exclusion of other disorders
Describe the diagnostic criteria of PMDD?
5+ symptoms with at least 1 severe mood symptom for at least 2 cycles – resulting in functional impairment (more debilitating on regular life)
AND the exclusion of other disorders
What type of diagnosis is PMS?
Diagnosis of exclusion – Rule out other conditions
Describe PRISM in monitoring of PMS
Physical or electronic version is effective
If PMS, will see a pattern in 2nd half of cycle
What should be ruled out for a diagnosis of PMS? When do we rule these out?
Rule these out while individual is charting their cycle
Anemia
Diabetes
Thyroid disorder
Chronic fatigue syndrome
Endometriosis
Polycystic ovaries
Adverse effects from OCPs
Perimenopause
Fibrocystic breast changes
Various psychiatric disorders
Describe the differences between PMS and dysmenorhhea in a chart?
What are some of the goals of therapy for the treatment of PMS?
Relieve Sx
Minimize functional impairment
What are some of the lifestyle modifications for PMS?
Reflexology, massage, acupuncture, light therapy, aromatherapy, CBT (low efficacy; stress reduction here)
Appropriate sleep hygiene
Moderate exercise can help breast tenderness, fluid retention, stress, and depression (Moderate aerobic showed some benefit)
What are some dietary modifications that can be utilized in PMS?
↓ methylxanthine-containing foods and caffeine may improve breast symptoms
Tea, coffee, cocoa, chocolate
↑ complex carb intake may lessen appetite changes and cognitive symptoms
Beans, peas, whole grains, vegetables
↓ salt intake can help fluid retention, weight gain, bloating, breast swelling and tenderness (not studied, just recommended)
Describe some of the pharmacologic therapy for PMS
Describe the role, dose and trial/expectations of calcium carbonate in PMS
Negative affect, fluid retention, food cravings, pain
1200 mg (elemental) daily
Expectations – plan for a 3-month trial
What is the main adverse effect of calcium carbonate?
Adverse effects - constipation
What is a counselling tip for calcium usage in PMS?
separate from other meds, Vit D to aid in absorption, ≤ 500mg elemental per dose (DIVIDE DOSE)
What is another reason, not for PMS, that calcium is beneficial in PMS?
PREVENTS OSTEOPOROSIS
Can any form of calcium be used for PMS?
Calcium Carbonate studied; can use other forms – Same efficacy
What are some examples of SSRI’s that can be used in PMS?
Citalopram, escitalopram, fluoxetine, paroxetine, sertraline
Describe the role of SSRI’s in PMS and PMDD
Cognitive > physical symptoms
PMDD > PMS
Describe the efficacy of the SSRI’s in PMS/PMDD, dosing, and when an effect will be notcied?
Effective at low or high doses
Effectiveness does not equate diagnosis of depression
Effect in 1st cycle
SSRI’s – Effects noticed in first cycle – Should be trialled for multiple
Do SNRI’s have the same level of support for PMS than SSRI’s?
No
Less support for SNRI’s
Describe the dosing of SRRI’s in PMS/PMDD?
Continuous use
OR
limited to luteal phase
OR
@ symptom onset
All regimens are effective
Can be dosed OD or intermittent
Triial and error required for dosing schedule
Dose may change during parts of cycle if taking daily e.g, increase to 60 mg if taking 40 mg OD
Describe when an individual should see effect from an SSRI regrading PMS? Is this the same as depression? Why or why not?
Effect should be noted in the first cycle for PMS
It does not take 6-8 weeks to see effect like depression
SSRIs can be effective for PMS within days and usually within 4 weeks
Cochrane authors guess it may be due to:
the cyclical nature of PMS, and
may reflect SSRI action at a different receptor site than those involved in affective disorders
How should an individual with PMS be initiated on an SSRI? What should be monitored/managed?
Transient adverse effects exist and need to be managed
Best practice – use low doses only when needed, consider longer therapy for those with transient effects
What is classified as an adequate trial of an SRRI for PMS?
Adequate trial – 2 cycles; increase dose if partial response; switch SSRI if no response
Describe some side effects of SRRI’s? Are they long lasting?
Headache, nervousness, insomnia, drowsiness, fatigue, GI complaints), more $$ than calcium, drug interactions, serotonin syndrome, sexual dysfunction (if continuous use)
Sx often will resolve within a few weeks
What dose of an SSRI should be initiated for a patient with PMS? What is expected upon discontinuation of a SSRI for PMS?
Start with small doses to minimize transient adverse effects
Symptom relapse upon discontinuation is associated with severity of symptoms
Consider a taper upon discontinuation if using higher doses to minimize withdrawal
Describe the available evidence for SSRI usage in PMS?
COCHRANE REVIEW
31 RCTs that compared SSRI to placebo in total of 4372 women clinically diagnosed with PMS
Findings: SSRIs were effective for reducing symptoms of PMS
Adverse effects more likely in SSRI vs. placebo, most commonly nausea (NNH=7), low energy (NNH=9), somnolence (NNH=13), fatigue (NNH=14), decreased libido (NNH=14), and sweating (NNH=14)
All dose-related
Describe the role of NSAID’s in PMS? Options?
Headache, breast pain, muscle aches
Naproxen or ibuprofen (OTC)
If headache only, could also consider acetaminophen
How should NSAIDs be used in PMS?
Start at onset of pain, use short-term, lowest effective dose (same dosage range as analgesia)
Stop if pregnancy is suspected
What is a benefit of NSAID therapy in PMS?
Could help with differential diagnosis of dysmenorrhea
Describe the role of Pyridoxine (B6) in PMS? Theory for effectiveness?
Excitatory symptoms (anxiety, irritability, panic attacks)
Theory: ↓ B6 –> ↑ prolactin –> edema + psychological symptoms
B6 is co-factor in synthesis of tryptophan and tyrosine → serotonin and dopamine, certain prostaglandins
Balances the inhibitory : excitatory amine ratio
Describe the effectiveness of Pyridoxine (B6) in PMS?
Thought it may help with mood symptoms through production of tryptophan and serotonin
Can be worth a try at low doses
Higher doses –> peripheral neuropathy
Describe the dose of Pyridoxine (B6) in PMS? What is the main concern with pyridoxine and when does it occur?
50 - 100mg po daily
> 200mg = peripheral neuropathy reported
Describe the role of oral contraceptives in PMS?
Inhibit ovulation, but PMS symptoms not connected to ovulation like dysmenorrhea is
May help physical and cognitive symptoms – monophasic preferred
Describe the efficacy of oral contraceptives in PMS?
Most widely prescribed, despite mixed evidence
What type of formulation of oral contraceptives is used for PMS? Why?
Monophasic is preferred - Want to reduce the fluctuations in hormone levels
What type of oral contraceptives should be used in PMS?
Combined oral hormonal contraceptives
Progestin Only contraceptives should not be used
–> progestin can trigger symptoms of PMS (NO PROGESTIN ONLY IN PMS)
Describe the effficacy of COC’s in PMS? What are the respective doses and the risks?
COCs containing ethinyl estradiol 20 or 30 mcg plus drospirenone 3 mg may lessen symptom severity and improve function in patients with severe PMDD symptoms in the short term (unknown effectiveness beyond 3 cycles)
Drospirenone-containing COCs have not demonstrated efficacy in those with less severe PMS symptoms.
In Canada, COCs containing drosperinone are not indicated for PMS or PMDD.
YAZ – approved by FDA for PMS and those who desire COHC
There is a small risk of venous thromboembolic events with the use of any combined oral contraceptive.This risk is slightly higher with those that contain cyproterone or drospirenone
What type of dosing should be used for PMS in regards to OCHC?
Continuous use? Not well studied for PMS
Likely go with standard dosing
What is included in COHC? benefit? What is the risk associated?
Estrogen + drosperinone = anti-mineralocorticoid progestin (21/7 or 24/4)
Fluid retention? Modest at best
VTE? Slightly higher incidence in first few months (low-quality observational evidence) – Hx, fam hx
Overall, describe the evidence for the use of COHC in PMS and PMDD?
Option for those who suffer from severe PMDD and want contraception
Has not shown efficacy in women with less severe PMS
What is drosperinone similar to regarding its mechanism of action?
drosperinone = anti-mineralocorticoid
Spironolactone like effect
What are some of the other pharmacological treatments for PMSS? Concerns/Efficacy?
Pamabrom or caffeine (diuretics) or pyrilamine (antihistamine) – benefit mild at best (MIDOL)
Other antidepressants – all less support than SSRIs
Benzodiazepines – PRN only, concern for dependence/tolerance
Spironolactone – fluid retention only; watch K+
GnRH analogues or danazol – severe, unresponsive cases of PMDD only
Results in pseudomenopausal state and side effects
Overall More Side Effects
What are some of the natural health products that can be used in PMS? Efficacy? What is the main concern with natural health products?
Chasteberry – potentially similar to fluoxetine; varied doses makes a recommendation difficult
Magnesium – maybe for fluid retention; causes diarrhea
Evening Primrose Oil – cyclical mastalgia only; no better than placebo
St. John’s Wort – considered insufficient evidence for PMS
3 trials showed effect for crying, depression, confusion; 1 trial no difference from placebo
If also on OCP, must warn about effectiveness via CYP 3A4 induction
Vitamin E
Ginkgo
Remember – product quality concerns –> None are strictly regulated by Health Canada
Summarize the treatment practices for PMS?
Describe the expectations, monitoring, administration, side effects, when to see MD, and med interactions/cautions?
What is an essential counselling point for an individual who is starting a medication for PMS?
Continue charting PMS symptoms in he menstrual cycle to evaluate efficacy
