Women's Health Flashcards
First Phase: Follicular phase (proliferative phase)
- endometrium builds up d/t estrogen which leads to production of estradiol
- regulated by FSH which stimulates follicles to develop and mature
- egg released after about 14th day of menstrual cycle
- LH surges and leads to ovulation
- after ovulation, endometrium proliferates
Second Phase: Luteal phase
- progesterone produced by luteum and plays big part in this phase
- temp increases 1/2 to 1 degree farenheit
- ovum travels as a blastocyte via fallopian tube to uterus for implantation
- after implantation, hCG starts to be produced to help maintain the corpus luteum to support the ovum/zygote
Polymenorrhea
21 day cycle
oligomenorrhea
cycle >35 days
amenorrhea
cycle >180 days (6 months)
Menorrhagia
heavy flow
metrorrhagia aka menometrorrhagia
prolonged bleedings with no clear pattern
What are used in replacement therapy, contraception, and/or management of menopause
gonadal hormone made from cholesterol
estradiol
—most potent estrogen; secreted in the ovary by the premenopausal woman
estrone
metabolite of estradiol; 1/3 of the potency of Estradiol; primary estrogen in the postmenopausal woman; generated from conversion of androstenedione in the peripheral and
adipose tissues
estriol
another metabolite of Estradiol; much less potent than Estradiol; principal estrogen produced by the placenta
Conjugated Equine Estrogen
sulfate esters of Estrone + Equilin is a common oral estrogen used as
HRT [Premarin]
Synthetic estrogens—ethinyl estradio
undergoes less liver metabolism than naturally occurring estrogens, so can be safely used at low doses
SERMs
Nonsteroidal compounds that bind to estrogen receptors [have both estrogen and anti-estrogen effects]
-ex: tamoxifene and raloxifene
MOA of estrogens
-activated steroid-receptor complex interacts with nuclear chromatin to initiate
hormone specific RNA synthesis
- Used for postmenopausal hormone therapy, contraception, replacement in the
premenopausal patients who are deficient [hypogonadism, premature menopause,
surgical menopause
Postmenopausal Hormone Therapy
Used in vasomotor instability, vaginal atrophy
If the woman has a uterus, progestogen must be included to reduce the risk of
endometrial cancer
If the woman has had a hysterectomy, unopposed estrogen is used—progestins may have
negative effects on the lipid panel
ADE are less than in those using estrogens for contraception
Estradiol by patch or gel is also effective for postmenopausal symptoms
Risks of HRT—increased risk of CV events and breast cancer
Women with only GU symptoms are best treated with vaginal estrogens
Other uses for postmenopausal hormone therapy
Contraception
- Combination of estrogen and progestogen is used
Primary Hypogonadism - Estrogen that mimics natural cycle + progestogen to stimulate development of secondary sexual characteristics - Must be continued until after growth has been completed
Premature Menopause
- Estrogen + progestogen replacement is
used
Naturally Occurring Estrogens
Absorbed though the GI tract, skin & mucous membranes
Taken orally, estradiol is rapidly metabolized by the liver; micronized
estradiol is available and has better bioavailability
Synthetic Estrogen Analogs
Ethinyl estradiol, mestranol & estradiol valerate are well absorbed after oral
ingestion
These are fat soluble, they are stored in adipose tissues, from there they are slowly released
Synthetic estrogen analogs have prolonged action & are more potent than natural estrogens
Metabolism of estrogens
Estrogens are transported to the blood bound to albumin or SHBG;
bioavailability of oral estrogen is low [because of 1st pass metabolism]; to
reduce 1st pass effects—give the drug transdermally, intravaginally or by
injection
They are then hydroxylated in the liver to derivatives that are then
glucuronidated or sulfated
The parent drugs and the metabolites are excreted into the bile and are then
reabsorbed through the enterohepatic circulation; inactive products are
excreted in the urine
Adverse effects of estrogen
Nausea Breast tenderness Elevation of BP Elevation of triglycerides Peripheral edema Increased risk of VTE and MI Increased risk of breast and endometrial cancer [endometrial cancer risk reduced by concomitant use of a progestin]
Selective Estrogen Receptor Modulators
Estrogen related compounds that display selective agonism or antagonism for estrogen
receptors—depending on the target tissue
SERM examples
Tamoxifen Toremifene [Fareston] not prescribed in US Raloxifene [Evista] Clomiphene [Clomid] Ospemifene [Osphena]
How does tamoxifen, toremifene, and raloxifene work?
By compete with estrogen for binding to the estrogen receptor in the breast tissue
Raloxifene (Evista) works by…
Raloxifene also acts as an estrogen agonist in the bone, leading to decreased bone resorption, increased bone density and decreased vertebral fractures. Unlike
Tamoxifen and estrogen,
Raloxifene does not have appreciable estrogen receptor agonist activity in the endometrium [so no increased risk of endometrial cancer]
Raloxifene also lowers total and LDL cholesterols
Clomiphene works by…
Clomiphene acts as a partial estrogen agonist and interferes with the negative feedback of estrogens on the hypothalamus
These effects increase secretion of gonadotrophin releasing hormone and gonadotropins—stimulating ovulation
What is tamoxifen used for?
in—metastatic breast cancer; add on therapy after mastectomy or XRT for breast cancer; prevention of breast cancer in those at high risk
What is Raloxifene used for?
prevention of breast cancer in those at high risk; prevention and treatment
What is Clomiphene used for?
used for infertility from
anovulatory cycles
What is Ospemifene used for?
—treatment of dyspareunia from
menopause
Pharmacokinetics of SERMs
SERMs rapidly absorbed after PO administration
Tamoxifen—metabolized by CYP450 isoenzymes
Raloxifene—rapidly converted to glucuronide conjugates through 1st pass metabolism; undergoes enterohepatic cycling—main route is excretion through the bile into the feces
ADE of tamoxifen and toremifene
—hot flashes; nausea; endometrial hyperplasia and
malignancies have been reported with Tamoxifen
ADE of raloxifene
hot flashes and leg cramps; increased risk of DVT, PE and retinal vein
thrombosis; avoid use of Questran while taking Raloxifene
ADE of clomiphene
headache, nausea, vasomotor flushes, visual disturbances, ovarian
enlargement, increased risk of multiple births [these effects are dose related]
what is Progesterone
natural progestogen; produced in response to LH in women & by the testes in men; also produced by adrenal cortex in
both sexes
MOA of Progesterone
In women—progesterone promotes development of secretory endometrium that
accommodates implantation of newly forming embryo
High levels released during the luteal phase inhibit the production of gonadotropin and
prevent ovulation—if conception occurs, progesterone continues to be produced to
maintain the endometrium & reduce the uterine contractions
If conception does not occur, release of progesterone from corpus luteum stops—this decline causes menstruation to take place
Therapeutic uses of progesterone
Contraception
Treatment of hormone deficiency
Control of DUB (dysfunctional uterine bleeding), dysmenorrhea, endometriosis management and infertility
For contraception—they are combined with estrogens
Synthetic progestogens—progestin used in contraception are more stable to first pass
metabolism
- Desogestrel, Dienogest, Drospirenone, Levonorgestrel, Norethindrone, Norethindrone acetate,
Norgestimate, Norgestrel
- Medroxyprogesterone acetate injection [this agent is used orally as part of HRT]
Pharmacokinetics of progesterone
Micronized progesterone is rapidly absorbed after oral ingestion
Metabolized by liver; glucuronidated metabolite is excreted by the kidney
Oral medroxyprogesterone acetate has a ½ life of 30 days; when given IM or SC the ½ life is about 40-50 days and gives
contraceptive activity for approximately 90 days; other progestins have ½ lives of 1-
3 days allowing for once a day dosing
ADEs of progesterone
ADEs
- Headache
- Depression
- Weight gain
- Changes in libido
Progestins that are derived from 19- nortestosterone possess some androgenic
activity because of their similarity to
testosterone—can cause acne and hirsutism
Those that are less androgenic—norgestimate
and drospirenone, are preferred in women
with acne [can raise K+]
Antiprogestins
Progesterone antagonist with partial agonist activity
Use of this drug early in pregnancy usually in abortion due to
interference with the progesterone
Often combined with the prostaglandin analog Misoprostol [PO
or intravaginally] to induce contractions—uterine bleeding and
the possibility of incomplete abortion
Example of antiprogestin
Mifepristone [RU-486]
✹Progesterone antagonist with partial agonist activity
✹Use of this drug early in pregnancy usually in abortion due to
interference with the progesterone
✹Often combined with the prostaglandin analog Misoprostol [PO or intravaginally] to induce contractions—uterine bleeding and
the possibility of incomplete abortion
Major classes of contraceptives (COCs)
Combination on an estrogen & a progestin
Triphasic COC attempt to mimic the natural female cycle—most contain a constant dose
of estrogen with increasing doses of progestin given over 3 successive 7 day periods
Active pills are taken for 21-24 days, followed by 4-7 days of placebo, for a total regimen of 28 days—withdrawal bleeding occurs during the hormone free period
Extended cycle contraception [84 pills followed by 7 days of placebo] results in less
frequent withdrawal bleeding
Most common estrogen COC
ethinyl estradiol
Most common progestins im COCs
—norethindrone, norethindrone acetate, levonorgestrel, desogestrel, norgestimate and drosperidone
Contraceptive patches
Ethinyl Estradiol and Norelgestromin Patch is applied weekly for 3 weeks to abdomen, torso or buttocks 4th week no patch is worn Efficacy comparable to COCs in women weighing <90 kg Total estrogen exposure greater than with COCs
Contraceptive ring
Vaginal ring of Ethinyl Estradiol and
Etonogestrel
Ring left in place for 3 weeks, then left out
for r1 week
Efficacy, contraindications & ADEs similar
to COCs
Progestin Pills
Norethindrone—called “Mini Pill” Taken daily Less effective than COCs; they may produce irregular menstrual cycles Can be used while breast feeding, can be used in those intolerant to estrogen, those that smoke or those with contraindications to estrogens
Progestin Injections
Medroxyprogesterone acetate given IM or SC every 90 days ADE Weight gain Amenorrhea Bone loss/osteoporosis Return to fertility may be delayed for several months after discontinuation Drug should not be used for >2 years unless patient is unable to use other methods
LARCs-progestin Based Implants
Subdermal Etonogestrel Ensures contraception for 3 years Effect totally reversible when surgically removed ADEs—irregular menses; headaches Has not been studied in women >130% of IBW
LARCs-progestin based
Levonorgestrel releasing IUD system Lasts for 3-5 years Suitable for those who have contraindications to estrogens; avoid in patients with PID or hx of ectopic pregnancy
Emergency Contraception
Reduces chance of pregnancy after an episode of unprotected or ineffectively protected intercourse Reduces chance of pregnancy to 0.2-3% High doses of Levonorgestrel or high doses of Ethinyl Estradiol + Levonorgestrel Should be taken ASAP after the intercourse—preferably within 72°
Alternative for emergency contraceptive
Progesterone agonist/antagonist—
Ulipristal [Ella] can be used as EC
within 5 days of unprotected
intercourse
MOA of contraceptives
Estrogens provide a negative feedback on the release of LH and
FSH by he pituitary—preventing ovulation
Progestins thicken cervical mucous, interfering with the transport of
sperm
Withdrawal of the progestin stimulated menstrual bleeding
ADEs of estrogen contraceptives
Breast fullness Fluid retention Headache Nausea Elevated BP Thromboembolism Thrombophlebitis MI Stroke
ADEs of progestin contraceptives
Depression
Changes in libido
Hirsutism
Acne
COCs are contraindicated for:
contraindicated in presence of cerebrovascular and thromboembolic disease, estrogen dependent cancers,
liver disease and pregnancy
COCs increase risk for what kind of caner
cervical
COCs decrease risk for which cancers
endometrial and ovarian
COCs should not be used in
> 36 years and are smokers
Androgens
Steroids that have anabolic and/or masculinizing effects in both men and women
Testosterone—synthesized by Leydig cells in the testes & in smaller amounts by thecal cells in the ovaries and adrenal gland [in both sexes]
Other androgens secreted by the testes—5 alpha dihydrotestosterone [DHT]; androstenedione dehydroepiandrosterone [DHEA]
Testosterone secretion by Leydig cells is controlled by gonadotrophin-releasing hormone from
the hypothalamus, which stimulates the anterior pituitary to secrete LH and FSH
Testosterone or its active metabolite [DHT] inhibits production of these specific trophic
hormones
Androgens are needed for—normal male maturation, sperm production, increased production
of muscle proteins, Hbg. and decreased bone resorption
MOA for androgens
Testosterone must be reduced to its active derivatives, such as DHT
The derivatives then diffuse into the prostate, seminal vesicles, epididymis and skin
Testosterone is converted by 5 alpha reductase to DHT
Therapeutic uses of androgens
Used for males with primary hypogonadism or secondary hypogonadism [due to failure of the hypothalamus or pituitary]
Anabolic steroids can be used to treat chronic wasting associated with HIV or cancer
Unapproved uses—increased lean body mass, muscle strength and endurance in athletes; DHEA has been touted as an antiaging hormone
Danazol, a weak androgen, used to treat endometriosis and fibrocystic breast disease
ADEs of androgens
Weight gain Decreased breast size Deepening voice Increased libido Increased hair growth
Pharmacokinetics of androgens: Testosterone
Ineffective orally
C17 esters of testosterone are given IM
Transdermal patches, topical g
Pharmacokinetics of androgens: testosterone derivates
Alkylation of the 17 alpha position of
testosterone allows oral administration
-Fluoxymesterone [Androxy]—
hypogonadism or metastatic breast
cancer in the male
-Oxandrolone [Oxandrin]—orally active
testosterone derivative with anabolic
activity 3-13 times that of testosterone;
used for weight gain in those with HIV or
catabolic states; used for osteoporosis
related bone pain
ADEs of androgens in females
masculization, acne, growth
of facial hair, deepening of voice, male
pattern baldness, excess muscle
development, menstrual irregularities
Pregnant women should NOT use because
of possible virilization of the female fetus
ADEs of androgens in males
priapism, impotence, decreased sperm production, gynecomastia, cosmetic changes [like those seen in women], stimulate growth
of the prostate
ADEs of androgens in children
abnormal sexual maturation and growth disturbances from premature closing of epiphyseal plates
General effects of androgens are;
increased LDL,decreased HDL, fluid retention, edema
ADEs of androgens in athletes
In athletes—using anabolic steroids can cause premature closing of
epiphyses of the long bones—which will stunt the growth and interrupt development
High doses may result in reduction of testicular volume, hepatic
abnormalities, increased aggression, major mood disorders
What are antiandrogens
counter male hormonal action by interfering with the synthesis of
androgens or by blocking their receptors
What antiandrogens can you take for prostate cancer
Flutamide [Eulexin], Bicalutamide [Casodex], Enzalutamide [Xtandi], Nilutamide
[Nilandron] act as competitive inhibitors of androgens at the target cell and
taken orally
Antiandrogens use for BPH
Finasteride [Proscar] and Dutasteride [Avodart] inhibit 5 alpha reductase resulting
in decreased formation of DHT
What do progestins in COCs do?
—they suppress LH, FSH and cause the endometrium to be unfavorable for implantation
Other scenarios where COCs can be used
Regulating the menstrual cycle
Reduction of heavy menstrual bleeding
Management of acne
Managing dysmenorrhea
Managing PMS
Reduce risk of ovarian, endometrial and colon cancers
During perimenopause may prevent bone loss and reduce the risk of osteoporosis
Products with Drospirenone—less like to have HTN, more likely to improve mood and lessen weight gain in those with PMS
Overweight patients on COCs are at increased risk for…
stroke, MI and VTE
COC Ring: 1 example
NuvaRing
What are 3 IUDs
Skyla [3 years]
Liletta [3 years]
Mirena [5 years]
Progestin alternatives
Oral Pills-35 mcg daily
Norethindrone
Many brand names—Camila, Errin, Heather, Jencycla, Jolivette, Nora-BE, Ortho Micronor, Nor-QD
Progestin alternatives
Injectable
Medroxyprogesterone acetate given IM every 90 days
Depo-Provera; Depo-subQ Provera 104
Progestin alternatives
Subdermal
Etonogegstrel 68 mg every 3 years
Nexplanon
Nonhormonal contraceptive methods
Vaginal spermicides [nonoxynol-9]
Male condoms
Female condoms
Diaphragm [Rx required]—must be left in place 6°
Cervical Cap [Rx required]—can be left in place 48°
Sponge—must be left in place 6°
Para-Guard Copper T380A IUD [RX required]
Emergency Contraception
3 FDA approved options for EC
Progestin orally in high dose, progestin receptor modulator & Copper IUD Paraguard
High dose estrogen/progestin combinations also can be used, but are not FDA approved—have more S/E and are not as effective as the FDA approved methods
Progestin only options are OTC and are approved for use up to 72 hours after unprotected intercourse—Plan B, One-Step, Next Choice, One Dose, My Way
Contain 1.5 mg of Levonorgestrol
What is the first choice for a woman starting COCs
Cs should be a monophasic product, preferably with a 2nd generation progestin; cycle control may be better for some women with COCs containing 30-35 mcg of ethinyl estradiol
Emergency contraceptive:
Ulipristal [Ella]
nearly 3 times more effective than the OTC options, can be
used up to 120 hours after the unprotected intercourse episode
Requires a prescription
- effective in women up to 194 pounds
Emergency contraceptive:
Ulipristal [Ella]
nearly 3 times more effective than the OTC options, can be
used up to 120 hours after the unprotected intercourse episode
Requires a prescription
- effective in women up to 194 pounds
***OTC EC are only good for up to 154 pounds
Emergency contraceptive:
Copper IUD
it can be inserted up to 5 days after
the unprotected intercourse [will then give long term contraception for 7 years]
What changes cause menopausal symptoms
Changes in estrogen levels due to decreased production by the
ovaries are thought to cause an increase in neurotransmitters [Epinephrine & NE] released from hypothalamus
This lowers the thermoregulatory set point—and then subtle changes in core body temperature can cause sweating and blood
distribution to the periphery
Women who smoke or have a greater body mass experience more vasomotor symptoms
What are approved for use for menopausal vasomotor symptoms
estrogen alone or in combination with
progestin
-used for 5 years or less
Contraindications for estrogen/progestin to be used for vasomotor symptosm
**undiagnosed vaginal bleeding, estrogen dependent malignancy
- Relative contraindications—past DVT, migraines with aura, active endometriosis, severe liver disease, strong FH of breast cancer
17ß estradiol
Estrac
Conjugated estrogens:
premarin
Synthetic conjugated estrogens, A
Cenestin
Synthetic conjugated estrogens, B
Enjuvia
Esterified estrogens
Menest
Estropipate
Ogen
Biodentical hormone therapy
Hormone based medications that are compounded by specialty pharmacies FDA does not recognize this term nor does it approve these hormones for use Formulas are inconsistent Not evidenced based
Nonhormonal options
SSRIs & SNRIs—Paroxetine 7.5 mg daily [Brisdelle] is only nonhormonal FDA approved med for the treatment of menopausal vasomotor symptoms
Clonidine/Gabapentin—neither is FDA approved for vasomotor symptoms
- Clonidine—centrally acting alpha agonist thought to elevate threshold at which the body will develop flushing—perhaps decreasing number of hot flashes;
0.05-.15 mg BID
- Gabapentin—anticonvulsant, helps to manage hot
flashes through an unknown mechanism; 900 mg daily
Drugs to treat vaginal symptoms
Lack of estrogen leads to atrophy of the vaginal tissues
Before menopause, estrogen stimulated exfoliation of the vaginal cells; as the
cells exfoliate, glycogen is released, which is hydrolyzed into glucose
Lactobacilli in the vaginal tissues convert this glucose to lactic acid, which
maintains the vaginal pH at 3.5-4.5; without estrogens, the pH increases to 5-7.5,
lading to symptoms that may include dryness, discomfort itching, burning,
discharge and painful intercourse
What is the main treatment of vaginal symptms
estrogens
Vaginal creams
conjugated estrogen: premarin
estradiol: estrace
Vaginal tables
estradiol: vagifem
vaginal ring
estradiol: estring
Ospemifene
Osphena is FDA approved Oral estrogen receptor agonist/antagonist, for the treatment of moderate to severe dyspareunia 60 mg daily PO with food No dosage adjustments for renal impairment or hepatic disease Fluconazole and Rifampin cannot be taken while on Osphenia Side effects—hot flashes, vaginal discharge, muscle spasms and hyperhidrosis
Vaginal options:
Lubricants—can relieve sx of dyspareunia—use immediately before intercourse
Water based or silicone based
Yes, Astro-Glide, Replens
Moisturizers—should be used routinely; at least every 3-4 days
Replens moisturizer, Luvena, KY moisturizer
Women should be encouraged to continue
sexual activity—helps maintain active blood
flow to the vagina, which can help with
lubrication and prevent atrophy
Bacterial Disease: Chancroid
caused by: Haemophillius ducreyi
RX:Prescriptions to Treat Zithromax 1 gram PO; Rocephin 250 mg IM
Bacterial Disease: chlamydia
caused by: trachomatis
RX: Zithromax 1 gram PO; Doxycycline 100 mg BID x 7 days
Bacterial Disease: Donovanosis
Caused By: Granuloma inguinale
Calymmatobacterium granulomatis
RX: Zithromax 1 gram PO x 2 1 days; Doxycycline 100 mg BID x
21days
Bacterial Disease: Gonorrhea
Caused By: Neisseria gonorrhoeae PO
RX: 250 m g IM + Zithromax 1 gram PO
Suprax 400 mg PO + Zithromax 1 gram PO
Bacterial Disease: Lymphogranuloma venereum
Caused By: Chlamydia trachomatis [serotypes L1, L2, L3]
RX: Zithromax 1 gram PO; Doxycycline 100 mg BID x 7 days
Bacterial Disease: Nongonococcal urethritis
Caused By: Ureaplasma urealytium
Mycoplasma hominis
RX: Zithromax 1 gram or Doxycycline 100 mg BID for 7 days OR Clindamycin 450 mg q 6° for 7days Levaquin 500 mg for 7 days Ofloxacin 300 mg BID for 7 days
Bacterial Disease: Syphilis
Caused By: treponema pallidum
RX: r Aq. Penicillin G 2.4 million units IM
Doxycycline 100 mg BID for 14 days
[both +/- Prednisone 40-60 mg daily for 3 days]
Bacterial Disease: Bacterial vaginosis
Caused By: Gardenerella vaginalis
Mobiluncus species
RX:
Flagyl 500 mg PO BID x 7 days
Flagyl gel 5 g. vaginally @ HS x 5d
Viral Disease: CMV
Caused By: Cytomegalovirus
RX: Reassurance
If treatment indicated—Foscarnet or Cidofovir [with ID
consultation]
Viral Disease: HSV
Caused By: Herpes simplex
RX: Acyclovir 400 mg TID for 7-10 days or 200 mg 5 times/day for
7-10 days
Valcyclovir 1000 mg BID for 7-10 days
Famcyclovir 250 mg TID for 7-10 days
Viral Disease: HPV
Caused By: Human papilloma
RX:
-Podofilox 0.5% BID for 3 days [can repeat each week for 4 cycles]
- Imiquimod 5% TIW @ HS for 16 weeks
- Sinecatechins [Veregen] 15% ointment TID for 16 weeks
- Local therapies may be indicated
Viral Disease: Molluscum contagiosum
REFER TO DERMATOLOGY
Caused By: Pox virus
RX: Glycolic acid topically Imiquimod 5% daily [leave on 6-10°] Tretinoin topical [0.1% cream or 0.025% gel] @ HS Salicylic acid [50-80% compounded] K+ hydroxide topical [compounded
Which of the following methods of hormonal contraceptive has the
lowest failure rate with typical use?
Levonorgestrel IUD
When prescribing the sponge as a contraceptive option, the NP
should counsel the woman that after intercourse, the contraceptive
sponge must be left in place for:
6 HOURS
The estrogen component of combines oral contraceptives:
Inhibits FSH production
A 55 y/o woman reports that she had her LMP approximately 14 months ago. She had breast cancer that was treated with XRT and chemotherapy when she was 45 years old. She has no other
pertinent PMH or other surgical history. Her chief complaint is sever hot flashes that interfere with her ability to work. Which treatment option would be best for this patient?
Paroxetine
A 26 y/o female is using injectable MPA as a method of contraception. Which of the following adverse effects is a concern
if she wishes to use this therapy long term?
Osteoporosis
