Drugs To Use For Women’s Health Issues Flashcards
Estrogens
Estradiol
most potent estrogen; secreted in the ovary by the premenopausal woman
Estrogens
Estrone
metabolite of estradiol; 1/3 of the potency of Estradiol; primary estrogen in the post- menopausal woman; generated from conversion of androstenedione in the peripheral and adipose tissues
Estrogens
Estriol
another metabolite of Estradiol; must less potent than Estradiol; principal estrogen produced by the placenta
Estrogens
Conjugated Equine Estrogen
sulfate esters of Estrone + Equilin is a common oral estrogen used as HRT [Premarin]
Estrogens
Other estrogens
Plant derived estrogens
Synthetic estrogens—ethinyl estradiol—undergoes less liver metabolism than naturally occurring estrogens, so can be safely used at low doses
Nonsteroidal compounds that bind to estrogen receptors [have both estrogen and anti-estrogen effects] are called SERMs [Tamoxifen, Raloxifene (Envista)]
Estrogens
MOA and Therapeutic Uses
MOA—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
Estrogens Androgens
Other Uses
Contraception
Combination of estrogen and
progestogen is used
-Orally
-Transdermal
-Vaginal
Other Entities
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
Pharmacokinetics
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
Pharmacokinetics
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
Pharmacokinetics
Estrogens
Metabolism
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
Estrogens
Adverse Effects
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
-Tamoxifen
-Toremifene [Fareston]
-Raloxifene [Evista]
-Clomiphene [Clomid]
-Ospemifene [Osphena]
Selective Estrogen Receptor Modulators
Mechanism of Action
Tamoxifen, Toremifene and Raloxifene compete with estrogen for binding to the estrogen receptor in the breast tissue
-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 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
SERM
Uses and Pharmacokinetics
Tamoxifen—metastatic breast cancer; add
on therapy after mastectomy or XRT for
breast cancer; prevention of breast cancer in
those at high risk
Raloxifene—prevention of breast cancer in
those at high risk; prevention and treatment
of osteoporosis in postmenopausal women
Clomiphene—used for infertility from
anovulatory cycles
Ospemifene—treatment of dyspareunia from menopause
SERM
Pharmacokinetics
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
Progestogens
Progesterone—natural progestogen; produced in response to LH in women & by the testes in men; also produced by adrenal cortex in both sexes
Progestogens
MOA
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
Progestogens
Therapeutic Uses
Contraception
Treatment of hormone deficiency
Control of DUB, 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]
Progestogens
Pharmacokinetics
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
Progestogens
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
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
Contraceptives
Interference with ovulation—most common
pharmacologic intervention for preventing
pregnancy
Major Classes of Contraceptives
Combined Oral Contraceptives [COC]
Most common estrogen in COCs—ethinyl estradiol
Most common progestins in COCs—norethindrone, norethindrone acetate, levonorgestrel, desogestrel, norgestimate and drosperidone
Combined Oral Contraceptives [COC]
Combination on an estrogen & a progestin
Monophasic combination pills contain a constant dose of estrogen and progestin over 21-24 days
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
Patches/Rings
Estrogen Transdermal Patch
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
Patches/Rings
Estrogen 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
Progestins
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
Progestins
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
IUDs
Levonorgestrel releasing IUD system
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°
Progestin only EC better tolerated
than estrogen/progestin
combinations
Alternative
-Progesterone agonist/antagonist— Ulipristal [Ella] can be used as EC within 5 days of unprotected intercourse
Emergency Contraception
MOA
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 Estrogens
Breast fullness
Fluid retention
Headache
Nausea
Elevated BP
Thromboembolism
Thrombophlebitis
MI
Stroke
ADEs of Progestins
Depression
Changes in libido
Hirsutism
Acne
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
Androgens
MOA
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
Androgens
Therapeutic Uses
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
Androgens
ADEs
Weight gain
Decreased breast size
Deepening voice
Increased libido
Increased hair growth
Pharmacokinetic
Testosterone
Ineffective orally
C17 esters of testosterone are given IM
Transdermal patches, topical gels and
buccal tablets are available
Pharmacokinetics
Testosterone Derivatives
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
Androgens
Adverse Effects
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
In males—priapism, impotence,
decreased sperm production, gynecomastia, cosmetic changes [like those seen in women], stimulate growth of the prostate
In children—abnormal sexual maturation and growth disturbances from premature closing of epiphyseal plates
General effects—increased LDL,
decreased HDL, fluid retention,
edema
Androgens
Adverse Effects
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
Antiandrogens
Antiandrogens counter male hormonal action by interfering with the synthesis of
androgens or by blocking their receptors
Finasteride [Proscar] and Dutasteride [Avodart] inhibit 5 alpha reductase resulting
in decreased formation of DHT—both are used to treat BPH
Flutamide [Eulexin], Bicalutamide [Casodex], Enzalutamide [Xtandi], Nilutamide
[Nilandron] act as competitive inhibitors of androgens at the target cell and
taken orally for the treatment of prostate cancer
Writing Prescriptions for Estrogens,
Progestins, Androgens
COCs
In the US, most COCs contain ethinyl estradiol [one contains estradiol valerate]
Estrogens regulate endometrial proliferation and prevent ovulation and prevent estrogen
deficiency induced by progestin (important)
9 different progestins used in COCs in the US—they are the main contraceptive
component in COCs—they suppress LH, FSH and cause the endometrium to be
unfavorable for implantation
Progestins
1st Generation
-Norethindrone
-Norethindrone Acetate
2nd Generation
-Levonorgestrel
-Norgestrel
3rd Generation
-Destrogestrel
-Norgestimate
Others
-Drospirenone
-Dienogest
**First choice for a woman starting COCs 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 ethinyl estradiol
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
COCs
Contraindications/Risk Factors
ACOG states that COC is contraindicated for women 35 and older who smoke
Risk factors for stroke, MI and VTE are increased in patient’s that are overweight and obese
COCs
Rings/Patches/IUDs
Rings
-NuvaRing
Patches
-Xulane
-Ortho Evra
IUDs 3 hormonal options-Levonorgestrel coated 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
Injectable
-Medroxyprogesterone acetate given IM every 90 days
-Depo-Provera; Depo-subQ Provera 104
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
Emergency Contraception
Prescription options include insertion of a copper IUD—it can be inserted up to 5 days after the unprotected intercourse [will then give long term contraception for 7 years]
Other option is 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
Oral forms of EC ARE affected by weight—OTC options successfully in women up to 154 pounds; Ella effective in women up tot 194 pounds
Drugs to Manage Menopausal Symptoms
Bazedoxifene/Conjugated Estrogens [DuaVee]
20 mg of Bazedoxifene + .45 mg of conjugated estrogen
-SERM in combination with estrogen for treating moderate to severe vasomotor symptoms associated with menopause in women with a uterus
-Bazedoxifene acts as an antagonist for estrogen receptors in uterine tissue, so when given in combination with estrogen it opposes the effects of estrogens on the uterus
-Bazedoxifene [Viviant] is also approved for preventing postmenopausal osteoporosis in women with a uterus
Side Effects—muscle spasms, diarrhea,, nausea, indigestion, upper abdominal pain [all >10%]
Drugs to Treat Menopausal Symptoms
Bioidentical 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 HC 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 Menopausal Symptoms
Phytoestrogens and Black Cohosh
Phytoestrogens are plant based estrogens—alternative treatments despite a LACK of evidence supporting their use; Isoflavones [one type of phytoestrogens] are derived from soy or red clover extract—not EB
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, leading to symptoms that may include dryness, discomfort itching, burning, discharge and painful intercourse
Estrogens are the main treatment of vaginal symptoms—four local estrogens are
FDA approved—2 creams, one ring and one tablet
Drugs to Treat Vaginal Symptoms
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
Drugs to Treat Vaginal Symptoms
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
Drugs to Manage Infections of the
Genitourinary System
Bacterial Etiologies
Chancroid
Haemophillius ducreyi
Zithromax 1 gram PO; Rocephin 250 mg IM
Bacterial Etiologies
Chlamydia
Chlamydia trachomatis
Zithromax 1 gram PO; Doxycycline 100 mg BID x 7 days
Bacterial Etiologies
Donovanosis
Granuloma inguinale
Calymmatobacterium granulomatis
Zithromax 1 gram PO x 2 1 days; Doxycycline 100 mg BID x 21days
Bacterial Etiologies
Gonorrhea
Neisseria gonorrhoeae
Rocephin 250 m g IM + Zithromax 1 gram PO
Suprax 400 mg PO + Zithromax 1 gram PO
Bacterial Etiologies
Lymphogranuloma venereum
Chlamydia trachomatis [serotypes
L1, L2, L3]
Zithromax 1 gram PO; Doxycycline 100 mg BID x 7 days
Bacterial Etiologies
Nongonococcal urethritis
Ureaplasma urealytium
Mycoplasma hominis
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 Etiologies
Syphilis
Treponema pallidum
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 Etiologies
Bacterial vaginosis
Gardenerella vaginalis
Mobiluncus species
Flagyl 500 mg PO BID x 7 days
Flagyl gel 5 g. vaginally @ HS x 5d
Viral Etiologies
CMV
Cytomegalovirus Reassurance
If treatment indicated—Foscarnet or Cidofovir [with ID consultation]
Viral Etiologies
HSV
Herpes simplex
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 Etiologies
HPV
Human papilloma 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 Etiologies
Molluscum
contagiosum
Pox virus
Curettage/Cryo +/- Cantharidin [derm specialist only]
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]
Protozoal Etiologies
Trichomonas
Trichomonas vaginalis
Flagyl 2 grams PO or
Tinidazole 2 grams PO with
food
