womens health Flashcards
menstrual cycle
LH and FSH peak at ovulation estradiol drops off at ovulation progesterone rises after ovulation follicular phase: menstruation - ovulation luteal phase - ovulation - menstruation
changes to ADME during menstrual cycle
A: no change
D: no change
M: variable effects
renal elimination: Dec. GFR early follicular phase, Inc. GFR in luteal phase
changes to ADME during pregnancy
A: Dec. motility/ intestinal blood flow, Inc. gastric pH
D: Inc. blood volume, Dec. albumin
M: Dec. 1A2, 2C19, Inc. 2A6, 2C9, 2D6 (3rd tri), 3A4
renal elimination: Inc. renal blood flow and GFR
changes to ADME to elderly women
A: Inc. gastric pH, Dec. gastric emptying, Dec. GI blood flow
D: Dec. Vd for hydrophilic, Inc. Vd for lipophilic, Dec. protein binding
M: Variable influences on CYP
renal elimination: decreased creatinine clearance
well woman visit
vital signs: BP, weight/BMI
breast exam: visual inspection, manual exam
pelvic exam: external inspection, speculum exam, pap smear
pap smear recommendations
Every 3 years starting at age 21
Co-test with human papillomavirus (HPV) every 5 years after age 30
Not needed if under 21 years old, 65 years old if low risk, After hysterectomy with cervix removal if no history of pre-cancer/cancer
screening and counseling
Cervical cancer Substance abuse Domestic violence Hyperlipidemia Hypertension Diabetes Sexually transmitted infections (STIs) Thyroid function Vaccine history Osteoporosis Colorectal cancer Breast cancer Obesity Eating disorders Pelvic organ prolapse Incontinence Sexual dysfunction Depression Contraception
contraception overview
62 million women of reproductive age in US
43 million are sexually active and do not want to become pregnant
Average woman must use for around 30 years throughout life
46% of women with an unintended pregnancy did not use contraception
methods of contraception
Abstinence
Non-hormonal
Hormonal
nonhormonal methods of contraception
Behavioral - Coitus interruptus, Lactation amenorrhea method (LAM), Fertility awareness methods (FAM) and natural family planning (NFP)
basal body temp (BBT)
predicts ovulation of regular cycles
reaches low point during ovulation (around 97) then spikes to 98 within 2 days
billings ovulation method
cervical mucous
irregular cycles
calendar/rhythm method
based on past cycles
shortest cycle - 18 = first fertile day
longest cycle - 11 = last fertile day
standard days method
26-32 day cycles
track cycle and difference colored beads tell when pregnancy is most likely
two day method
cervical secretion
secretions either today or yesterday = fertile
FAM and NFP overview
Effectiveness: 3 – 22% failure rate
Advantages: No effect on hormones/cycle, No side effects!, Inexpensive (except for electronic monitor), Acceptable to many cultures/religions
Disadvantages: No STI protection, Difficult if irregular cycles
nonhormonal contracteptives
male condom
-advantages: low cost, HIV/STI protection
-disadvantages: used dependent, slippage/breakage
female condom
-advantages: insert up to 8 hours before, HIV/STI protection
-disadvantages: user dependent
vaginal sponge
-advantages: protect for 24 hours from insertion
-disadvantages: no HIV/STI protection, user dependent
spermidide
-advantages: rapid onset
-disadvantages: no HIV/STI protection, short duration, resupply for repeated intercourse
diaphragm (w. spermicide)
-advantages: insert 6-8 hours before no systemic SEs
-disadvantges: must be properly fitted, no HIV protection, UTI/TSS risk
cervical cap
-advantages: protect for up to 48 hours, no systemic SEs
-disadvantages: must be properly fitted, no HIV protection, UTI/TSS risk
copper IUD
-advantages: long term
-disadvantages: insert/remove by HCP, $$$ up front, no HIV protection, SEs
hormonal contraception
progestin:
-Prevent LH surge - inhibit ovulation
-Thicken cervical mucus - inhibit sperm penetration/transport
-Change motility of fallopian tubes - impair transport of sperm/ova
-Atrophy of endometrium
estrogen:
-Suppress FSH production - prevent selection/emergence of dominant follicle
-Increase sex-hormone binding globulin - increase binding of free androgens
combined oral contraceptives (COC)
Monophasic vs. multiphasic Estrogen component: -Majority contain 20 – 35 mcg ethinyl estradiol (EE) -Some contain up to 50 mcg EE -Some contain mestranol (50 mcg mestranol = 35 mcg EE) Very low dose = 20-25 mcg EE Low dose = 30-35 mcg EE High dose = 50 mcg EE
side effects of too much estrogen
Bloating Breast tenderness Mood changes Headache Nausea Heavy menses Fibroid growth Melasma Vision changes Cyclic weight gain
side effects of not enough estrogen
Breakthrough bleeding early in cycle Light menses Vaginal dryness Spotting No withdrawal bleeding
progestin component effects
Progestational -Prevent ovulation -Lessen bleeding -Desire high selectivity Androgenic -acne -hirsuitism -desire lower activity estrogenic -decrease androgenic side effects
progestin component exampes
estranes - derivateives of norethidrone: Norethindrone, norethindrone acetate, ethynodiol diacetate
gonanes - derivates or norgestrel: norgestrel, lovenorgestrel, desogestrel, norgestimate
drospirenone - analogue of spironolactone
SEs from too much progestin
Acne Hirsutism Change in sex drive Depression Increased appetite Noncyclical weight gain Less energy Cholestatic jaundice Yeast infections Hair loss Swelling in arms/legs
SEs from not enough progestin
Breakthrough bleeding late in cycle
No withdrawal bleeding
Heavy menses
serious SEs from COC
ACHES
A – Abdominal pain - liver problem, gallbladder, clot
C – Chest pain (SOB, coughing) - PE, MI
H – Headache (severe HA, dizziness) - HTN, stroke, migraine
E – Eye problems (double vision, blurry vision) - Stroke, HTN
S – Severe leg pain (calf or thigh) - DVT
COC and antibiotics
Controversial!!
Potential mechanisms: Altered intestinal flora, Increased nausea/vomiting/diarrhea as a side effect of antibiotic, Altered metabolism
Rifampin & rifabutin are known 3A4 inducers
Better safe than sorry - recommend backup plan!!
COC dosing considerations of start date
start date: day 1 - take on first day of period, don’t need back-up method
state date: sunday start - first sunday during or immediately following menstrual cycle, use back-up method for 7 days
start date: quick start - start immediately regardless of paint in menstrual cycle, use back-up method of 7 days
COC other dosing considerations
Continuous use
-Skip placebo pills
-Decreased chance of side effects with monophasic COC
21 day vs. 28 day pack
Switching brands/types
-Generally start new product on same day a new pack of previous COC would have been started
skipped pill in first week?
use back up for 7 days
skipped pill in weeks 2-3?
take when remember, then continue
skipped 2 pills? take one with next dose and leave the other in the pack - use a back up method for 7 day
transdermal hormonal contraceptive
Ortho-Evra
EE 35 mcg/day + norelgestromin 150 mcg/day
One patch per week x 3 weeks then one week patch-free
Sites: upper outer arm, abdomen, buttock or back
Size: 1.75 inches x 1.75 inches
Less effective if over 198 lbs (90 kg)
same starting info as COCs
If switching: apply first patch on day you would start new pack or new ring cycle
Edge lifts up: Press down firmly for 10 seconds; smooth out wrinkles, If does not stick completely, remove and apply replacement patch
Off/partially off:
-less than 1 day: try to reapply but use new patch if does not stick completely; no back up method needed
-over 1 day: apply new patch and restart 4 week cycle; use back up method for 7 days
transvagnial ring hormonal contraceptive
NuvaRing
EE 0.015 mg/day + etonogestrel 0.12 mg/day
Insert and use continuously for 3 weeks; remove for 1 week
Diameter = 54 mm (2.1 inches)
Day 1 vs. Day 2-5 Start vs. Quick Start
-Recommended to be started by day 5 of cycle (not Sunday)
-Backup method needed if day 2-5
Switching: can start at any point
Backup method should NOT be a diaphragm
No “proper” position for ring as long as fully inserted in vagina
What if NuvaRing falls out?
-less than 3 hours: rinse with cool water and reinsert
-over 3 hours & week 1 or 2: reinsert ring and use backup method for 7 days
-over 3 hours & week 3: discard Nuvaring; insert new ring and restart 21 day cycle OR wait up to 7 days and start next ring cycle; use backup method for 7 days following new ring insertion
risks of hormonal contraception
Breast cancer: conflicting evidence Ovarian cancer: decreased risk Uterine cancer: decreased risk Cervical cancer: conflicting evidence Cardiovascular/circulatory system: -Increased risk of VTE -Conflicting evidence for stroke/MI -Increased blood pressure
contraindications with COC
less than 21 days postpartum
Severe decompensated cirrhosis
VTE
Diabetes and vascular disease
Migraine with aura
HTN and BP over 160/100 or vascular disease
Smoking over 15 cigarettes per day and age over 35
Hx of stroke
Major surgery with prolonged immobilization
IHD (current or hx)
Liver tumor (adenoma or malignant)
Peripartum cardiomyopathy
Complicated solid organ transplant
SLE and positive antiphospholipid antibodies
Complicated valvular heart disease
precautions with COC
Hx of breast cancer (over 5 years)
21-30 days postpartum (42 if VTE risk factors)
VTE (lower risk for recurrence)
Superficial venous thrombosis
Diabetes and vascular disease
HTN controlled or 140-159/90-99
Smoking, under 15 cigarettes per day and over 35 years old
Inflammatory bowel disease
Multiple risk factors for ASCVD
Hx of malabsorptive bariatric surgery
Hx of COC related cholestasis
Multiple sclerosis with prolonged immobility
Peripartum cardiomyopathy over 6 months
Antiretroviral, anticonvulsant, rifampin or rifabutin therapy
progestin only contraceptives - oral norethindrone or norgestrel
- “Minipill”
- Taken continuously - no placebo pills or breaks
- Doses must be taken within 3 hours of scheduled time
- If late/missed then use backup method for 48 hours
- Failure rate slightly higher in those over 154 lbs (70 kg)
- Metabolized via CYP450 - interactions (esp. inducers)
- Recommended for breast-feeding women
progestin only contraceptives - injectable medroxyprogesterone acetate
Intramuscular
-Depo-Provera CI (150 mg medroxyprogesterone acetate)
-Gluteal or deltoid muscle
Subcutaneous
-Depo-SubQ Provera 104 (104 mg medroxyprogesterone acetate)
-Anterior thigh or abdomen
Initial injection within 5 days of start of period
Q3 months
Consider limiting use for less than 2 years
-Impact on bone mineral density
-Weight gain
progestin only contraceptives - subdermal
Nexplanon (68 mg etonogestrel)
Rod inserted into inner side of non-dominant upper arm
Up to 3 years
Initial insertion within 5 days of start of period
Other timing = backup method for 7 days
side effects of progestin only contraceptives
Irregular bleeding Irritation at injection/implant site Weight increase Bone loss (IM) Return to fertility prolonged (IM/implant)
precautions and contraindications for progestin only contraceptives
Current breast cancer
Caution in:
-Hx of breast cancer
-Severe decompensated cirrhosis
-Malabsorptive bariatric surgery procedure
-Liver tumors
-SLE
-Ritonavir-boosted protease inhibitor HAART
-In combination with certain anticonvulsants
-In combination with rifampin or rifabutin
intrauterine devices (IUD) overview
Disruption in tubal transport of sperm and ovum & prevention of implantation
Thickening of cervical mucus & alteration of the endometrium
Insert during first 7 days of cycle
non-hormonal: copper, up to 10 years
hormonal:
-mirena - 52 mg levonorgentral, up to 5 years
-skyla - 13.5 mg levonorgestrel, up to 3 years
-liletta - 52 mg levonorgestel, up to 3 years
side effects of IUDs
Infection Perforation of uterus Irregular bleeding Dysmenorrhea/amenorrhea Lower abdominal pain Acne Breast tenderness Headaches Mood changes Nausea
precautions and contraindications of IUDs
Distorted uterine cavity
Current breast cancer (progesterone only – can use copper)
Cervical cancer not yet treated
Endometrial cancer
Current pelvic inflammatory disease (PID)
Within 3 months of septic abortion
Postpartum puerperal sepsis
Current STI (purulent cervicitis, chlamydia, gonorrhea)
Pelvic tuberculosis
Unexplained vaginal bleeding
emergency contraception
Prevention of pregnancy after intercourse
- Prevent/delay ovulation
- Prevent fertilization
- Prevent implantation
four methods of emergency contraception
Levonorgestrel emergency contraceptive pills (ECPs)
Combined ECPs
Ulipristal acetate
Copper IUD
levonorgestrel ECP
Single dose: Plan B One-Step, Next Choice One-Step, 1.5 mg levonorgestrel
Two doses: Next Choice, Plan B (being phased out), 0.75 mg levonorgestrel q 12 h x 2
Use within 72 hours (up to 120 hours?)
Failure rate of 0.4% - 2.7%
Available OTC
combination ECP
No marketed product but 22 COCs declared safe and effective by FDA
At least EE 100 mcg and levonorgestrol 0.50 mg per dose - 2-4 tablets = 1 dose
Norgestrel preferred over norethindrone
1 dose q12 h x 2
First dose within 120 hours
Failure rate of 0.5% - 4.2%
ulipristal acetate
ella Selective progesterone receptor modulator 30 mg tablet x 1 dose - Rx ONLY Within 120 hours Failure rate of 0.9% - 1.8%
copper IUD for emergency contraception
Insert within 5 days
Failure rate of 0.1%
side effects of emergency contraception
Nausea and vomiting Spotting Changes in next menses Headache Breast tenderness Mood changes Abdominal pain
precautions and contraindications of ECPs
contraindications: pregnancy (known or suspected)
precautions: hx of actopic pregnancy, use w CYP3A4 inducers
return of fertility
Combined hormonal contraceptives: 1-2 weeks
Injectable progestin: 10 months
Progestin implant: 30 days
IUD: 30 days
Emergency contraception: immediate
Postpartum: around 21 days; may be extended with breastfeeding
non-contraceptive uses of hormonal products
Regulation of menstrual periods Treatment of -Heavy periods (menorrhagia) -Painful periods (dysmenorrhea) -Endometriosis -PMS and PMDD -Acne, hirsutism and alopecia
COC monophasic doses
very low dose: EE 20 mcg + progestin
low dose: EE 30-35 mcg + progestin
high dose: EE 50 mcg + progestin
biphasic, triphasic, four phasic
biphasic: varying doses of EE or progestin; 2 strengths throughout cycle
triphasic: varying doses of EE or progestin; 3 strengths throughout cycle
four phasic: varying doses of EE and progestin; 4 strengths throughout cycle
“other” product hints
extended cycle COC: monophasic or biphasic, active pill up to 84 days
progestin only COC: no estrogen component, norethindrone 0.35 mg daily
non-oral hormone: EE + progestin = nuvaring or patch; progestin only = IUD, IM/SQ inj or rod
emergency contraception: typically no estrogen, 1-2 doses depending on product
pharmacist “prescribing” of oral contraceptives
legislation in california and oregon
considering legislation in hawaii, missouri, SC, tennessee, washington
california law
Oral hormonal contraceptives Hormonal contraceptive patches Vaginal hormonal rings Hormonal depot injections Training: -1-hr board-approved CE program -Curriculum-based training post-2014
oregon law
Oral hormonal contraceptives
Hormonal contraceptive patches
Training:
-5-hr board-approved CE program
procedure for prescribing contraceptives
- patient completes self-screening tool
- RPh review/clarify responses
- recommend product or refer
- measure/record seated BP if combined hormonal product
- train on administration
- provide appropriate counseling and fact sheet
product selection
Based on CDC’s US Medical Eligibility Criteria (USMEC)
May select any product listed as Category 1 or 2 within scope of the law
If Category 3-4 OR wants product that is not self-administered
-Refer to PCP
-If no PCP, refer to nearby clinic
pharmacist conscience clause
Refusal to fill a prescription on religious or moral grounds
Some states have laws allowing pharmacists to refuse to fill - Arizona, Arkansas, Georgia, Idaho, Mississippi, South Dakota
Some states have laws requiring pharmacists to fill - California, Illinois, New Jersey
HPV
Most common STI in United States
-over 6 million people newly infected each year
-At least 50% of sexually active people infected at some point during lifetime
over 200 serotypes identified
-15 high-risk
-3 most likely high-risk
-12 appear low-risk
Can be spread via vaginal, anal and oral sexual contact
Treatment for warts, not eradication of virus
complications of HPV
Genital warts: types 6 & 11 Cervical cancer: types 16 & 18 Anal cancer: type 16 Vulvar, vaginal and penile cancer: types 16 & 18 Oropharyngeal cancer: type 16
HPV vaccines
cervarix: serotypes 16 and 18, administration at 0, 1 and 6 months, indicated for females 9-25
gardasil: serotypes 6, 11, 16 and 18, administration at 0, 2 and 6 months, indicated for females 9-26 and males 9-26
gardasil 9: serotypes 6, 11, 16, 18, 31, 33, 45, 52, and 58, administration at 0, 2 and 6 months, indicated for females 9-26 and males 9-15 (9-26)
SE of HPV vaccine
Injection site reaction Fever Headache Nausea Muscle/joint pain Syncope Dizziness Guillain-Barre syndrome Complex regional pain syndrome (CRPS) Postural orthostatic tachycardia syndrome (POTS)
Premenstrual Syndrome (PMS) & Premenstrual Dysphoric Disorder (PMDD)
Recurrent moderate psychological and physical symptoms
Occur during luteal phase
Resolve with menstruation
over 200 symptoms
prevalence of PMS and PMDD
70-90% Premenstrual symptoms at some point in their life
20-40% experience premenstrual syndrome
3-8% have premenstrual dysphoric disorder
pathophys of PMS/PMDD
not well understood
reduced levels of: serotonin, GABA and allopregnanolone
fluctuations in: estrogen and progesterone
common sxs of PMS
physical/somatic: breast tenderness, *abdominal bloating, HA, swelling of extremities, body aches, *fatigue
affective/emotional: depression, angry outbursts, irritability, anxiety, confusion, *mood swings
cognitive: difficulty concentrating, sleep disturbances
behavioral: reduced interest in usual activities, appetite changes, social withdrawal
normal premenstrual symptoms
One or more mild emotional or physical symptoms
One to two days before the onset of menses
Do not cause distress or functional impairment
PMS
At least one symptom associated with “economic or social dysfunction”
Five days before the onset of menses
Present in at least three consecutive menstrual cycles
PMDD
Diagnostic and Statistical Manual of Mental Disorders (DSM-5) full category/diagnostic code
At least five symptoms in final week before menses
Improve within a few days of onset of menses
Become minimal or absent in week post-menses
Present in majority of cycles
Confirmed by prospective daily rating during at least 2 symptomatic cycles
PMDD sxs for diagnosis
at least one: Affective lability, Irritability, anger or interpersonal conflicts, Depressed mood, feelings of hopelessness or self-deprecating thoughts, Anxiety, tension or feelings of being keyed up/on edge
at least one: Decreased interest in usual activities, Difficulty in concentration, Lethargy, easily fatigued or lack of energy, Change in appetite, overeating or specific food cravings, Hypersomnia or insomnia, Feeling overwhelmed or out of control, Physical symptoms (breast tenderness/swelling, joint or muscle pain, bloating, weight gain)
**total symptoms greater than or equal to 5
summary of normal v PMS v PMDD
Normal: 1 or more symptoms, mild/no functional impairment, sxs occur 1-2 days before menses
PMS: 1 or more sxs, economic or social impairment, sxs occur 5 days before menses for 3 consecutive cycles
PMDD: 5 or more sxs, cause significant distress/interference w daily life, start 7 days before menses and resolves within a few days for at least 2 cycles
nonpharm treatment for PMDD
Aerobic exercise Relaxation techniques Calcium carbonate 1200 mg/day Vitamin B6 50-100 mg/day Reduced caffeine, refined sugars, and sodium
pharmacologic therapy for PMDD
first line: SSRIs
second/third line: GnRH agonists, alprazolam
potential effectiveness: COC, spironolactone
last line: surgery
SSRIs for PMDD
FDA approved: fluoxetine 20 mg daily, sertraline 50-150 mg daily, paroxetine CR 12.5-25 mg daily
not FDA approved: citalopram 20-30 mg daily, escitalopram 10-20 mg daily
intermittent dosing: Start on day 14 of cycle, Stop 1-2 days after onset of menses, Consider weekly dosing of fluoxetine 90 mg twice during luteal phase
continuous/daily dosing: Mood symptoms outside of luteal phase, Irregular menstrual cycle, Intolerable side effects upon discontinuation, Difficulties with on/off schedule
SSRI considerations
Black Box Warning: Increased risk of suicidal thinking and behavior in children, adolescents and young adults with major depressive disorder and other psychiatric disorders
SEs: Nause, Fatigue, Somnolence, Decreased libido, Sweating, Insomnia, Anxiety, Diarrhea, Headache
alprazolam
2nd-3rd line option
Dose: 0.25mg PO BID-QID during the luteal phase
Does not improve physical/somatic symptoms
Used to augment SSRI therapy
Risk of dependence and tolerance
Side effects: cognitive dysfunction, fatigue, irritability, decreased libido, weight loss/gain, change in appetite, constipation, decreased salivation
gonadotropin-releasing hormone analogs
Leuprolide, goserelin, nafarelin, histrelin
-PMS and PMDD non-FDA approved indications
Reductions in psychoemotional and physical symptoms
Difficult to tolerate
Must use add-back therapy after 6-9 months because of reductions in bone mass