FEMALE HORMONE MEDICATIONS

All dosing is for ADULTS unless otherwise specified
PRICING INFO


References:

  • References PMID 25423325, PMID 25210448, PMID 10874566
SERM ACTIVITY TABLE
SERM Product Endometrium Vagina Breast Bone
formation
Hypothalamus
Bazedoxifene Duavee® Neutral to
Antagonist
No data Neutral to
Antagonist
Agonist ?
Clomiphene Clomid® Antagonist ? ? Agonist Antagonist
Ospemifene Osphena® Neutral to
Partial agonist
Agonist Antagonist Agonist ?
Raloxifene Evista® Neutral to
Partial agonist
Neutral Antagonist Agonist ?
Tamoxifen Nolvadex® Neutral to
Agonist
Agonist Antagonist Agonist ?

Drug Dosage forms Dosing Other / Price
Cenestin®

conjugated estrogens
Tablet
  • 0.30 mg
  • 0.45 mg
  • 0.625 mg
  • 0.90 mg
  • 1.25 mg
Menopausal vasomotor symptoms
  • Starting: 0.45 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.30 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
Other
  • May take without regard to food
  • Cenestin contains a blend of 9 synthetic estrogenic substances

Price
  • No generic
  • 30 tablets - $$$
Enjuvia®

conjugated estrogens
Tablet
  • 0.30 mg
  • 0.45 mg
  • 0.625 mg
  • 0.90 mg
  • 1.25 mg
Menopausal vasomotor symptoms
  • Starting: 0.30 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.30 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
Other
  • May take without regard to food
  • Enjuvia contains a blend of 10 synthetic estrogenic substances

Price
  • No generic
  • 30 tablets - $$
Premarin®

conjugated estrogens
Tablet
  • 0.30 mg
  • 0.45 mg
  • 0.625 mg
  • 0.90 mg
  • 1.25 mg
Menopausal vasomotor symptoms
  • Starting: 0.30 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
  • May be given continuously or in cyclical regimens (25 days on drug followed by 5 days off)
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.30 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
  • May be given continuously or in cyclical regimens (25 days on drug followed by 5 days off)
Prevention of postmenopausal osteoporosis
  • Dosing: 0.30 mg once daily
  • May be given continuously or in cyclical regimens (25 days on drug followed by 5 days off)
Hypogonadism
  • Dosing: 0.30 - 0.625 mg once daily given cyclically (3 weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
Female castration or primary ovarian failure
  • Dosing: 1.25 mg once daily given cyclically (3 weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
Palliative metastatic breast cancer treatment
  • Dosing: 10 mg three times a day for at least 3 months
Palliative advanced prostate cancer treatment
  • Dosing: 1.25 - 2.5 mg three times a day
Other
  • May take without regard to food
  • Premarin contains a mixture of conjugated estrogens purified from pregnant mares' urine

Price
  • No generic
  • 30 tablets - $$$

Drug Dosage forms Dosing Other / Price
Estrace®

estradiol
Tablet
  • 0.50 mg
  • 1.0 mg
  • 2.0 mg
Menopausal vasomotor symptoms
  • Dosing: 1 - 2 mg once daily given cyclically (3 weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Menopausal vulvar and vaginal atrophy
  • Dosing: 1 - 2 mg once daily given cyclically (3 weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Prevention of postmenopausal osteoporosis
  • Dosing: 0.50 - 2 mg once daily
  • Lowest effective dose has not been determined
Hypoestrogenism due to hypogonadism, castration, or primary ovarian failure
  • Dosing: 1 - 2 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
Palliative metastatic breast cancer treatment
  • Dosing: 10 mg three times a day for at least 3 months
Palliative advanced prostate cancer treatment
  • Dosing: 1 - 2 mg three times a day
Other
  • May take without regard to food

Price
  • Generic available
  • 30 tablets - $

Drug Dosage forms Dosing Other / Price
Menest®

(esterified estrogens)
Tablet
  • 0.30 mg
  • 0.625 mg
  • 1.25 mg
  • 2.5 mg
Menopausal vasomotor symptoms
  • Dosing: 1.25 mg once daily given cyclically (three weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
  • If patient is still menstruating, start on Day 5 of bleeding
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.30 - 1.25 mg once daily given cyclically (three weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Hypogonadism
  • Dosing: 2.5 - 7.5 mg/day given in divided doses for 20 days followed by 10 days off
  • Titrate to desired effect. Use lowest effective dose.
Female castration or primary ovarian failure
  • Dosing: 1.25 mg once daily given cyclically (three weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
Palliative metastatic breast cancer treatment
  • Dosing: 10 mg three times a day for at least 3 months
Palliative advanced prostate cancer treatment
  • Dosing: 1.25 - 2.5 mg three times a day
Other
  • May take without regard to food
  • Esterified estrogens are a mixture of the sodium salts of the sulfate esters of the estrogenic substances, principally estrone, that are of the type excreted by pregnant mares

Price
  • No generic
  • 30 tablets - $$

Drug Dosage forms Dosing Other / Price
Ogen®

estropipate
Tablet
  • 0.75 mg
  • 1.5 mg
  • 3.0 mg
Menopausal vasomotor symptoms
  • Dosing: 0.75 - 6 mg once daily given cyclically (three weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
  • If patient is still menstruating, start on Day 5 of bleeding
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.75 - 6 mg once daily given cyclically (three weeks on followed by one week off)
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Prevention of postmenopausal osteoporosis
  • Dosing: 0.75 mg once daily for 25 days of a 31-day cycle each month
Hypogonadism
  • Dosing: 1.5 - 9 mg once daily given for the first 3 weeks of a cycle followed by 8 - 10 days off
  • Titrate to desired effect. Use lowest effective dose.
Female castration or primary ovarian failure
  • Dosing: 1.5 - 9 mg once daily given for the first 3 weeks of a cycle followed by 8 - 10 days off
  • Titrate to desired effect. Use lowest effective dose.
Other
  • May take without regard to food
  • Estropipate is a natural estrogenic substance prepared from purified crystalline estrone, solubilized as the sulfate and stabilized with piperazine

Price
  • Generic available
  • 30 tablets - $

Drug Dosage forms Dosing Other / Price
Osphena®

ospemifene
Tablet
  • 60 mg
Dyspareunia due to menopause
  • Dosing: 60 mg once daily with food
  • Use for shortest duration necessary
Other
  • Take with food. Food increases absorption.
  • See ospemifene below for contraindications, precautions, side effects, and drug interactions
  • Ospemifene is a selective estrogen receptor modulator (SERM). It has an agonistic effect on the endometrium. A progestin should be considered in women with a uterus. See for more.

Price
  • No generic
  • 30 tablets - $$$$

Drug Dosage forms Dosing Other / Price
Alora®

estradiol
Patch
  • 0.025 mg/24 hour
  • 0.050 mg/24 hour
  • 0.075 mg/24 hour
  • 0.10 mg/24 hour
Menopausal vasomotor symptoms
  • Dosing: 0.050 mg/day patch applied twice weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
  • In women with an intact uterus, may be given cyclically (3 weeks on followed by 1 week off)
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.050 mg/day patch applied twice weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
  • In women with an intact uterus, may be given cyclically (3 weeks on followed by 1 week off)
Hypogonadism, female castration, primary ovarian failure
  • Dosing: 0.050 mg/day patch applied twice weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Prevention of postmenopausal osteoporosis
  • Dosing: 0.025 mg/day patch applied twice weekly
  • 0.025 mg/day is the lowest dose that has been shown to be effective
Other
  • Recommended application site is lower abdomen. The upper quadrant of the buttocks or outer aspect of the hip may also be used. Rotate application site allowing 1 week before using same site again. DO NOT apply to breasts.
  • In women who are switching from oral estrogens, allow 1 week from discontinuing pills before applying patch unless symptoms return

Price
  • No generic
  • 8 patches - $$
Climara®

estradiol
Patch
  • 0.025 mg/24 hour
  • 0.0375 mg/24 hour
  • 0.050 mg/24 hour
  • 0.060 mg/24 hour
  • 0.075 mg/24 hour
  • 0.10 mg/24 hour
Menopausal vasomotor symptoms
  • Dosing: 0.025 mg/day patch applied once weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.025 mg/day patch applied once weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Hypogonadism, female castration, primary ovarian failure
  • Dosing: 0.025 mg/day patch applied once weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Prevention of postmenopausal osteoporosis
  • Dosing: 0.025 mg/day patch applied once weekly
Other
  • Recommended application site is lower abdomen or upper quadrant of the buttocks. Rotate application site. DO NOT apply on or near breasts.
  • In women who are switching from oral estrogens, allow 1 week from discontinuing pills before applying patch unless symptoms return

Price
  • Generic available
  • 4 patches - $-$$
Menostar®

estradiol
Patch
  • 0.014 mg/24 hour
Prevention of postmenopausal osteoporosis
  • Dosing: 0.014 mg/day patch applied once weekly
  • In women with a uterus, it is recommended that they receive a progestin for at least 14 days every 6 to 12 months and undergo an endometrial biopsy at yearly intervals or as clinically indicated
Other
  • Recommended application site is lower abdomen. Rotate application site. DO NOT apply on or near breasts.

Price
  • No generic
  • 4 patches - $$$
Minivelle®

estradiol
Patch
  • 0.025 mg/24 hour
  • 0.0375 mg/24 hour
  • 0.050 mg/24 hour
  • 0.075 mg/24 hour
  • 0.10 mg/24 hour
Menopausal vasomotor symptoms
  • Dosing: 0.0375 mg/day patch applied twice weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Prevention of postmenopausal osteoporosis
  • Dosing: 0.025 mg/day patch applied twice weekly
Other
  • Recommended application site is lower abdomen or buttocks. Rotate application site allowing 1 week before using same site again. DO NOT apply to breasts.

Price
  • No generic
  • 8 patches - $$$
Vivelle-dot®

estradiol
Patch
  • 0.025 mg/24 hour
  • 0.0375 mg/24 hour
  • 0.050 mg/24 hour
  • 0.075 mg/24 hour
  • 0.10 mg/24 hour
Menopausal vasomotor symptoms
  • Dosing: 0.0375 mg/day patch applied twice weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
  • In women with an intact uterus, may be given cyclically (3 weeks on followed by 1 week off)
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.0375 mg/day patch applied twice weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
  • In women with an intact uterus, may be given cyclically (3 weeks on followed by 1 week off)
Hypogonadism, female castration, primary ovarian failure
  • Dosing: 0.0375 mg/day patch applied twice weekly
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Prevention of postmenopausal osteoporosis
  • Dosing: 0.025 mg/day patch applied twice weekly
  • In women with an intact uterus, may be given cyclically (3 weeks on followed by 1 week off)
Other
  • Recommended application site is the trunk of the body including the abdomen and buttocks. Rotate application site allowing 1 week before using same site again. DO NOT apply to breasts.
  • In women who are switching from oral estrogens, allow 1 week from discontinuing pills before applying patch unless symptoms return

Price
  • Generic available
  • 8 patches - $$

Drug Dosage forms Dosing Other / Price
Estrace® vaginal cream

estradiol
Vaginal cream
  • 0.01% cream
  • Comes in 42.5 gram tubes
  • Comes with applicator that delivers 1, 2, 3, and 4 gram doses
Vulvar and vaginal atrophy
  • Starting: 2 - 4 grams intravaginally for 1 - 2 weeks, then reduce to half initial dose for another 1 - 2 weeks
  • Maintenance: 1 gram one to three times a week
  • Use lowest effective dose
  • Reevaluate need for therapy periodically
Other
  • Estrace vaginal cream is absorbed systemically and therefore carries all the same risks of oral Estrace
  • The North American Menopause Society states that progesterone therapy is not necessary with low-dose vaginal estrogen therapy in women who have a uterus [4]

Price
  • No generic
  • 42.5 gram tube - $$$$
Premarin® vaginal cream

conjugated estrogens
Vaginal cream
  • 0.625 mg/gram
  • Comes in 30 gram tube
  • Comes with applicator that delivers 0.5, 1, 1.5, and 2 gram doses
Atrophic vaginitis and kraurosis vulvae
  • Starting: 0.5 grams intravaginally in a cyclic regimen (daily for 21 days followed by 7 days off)
  • Dose may be titrated up to 2 grams/day to achieve desired effect. Use lowest effective dose.
Dyspareunia due to menopause
  • Starting: 0.5 grams intravaginally in a twice weekly (for example Monday and Thursday) continuous regimen or in a cyclic regimen (daily for 21 days followed by 7 days off)
Other
  • Premarin vaginal cream is absorbed systemically and therefore carries all the same risks of oral Premarin
  • Premarin vaginal cream may weaken latex barrier contraceptive methods (e.g. condom)
  • Premarin vaginal cream contains a mixture of conjugated estrogens blended to represent the estrogen content of a pregnant mares' urine
  • The North American Menopause Society states that progesterone therapy is not necessary with low-dose vaginal estrogen therapy in women who have a uterus [4]

Price
  • No generic
  • 30 gram tube - $$$$

Drug Dosage forms Dosing Other / Price
Elestrin® gel

estradiol
Gel pump
  • 0.06% gel
  • Each pump delivers 0.87 grams of gel which contains 0.52 mg of estradiol
  • Comes in 35 gram pump that delivers 30 metered doses
Menopausal vasomotor symptoms
  • Starting: 0.87 grams (0.52 mg of estradiol) once daily
  • Titrate to desired effect. Use lowest effective dose.
  • Apply a thin layer to upper arm
Other
  • Prime pump before first use
  • Wash hands after applying
  • Apply after bathing. Allow 2 hours after applying before swimming.
  • Sunscreen may increase absorption. Do not apply sunscreen until at least 25 minutes after applying Elestrin. Do not apply sunscreen to the Elestrin application site for 7 or more days in a row.
  • Gel may be transferred through skin contact to other people. Cover application site after it dries.

Price
  • No generic
  • 1 pump - $$
Estrogel® gel

estradiol
Gel pump
  • 0.06% gel
  • Each pump delivers 1.25 grams of gel which contains 0.75 mg of estradiol
  • Comes in a 50 gram pump that delivers 32 doses
Menopausal vasomotor symptoms
  • Dosing: 1.25 grams (0.75 mg of estradiol) once daily
  • Apply a thin layer over the entire arm on the inside and outside from wrist to shoulder
Menopausal vulvar and vaginal atrophy
  • Dosing: 1.25 grams (0.75 mg of estradiol) once daily
  • Apply a thin layer over the entire arm on the inside and outside from wrist to shoulder
Other
  • Pump must be primed 3 times before first use
  • Use of lotion one hour after application increases estradiol absorption
  • Wash hands after applying
  • Apply after bathing. Do not swim for as long as possible after applying.
  • Gel may be transferred through skin contact to other people. Cover application site after it dries.

Price
  • No generic
  • 1 pump - $$$
Divigel® gel

estradiol
Gel packets
  • Comes in individual packets available in 3 doses
  • 0.25 mg packet
  • 0.50 mg packet
  • 1.0 mg packet
  • Comes in cartons of 30 packets
Menopausal vasomotor symptoms
  • Starting: 0.25 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
  • Apply to skin of upper thigh. Alternate between thighs. Application surface area should be 5 - 7 inches.
  • Do not wash application site within 1 hour of applying gel
  • Allow gel to dry before dressing
Other
  • Sunscreens and lotions may increase the absorption of estradiol
  • Apply after bathing. Allow application to dry before swimming.
  • Gel may be transferred through skin contact to other people. Cover application site after it dries.

Price
  • No generic
  • 30 packets - $$$

Drug Dosage forms Dosing Other / Price
Estring®
vaginal ring

estradiol
Vaginal ring
  • Each ring contains 2 mg of estradiol
Menopausal vulvar and vaginal atrophy
  • Dosing: 1 ring placed intravaginally every 3 months
  • Ring is placed as high as possible into the upper one-third of the vaginal vault
  • Reevaluate need for therapy periodically
  • If ring falls out, rinse with lukewarm water and reinsert
  • Estring should not be felt when placed properly
Other
  • Systemic absorption of estradiol does occur
  • Estring may be expelled during bowel movement straining
  • Estring may not be suitable for women with narrow, short, or stenosed vaginas
  • Remove Estring if vaginal infection occurs and reinsert after infection clears
  • The North American Menopause Society states that progesterone therapy is not necessary with low-dose vaginal estrogen therapy in women who have a uterus [4]

Price
  • No generic
  • 1 ring - $$$$
Femring®
vaginal ring

estradiol
Vaginal ring
  • 0.05 mg/day ring
  • 0.10 mg/day ring
Menopausal vasomotor symptoms
  • Starting: 0.05 mg/day ring intravaginally every 3 months
  • Titrate to desired effect. Use lowest effective dose.
  • Ring is placed as high as possible into the upper vagina
  • Reevaluate need for therapy periodically
  • If ring falls out, rinse with lukewarm water and reinsert
  • Femring should not be felt when placed properly
Menopausal vulvar and vaginal atrophy
  • Starting: 0.05 mg/day ring intravaginally every 3 months
  • Titrate to desired effect. Use lowest effective dose.
  • Ring is placed as high as possible into the upper vagina
  • Reevaluate need for therapy periodically
  • If ring falls out, rinse with lukewarm water and reinsert
  • Femring should not be felt when placed properly
Other
  • Systemic absorption of estradiol does occur
  • Femring may not be suitable for women with narrow, short, or stenosed vaginas
  • Femring may be expelled during bowel movement straining
  • Femring may be left in place during local treatment of a vaginal infection
  • The North American Menopause Society states that progesterone therapy is not necessary with low-dose vaginal estrogen therapy in women who have a uterus [4]

Price
  • No generic
  • 1 ring - $$$$
Vagifem®
vaginal tablet

estradiol
Vaginal tablet
  • 10 mcg
  • Each tablet comes with single-use applicator
Menopausal atrophic vaginitis
  • Starting: 10 mcg tablet inserted intravaginally once daily for 2 weeks, followed by 1 tablet twice weekly (for example Tuesday and Friday)
Other
  • Systemic absorption of estradiol does occur
  • The North American Menopause Society states that progesterone therapy is not necessary with low-dose vaginal estrogen therapy in women who have a uterus [4]

Price
  • No generic
  • 8 tablets - $$$-$$$$
Intrarosa®
vaginal insert

prasterone
Vaginal insert
  • Each insert contains 6.5 mg of prasterone
  • Comes in box with 28 bullet-shaped inserts and applicator
Moderate to severe dyspareunia
  • Administer one insert once daily at bedtime using the provided applicator
Other
  • Prasterone is also known as dehydroepiandrosterone (DHEA)
  • DHEA is a weak androgen produced by the adrenal glands. In certain tissues, it is converted into active metabolites of estrogen and testosterone. Its mechanism in treating dyspareunia is unknown.
  • Intrarosa is absorbed systemically and in pharmacokinetic studies, patients receiving Intrarosa had slight increases in estradiol and testosterone levels
  • See Intrarosa below for contraindications, precautions, side effects, and drug interactions

Price
  • No generic
  • 28 inserts - $$$$

Drug Dosage forms Dosing Other / Price
Evamist®
spray

estradiol
Spray
  • Each spray contains 1.53 mg of estradiol
  • Comes in 8.1 ml spray bottle that delivers 56 sprays
Menopausal vasomotor symptoms
  • Dosing: 1 - 3 sprays once daily
  • Titrate to desired effect. Use lowest effective dose.
  • Spray on inner surface of forearm starting at elbow. Do not overlap sprays.
  • Allow spray to dry for 2 minutes before covering with clothing
  • Do not wash spray site for at least one hour
Other
  • Spray bottle should be primed 3 times before first use
  • Spray may be transferred through skin contact to other people. Cover application site after it dries.
  • Sunscreen applied 1 hour after Evamist may reduce absorption

Price
  • No generic
  • 1 bottle - $$$

Drug Dosage forms Dosing Other / Price
Aygestin®

norethindrone
Tablet
  • 5 mg
Secondary amenorrhea and abnormal uterine bleeding
  • Dosing: 2.5 - 10 mg once daily for 5 - 10 days
  • Withdrawal bleeding usually occurs within 3 - 7 days after stopping norethindrone
  • Endometrium should be adequately primed with endogenous or exogenous estrogen
  • See abnormal uterine bleeding for more
Endometriosis
  • Starting: 5 mg once daily for 2 weeks. Increase dose by 2.5 mg/day every 2 weeks until 15 mg/day is reached.
  • Continue therapy for 6 - 9 months as tolerated
Other
  • Manufacturer makes no specific recommendation regarding food

Price
  • Generic available
  • 30 tablets - $-$$
Prometrium®

progesterone
Capsule
  • 100 mg
  • 200 mg
Secondary amenorrhea
  • Dosing: 400 mg once daily at bedtime for 10 days
Prevention of endometrial hyperplasia in women receiving estrogens
  • Dosing: 200 mg once daily at bedtime for 12 sequential days out of each 28-day cycle
Other
  • Prometrium contains peanut oil. PATIENTS WITH PEANUT ALLERGY SHOULD NOT TAKE.
  • Prometrium may cause dizziness and drowsiness. Take at bedtime.
  • Food increases absorption. Manufacturer makes no specific recommendation regarding food.

Price
  • Generic available
  • 30 capsules - $$-$$$
Provera®

medroxyprogesterone
Tablet
  • 2.5 mg
  • 5 mg
  • 10 mg
Secondary amenorrhea
  • Dosing: 5 - 10 mg once daily for 5 - 10 days
  • A dose for inducing an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen is 10 mg once daily for 10 days
  • Withdrawal bleeding usually occurs within 3 - 7 days after stopping medroxyprogesterone
Abnormal uterine bleeding
  • Dosing: 5 - 10 mg once daily for 5 - 10 days starting on the calculated 16th or 21st day of the menstrual cycle
  • To produce an optimum secretory transformation of an endometrium that has been adequately primed with either endogenous or exogenous estrogen, 10 mg of Provera daily for 10 days beginning on the 16th day of the cycle is suggested
  • Withdrawal bleeding usually occurs within 3 - 7 days after stopping medroxyprogesterone
  • See abnormal uterine bleeding for more
Prevention of endometrial hyperplasia in women receiving estrogens
  • Dosing: 5 - 10 mg once daily for 12 - 14 consecutive days each month. Dosing may begin on the first or 16th day of each cycle.
  • Use lowest effective dose
Other
  • Food increases absorption. Manufacturer makes no specific recommendation regarding food.

Price
  • Generic available
  • 30 tablets - $

Drug Dosage forms Dosing Other / Price
Crinone®
gel

progesterone
Gel
  • 4% gel (45 mg per applicator)
  • 8% gel (90 mg per applicator)
  • Comes in single-use vaginal applicator that contains 1.45 grams of gel
Secondary amenorrhea
  • Starting: 45 mg intravaginally every other day for 6 doses
  • If 4% gel does not work, may increase to 8%
  • Dosage increases can only be accomplished by increasing the strength (4% to 8%). Administering more gel does not increase absorption.
Assisted reproductive technology
  • Supplementation: 90 mg once daily
  • Replacement: 90 mg twice daily
  • If pregnancy occurs, may continue for up to 10 - 12 weeks
Other
  • Do not administer other local vaginal products within 6 hours of Crinone gel
  • Small, white globules may appear as a vaginal discharge after usage

Price
  • No generic
  • 6 applicators - $$$

Drug Dosage forms Dosing Other / Price
Activella®
Mimvey®
Lopreeza®
Amabelz®

estradiol + norethindrone
Tablet
  • Estradiol : Norethindrone
    • 0.5 mg : 0.1 mg
    • 1 mg : 0.5 mg
Menopausal vasomotor symptoms
  • Dosing: 1 tablet once daily
  • Titrate to desired effect. Use lowest effective dose.
Menopausal vulvar and vaginal atrophy
  • Dosing: 1 mg/0.5 mg once daily
Prevention of postmenopausal osteoporosis
  • Dosing: 1 tablet once daily
  • Titrate to desired effect. Use lowest effective dose.
Other
  • See estrogens below for side effects, contraindications, precautions, and drug interactions
  • See progestins below for side effects, contraindications, precautions, and drug interactions

Price
  • Generic available
  • 28 tablets - $$
Angeliq®

drospirenone + estradiol
Tablet
  • Drospirenone : Estradiol
    • 0.25 mg : 0.5 mg
    • 0.5 mg : 1.0 mg
Menopausal vasomotor symptoms
  • Dosing: 0.25/0.5 - 0.5/1 mg once daily
  • Titrate to desired effect. Use lowest effective dose.
Menopausal vulvar and vaginal atrophy
  • Dosing: 0.5/1 mg once daily
Other
  • See estrogens below for side effects, contraindications, precautions, and drug interactions
  • See progestins below for side effects, contraindications, precautions, and drug interactions
  • Angeliq contains drospirenone which has antialdosterone activity. Hyperkalemia may occur in susceptible patients and with certain medications. See drospirenone below.

Price
  • No generic
  • 28 tablets - $$$$
Duavee®

conjugated estrogens + bazedoxifene
Tablet
Conjugated estrogens : Bazedoxifene
  • 0.45 mg : 20 mg
Menopausal vasomotor symptoms
  • Dosing: 1 tablet once daily
Prevention of postmenopausal osteoporosis
  • Dosing: 1 tablet once daily
Other
  • May take without regard to food. Swallow tablets whole.
  • Bazedoxifene is a SERM. Bazedoxifene helps to prevent endometrial hyperplasia, therefore women with a uterus do not need to take a progestin with Duavee. See for more.
  • See Duavee below for contraindications, precautions, side effects, and drug interactions

Price
  • No generic
  • 30 tablets - $$$
Femhrt®
Fyavolv®
Jevantique®
Jevantique Lo®
Jinteli®

norethindrone + ethinyl estradiol
Tablet
  • Norethindrone : EE
    • 0.5 mg : 2.5 mcg
    • 1 mg : 5 mcg
Menopausal vasomotor symptoms
  • Dosing: 1 tablet once daily
Prevention of postmenopausal osteoporosis
  • Dosing: 1 tablet once daily
Other
  • See estrogens below for side effects, contraindications, precautions, and drug interactions
  • See progestins below for side effects, contraindications, precautions, and drug interactions

Price
  • Generic available
  • 28 tablets - $-$$
Premphase®

conjugated estrogens + medroxyprogesterone
Tablet
  • 14 maroon tablets: 0.625 mg of conjugated estrogens
  • 14 light-blue tablets: 0.625 mg of conjugated estrogens + 5 mg medroxyprogesterone
Menopausal vasomotor symptoms
  • Dosing: 1 tablet once daily
Menopausal vulvar and vaginal atrophy
  • Dosing: 1 tablet once daily
Prevention of postmenopausal osteoporosis
  • Dosing: 1 tablet once daily
Other
  • See estrogens below for side effects, contraindications, precautions, and drug interactions
  • See progestins below for side effects, contraindications, precautions, and drug interactions

Price
  • No generic
  • 28 tablets - $$$-$$$$
Prempro®

conjugated estrogens + medroxyprogesterone
Tablet
  • Conjugated estrogens : Medroxyprogesterone
    • 0.3 mg : 1.5 mg
    • 0.45 mg : 1.5 mg
    • 0.625 mg : 2.5 mg
    • 0.625 mg : 5 mg
Menopausal vasomotor symptoms
  • Dosing: 1 tablet once daily
  • Titrate to desired effect. Use lowest effective dose.
Menopausal vulvar and vaginal atrophy
  • Dosing: 1 tablet once daily
  • Titrate to desired effect. Use lowest effective dose.
Prevention of postmenopausal osteoporosis
  • Dosing: 1 tablet once daily
Other
  • See estrogens below for side effects, contraindications, precautions, and drug interactions
  • See progestins below for side effects, contraindications, precautions, and drug interactions

Price
  • No generic
  • 28 tablets - $$$-$$$$

Drug Dosage forms Dosing Other / Price
Climara pro®

estradiol + levonorgestrel
Patch
  • Each patch delivers 0.045 mg/day of estradiol and 0.015 mg/day of levonorgestrel
  • Comes in carton of 4 patches
Menopausal vasomotor symptoms
  • Dosing: one patch once weekly
Prevention of postmenopausal osteoporosis
  • Dosing: one patch once weekly
Other
  • Apply to lower abdomen or the upper quadrant of the buttocks. Avoid waistline or areas where patch may be rubbed.
  • Rotate application site
  • Do not expose patch to sun for prolonged periods
  • See estrogens below for side effects, contraindications, precautions, and drug interactions
  • See progestins below for side effects, contraindications, precautions, and drug interactions

Price
  • No generic
  • 4 patches - $$$
Combipatch®

estradiol + norethindrone
Patch
  • Estradiol : Norethindrone
    • 0.05 mg/0.14 mg
    • 0.05 mg/0.25 mg
    • Strengths reflect mg/day delivered
    • Comes in carton of 8 patches
Menopausal vasomotor symptoms
  • Dosing: one patch twice weekly
  • Titrate to desired effect. Use lowest effective dose.
Menopausal vulvar and vaginal atrophy
  • Dosing: one patch twice weekly
  • Titrate to desired effect. Use lowest effective dose.
Hypogonadism, female castration, primary ovarian failure
  • Dosing: one patch twice weekly
  • Titrate to desired effect. Use lowest effective dose.
Other
  • Apply to lower abdomen. Avoid waistline or areas where patch may be rubbed.
  • Rotate application site
  • Do not expose patch to sun for prolonged periods
  • See estrogens below for side effects, contraindications, precautions, and drug interactions
  • See progestins below for side effects, contraindications, precautions, and drug interactions

Price
  • No generic
  • 8 patches - $$$

Drug Dosage forms Dosing Other / Price
Premarin® injection

conjugated estrogens
Vial
  • 25 mg
Abnormal uterine bleeding
  • Dosing: 25 mg intravenously every 4 - 6 hours for 24 hours [3]
  • May also be given intramuscularly, although IV is preferred.
  • Premarin injection may cause significant nausea. Administer with anti nausea medication.
  • See abnormal uterine bleeding for more
Other
  • Premarin injection is for short-term use to stop significant abnormal uterine bleeding

Price
  • No generic
  • 1 vial - ?
Depo-estradiol® injection

estradiol cypionate
Vial
  • 5 mg/ml
  • Comes in 5 ml vial
Menopausal vasomotor symptoms
  • Dosing: 1 - 5 mg intramuscularly every 3 - 4 weeks
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Menopausal vulvar and vaginal atrophy
  • Dosing: 1 - 5 mg intramuscularly every 3 - 4 weeks
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Hypogonadism
  • Dosing: 1.5 - 2 mg intramuscularly once monthly
  • Titrate to desired effect. Use lowest effective dose.
Other
  • Store at room temperature
  • Storage at low temperatures may result in the separation of some crystalline material which redissolves readily on warming

Price
  • No generic
  • 1 vial - $$
Delestrogen® injection

estradiol valerate
Vial
  • 10 mg/ml
  • 20 mg/ml
  • 40 mg/ml
  • Comes in 5 ml vials
Menopausal vasomotor symptoms
  • Dosing: 10 - 20 mg intramuscularly every 4 weeks
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Menopausal vulvar and vaginal atrophy
  • Dosing: 10 - 20 mg intramuscularly every 4 weeks
  • Titrate to desired effect. Use lowest effective dose.
  • Reevaluate need for therapy periodically
Hypogonadism
  • Dosing: 10 - 20 mg intramuscularly every 4 weeks
  • Titrate to desired effect. Use lowest effective dose.
Palliative treatment of advanced prostate cancer
  • Dosing: 30 mg intramuscularly every 1 - 2 weeks
Other
  • Inject in upper, outer quadrant of gluteus
  • Store at room temperature
  • Storage at low temperatures may result in the separation of some crystalline material which redissolves readily on warming

Price
  • Generic available
  • 1 vial - $$-$$$$

ESTROGEN SIDE EFFECTS
NOTE: information is from the Premarin PI. Information is for the 0.625 mg/day dose in women who had a uterus. Only side effects that occurred at an incidence ≥ 2% more than placebo are listed. P = % of patients on placebo who experienced side effect.

  • Vaginal hemorrhage - 13%, P - 0%
  • Abdominal pain - 11%, P - 6%
  • Breast pain - 11%, P - 8%
  • Flatulence - 6%, P - 2%
  • Endometrial hyperplasia - 5%, P - 0%
  • Vaginitis - 5%, P - 0%
  • Weakness - 5%, P - 1%
  • Back pain - 5%, P - 1%
  • White or yellow vaginal discharge - 5%, P - 2%
  • Yeast infection - 4%, P - 2%
  • Metrorrhagia (menstrual bleeding at irregular intervals) - 3%, P - 0%
  • Uterine spasm - 3%, P - 1%
  • Pelvic pain - 3%, P - 1%
  • Leg cramps - 3%, P - 1%
  • Itching - 3%, P - 1%
  • Dysmenorrhea (painful menses) - 3%, P - 1%
  • Cervix disorder - 2%, P - 0%
  • Application site reactions (patches) - may occur with patches
ESTROGEN CONTRAINDICATIONS
  • Estrogens are contraindicated in the following conditions:
    • Undiagnosed abnormal genital bleeding
    • Known, suspected, or history of breast cancer
    • Known or suspected estrogen-dependent neoplasia
    • Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history of these conditions (See hormone therapy during anticoagulation for VTE for more on this topic)
    • Active or recent arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
    • Know hypersensitivity
    • Known liver impairment or disease
    • Known protein C, protein S, or antithrombin deficiency, or other known thrombophilic disorders
    • Known or suspected pregnancy
ESTROGEN PRECAUTIONS
Women's Health Initiative (WHI) study
  • The WHI study was a large (over 27,000 subjects), randomized controlled trial that evaluated the long-term risks of hormone replacement therapy in postmenopausal women. The study had two arms. In one arm, women with a uterus were randomized to Prempro® or placebo. In the other arm, women who had no uterus were randomized to Premarin® or placebo.
  • The study measured a number of outcomes, and they are presented in our WHI study results tables

Estrogen precautions
  • Women with a uterus - estrogen therapy increases the risk of endometrial hyperplasia. Progestins reduce the risk. In general, women with a uterus who are taking estrogens should receive a progestin either daily in a continuous regimen or for 10 days out of the cycle in cyclical regimens. Women without a uterus (s/p hysterectomy) do not need a progestin.
  • Endometrial cancer - unopposed estrogen therapy increases the risk of endometrial cancer. Adding a progestin may help reduce the risk.
  • Stroke - in the WHI study, estrogen therapy increased the risk of stroke
  • Deep vein thrombosis (DVT) - in the WHI study, estrogen therapy increased the risk of deep vein thrombosis (DVT)
  • Gallbladder disease - estrogen therapy may increase the risk of gallbladder disease
  • Surgery and immobilization - because of the increased risk of venous thromboembolism, estrogens should be discontinued at least 4 - 6 weeks before surgery that is associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
  • Hypothyroidism - estrogens increase levels of thyroid-binding globulin. Women with normal thyroid function can compensate by making more thyroid hormone. Women with hypothyroidism may require an increase in levothyroxine dosage.
  • Retinal vascular thrombosis - has been reported in women taking estrogens. Discontinue medication if sudden visual changes occur.
  • Plasma lipids - estrogens may raise triglyceride and HDL levels while decreasing LDL levels
  • Liver disease - estrogen levels may be increased. Estrogens may exacerbate cholestatic jaundice in susceptible women.
  • Fluid retention - estrogens may cause fluid retention. Use caution in susceptible patients (e.g. kidney failure, heart failure).
  • Hypocalcemia - estrogens may worsen hypocalcemia
  • Elevated blood pressure - estrogens may raise blood pressure in some patients
  • Endometriosis - estrogens may exacerbate endometriosis. For women with residual endometriosis s/p hysterectomy, consider addition of a progestin.
  • Hereditary angioedema - estrogens may exacerbate hereditary angioedema
  • Exacerbation of other conditions - estrogens may exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas
  • Platelets and clotting factors - estrogens may increase levels and activity of platelets and clotting factors
  • Binding proteins - estrogens may increase levels of binding proteins (e.g. corticosteroid binding globulin, sex hormone-binding globulin). Other plasma proteins may also be increased (e.g. angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin)
  • Photosensitivity - estrogens may cause photosensitivity. Limit sun exposure and/or wear sunscreen to help prevent reactions.

Estrogen + progestin therapy
  • Pulmonary embolism (PE) - in the WHI study, estrogen + progestin therapy increased the risk of pulmonary embolism
  • Myocardial infarction - in the WHI study, women taking estrogen + progestin therapy had a borderline nonsignificant increase in risk of myocardial infarction
  • Dementia - in the WHI study, estrogen + progestin therapy increased the risk of developing probable dementia in women ≥ 65 years old
  • Invasive breast cancer - in the WHI study, estrogen + progestin therapy increased the risk of developing invasive breast cancer
  • Ovarian cancer - observational studies have found an increased risk of ovarian cancer in women using HRT. In the WHI study, women in the estrogen/progestin arm had a higher incidence of ovarian cancer when compared to placebo (4.2 versus 2.7 cases per 10,000 women-years). The difference was not statistically significant.

ESTROGEN DRUG INTERACTIONS
PROGESTIN SIDE EFFECTS
NOTE: the incidence of side effects from progesterone and progestins is not well-defined. Information below is from the Provera PI.

  • Genitourinary system
    • Abnormal uterine bleeding (irregular, increase, decrease), change in menstrual flow, breakthrough bleeding, spotting, amenorrhea, changes in cervical erosion and cervical secretions
  • Breasts
    • Breast tenderness, mastodynia or galactorrhea has been reported
  • Cardiovascular
    • Thromboembolic disorders including thrombophlebitis and pulmonary embolism have been reported
  • Gastrointestinal
    • Nausea, cholestatic jaundice
  • Skin
    • Sensitivity reactions consisting of urticaria, pruritus, edema and generalized rash have occurred. Acne, alopecia and hirsutism have been reported.
  • Eyes
    • Neuro-ocular lesions, for example, retinal thrombosis, and optic neuritis
  • Central nervous system
    • Mental depression, insomnia, somnolence, dizziness, headache, nervousness
  • Miscellaneous
    • Hypersensitivity reactions (for example, anaphylaxis and anaphylactoid reactions, angioedema), rash (allergic) with and without pruritus, change in weight (increase or decrease), pyrexia, edema/fluid retention, fatigue, decreased glucose tolerance.
PROGESTIN CONTRAINDICATIONS
  • Progestins are contraindicated in the following conditions:
    • PEANUT ALLERGY (Prometrium®) - Prometrium capsules contain peanut oil
    • Undiagnosed abnormal genital bleeding
    • Known, suspected, or history of breast cancer
    • Known or suspected estrogen- or progesterone-dependent neoplasia
    • Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history of these conditions (See hormone therapy during anticoagulation for VTE for more on this topic)
    • Active or recent arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
    • Know hypersensitivity
    • Known liver impairment or disease
    • Known or suspected pregnancy
PROGESTIN PRECAUTIONS
Women's Health Initiative (WHI) study
  • The WHI study was a large (over 27,000 subjects), randomized controlled trial that evaluated the long-term risks of hormone replacement therapy in postmenopausal women. The study had two arms. In one arm, women with a uterus were randomized to Prempro® or placebo. In the other arm, women who had no uterus were randomized to Premarin® or placebo.
  • The study measured a number of outcomes, and they are presented in our WHI study results tables

Progestin precautions
  • Women with a uterus - estrogen therapy increases the risk of endometrial hyperplasia. Progestins reduce the risk. In general, women with a uterus who are taking estrogens should receive a progestin either daily in a continuous regimen or for 10 days out of the cycle in cyclical regimens. Women without a uterus (s/p hysterectomy) do not need a progestin.
  • Endometrial cancer - unopposed estrogen therapy increases the risk of endometrial cancer. Adding a progestin may help reduce the risk.
  • Stroke - in the WHI study, women taking Prempro (conjugated estrogens + medroxyprogesterone) had an increased risk of stroke when compared to placebo. The risk of stroke was also increased in women who took conjugated estrogens only. The strength of association between stroke and progesterone is unknown.
  • Deep vein thrombosis (DVT) - in the WHI study, women taking Prempro (conjugated estrogens + medroxyprogesterone) had an increased risk of DVT when compared to placebo. The risk of DVT was also increased in women who took conjugated estrogens only. The strength of association between DVT and progesterone is unknown.
  • Surgery and immobilization - because of the increased risk of venous thromboembolism, estrogen + progestin therapy should be discontinued at least 4 - 6 weeks before surgery that is associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
  • Pulmonary embolism (PE) - in the WHI study, women taking Prempro (conjugated estrogens + medroxyprogesterone) had an increased risk of PE when compared to placebo. The strength of association between PE and progesterone is unknown.
  • Dementia - in the WHI study, women ≥ 65 years old taking Prempro (conjugated estrogens + medroxyprogesterone) had an increased risk of probable dementia when compared to placebo. The strength of association between dementia and progesterone is unknown.
  • Invasive breast cancer - in the WHI study, women taking Prempro (conjugated estrogens + medroxyprogesterone) had an increased risk of invasive breast cancer when compared to placebo. The risk of invasive breast cancer was not increased in women who took conjugated estrogens only. The strength of association between invasive breast cancer and progesterone is unknown.
  • Heart attack - in the WHI study, women taking Prempro (conjugated estrogens + medroxyprogesterone) had a borderline nonsignificant increased risk of heart attack when compared to placebo. The strength of association between heart attack risk and progesterone is unknown.
  • Endometriosis - estrogens may exacerbate endometriosis. For women with residual endometriosis s/p hysterectomy, consider addition of a progestin.
  • Hypothyroidism - estrogen + progestin therapy may increase levels of thyroid-binding globulin. Women with normal thyroid function can compensate by making more thyroid hormone. Women with hypothyroidism may require an increase in levothyroxine dosage.
  • Elevated blood pressure - progestins may raise blood pressure in some patients
  • Plasma lipids - progestins may raise triglyceride and HDL levels while decreasing LDL levels
  • Liver disease - progestin levels may be increased
  • Fluid retention - progestins may cause fluid retention. Use caution in susceptible patients (e.g. kidney failure, heart failure).
  • Exacerbation of other conditions - estrogen + progestin therapy may exacerbate asthma, diabetes mellitus, epilepsy, migraine, porphyria, systemic lupus erythematosus, and hepatic hemangiomas
  • Platelets and clotting factors - estrogen + progestin therapy may increase levels and activity of platelets and clotting factors
  • Binding proteins - estrogen + progestin therapy may increase levels of binding proteins (e.g. corticosteroid binding globulin, sex hormone-binding globulin). Other plasma proteins may be increased (e.g. angiotensinogen/renin substrate, alpha-1-antitrypsin, ceruloplasmin)

Progestin + estrogen therapy
  • Pulmonary embolism (PE) - in the WHI study, estrogen + progestin therapy increased the risk of pulmonary embolism
  • Myocardial infarction - in the WHI study, women taking estrogen + progestin therapy had a borderline nonsignificant increase in risk of myocardial infarction
  • Dementia - in the WHI study, estrogen + progestin therapy increased the risk of developing probable dementia in women ≥ 65 years old
  • Invasive breast cancer - in the WHI study, estrogen + progestin therapy increased the risk of developing invasive breast cancer
  • Ovarian cancer - observational studies have found an increased risk of ovarian cancer in women using HRT. In the WHI study, women in the estrogen/progestin arm had a higher incidence of ovarian cancer when compared to placebo (4.2 versus 2.7 cases per 10,000 women-years). The difference was not statistically significant.
PROGESTIN DRUG INTERACTIONS
  • CYP3A4 inducers and inhibitors - progestins are metabolized by CYP3A4. CYP3A4 inducers may decrease progestin levels and CYP3A4 inhibitors may increase progestin levels.
DROSPIRENONE
Angeliq contains the progestin drospirenone. Drospirenone has antialdosterone properties which means it may contribute to hyperkalemia when taken by itself and/or when combined with other potassium-raising medications.

  • Contraindications - Angeliq is contraindicated in women with kidney or liver impairment. It is also contraindicated in women with adrenal insufficiency.
  • Drug interactions
    • CYP3A4 strong inhibitors - Use caution and consider monitoring potassium levels when taking Angeliq with strong CYP3A4 inhibitors
    • Drugs that may raise potassium - Angeliq may raise potassium levels when taken with other drugs that raise potassium such as ACE inhibitors, angiotensin receptor blockers, aldosterone antagonists, and NSAIDs. In studies involving postmenopausal women who were taking ACE inhibitors or ARBs, drospirenone 3 mg once daily for a month raised potassium levels an average of 0.11 mEq/L while placebo-treated patients saw an average increase of 0.08 mEq/L.
OSPHENA® PRESCRIBING INFORMATION
Mechanism of action
  • Ospemifene is a selective estrogen receptor modulator (SERM). SERMs act as estrogen receptor agonists (stimulate) in some tissues and as estrogen receptor antagonists (block) in other tissues. See for more.

    • Ospemifene has the following activities:
      • Endometrium - neutral to partial agonist
      • Vagina - agonist
      • Breast - antagonist
      • Bone - osteoclast formation - neutral; bone resorption - antagonist; bone formation - agonist [2]

Contraindications
  • Undiagnosed abnormal genital bleeding
  • Known or suspected estrogen-dependent neoplasia
  • Active deep vein thrombosis (DVT), pulmonary embolism (PE), or a history of these conditions
  • Active or recent arterial thromboembolic disease (for example, stroke and MI), or a history of these conditions
  • Know hypersensitivity
  • Known or suspected pregnancy

Precautions
  • Stroke - in the WHI study, estrogen therapy increased the risk for stroke. In the clinical trials for ospemifene (duration of treatment up to 15 months), the incidence rates of thromboembolic and hemorrhagic stroke were 0.72 and 1.45 per thousand women, respectively in the ospemifene group and 1.04 and 0 per thousand women in the placebo group.
  • Venous thromboembolism (VTE) - in the WHI study, estrogen therapy increased the risk for VTE. In ospemifene clinical trials, the incidence of DVT was 1.45 per thousand women in the ospemifene group and 1.04 per thousand women in the placebo group.
  • Endometrial thickening and endometrial cancer - ospemifene is a partial agonist in endometrial tissue. It causes endometrial thickening in some women (in trials, ≥ 5 mm thickening was seen in 60.1 per thousand women treated with ospemifene vs. 21.2 per thousand women treated with placebo). Endometrial thickening may lead to endometrial hyperplasia and cancer. The addition of a progestin to ospemifene therapy may decrease the risk of endometrial hyperplasia and cancer.
  • Surgery and immobilization - because of the increased risk of venous thromboembolism, ospemifene should be discontinued at least 4 - 6 weeks before surgery that is associated with an increased risk of thromboembolism, or during periods of prolonged immobilization.
  • Uterine polyps - in trials, uterine polyps occurred at an incidence of 5.9 per thousand women in the ospemifene group vs. 1.8 per thousand women in the placebo group
  • Breast cancer - ospemifene has not been studied adequately in women with breast cancer and therefore should not be used
  • Kidney disease - no dose adjustment necessary
  • Liver disease
    • Mild to moderate (Child-Pugh A/B) - no dose adjustment necessary
    • Severe (Child-Pugh C) - has not been studied. DO NOT USE.

Side effects
NOTE: P = % of patients taking placebo who experienced side effect
  • Hot flush - 7.5%, P - 2.6%
  • Vaginal discharge - 3.8%, P - 0.3%
  • Muscle spasm - 3.2%, P - 0.9%
  • Excessive sweating - 1.6%, P - 0.6%
  • Genital discharge - 1.3%, P - 0.1%

Drug interactions
  • Ospemifene is primarily metabolized by CYP3A4 and CYP2C9. CYP2C19 also contributes to its metabolism. Drugs that inhibit both CYP3A4 and CYP2C9 may increase exposure to ospemifene.
  • Other estrogens and SERMs - DO NOT COMBINE. Ospemifene should not be used with estrogens or other SERMs
  • Fluconazole (Diflucan®) - DO NOT COMBINE. Fluconazole is a moderate CYP3A / strong CYP2C9 / moderate CYP2C19 inhibitor. Exposure to ospemifene is increased.
  • Rifampin - rifampin is a strong CYP3A4 / moderate CYP2C9 / moderate CYP2C19 inducer. Exposure to ospemifene is decreased.
  • Ketoconazole - ketoconazole is a strong CYP3A4 inhibitor. Exposure to ospemifene is increased by 1.4-fold. Use caution in chronic dosing.
  • Highly protein-bound drugs - ospemifene is 99% bound to serum proteins. It may affect the protein binding of other drugs.
DUAVEE® PRESCRIBING INFORMATION
Mechanism of action
  • Duavee contains bazedoxifene and conjugated estrogens
  • Bazedoxifene is a selective estrogen receptor modulator (SERM). SERMs act as estrogen receptor agonists (stimulate) in some tissues and as estrogen receptor antagonists (block) in other tissues. See for more.

    • Bazedoxifene has the following activities:
      • Endometrium - neutral to antagonist
      • Vagina - unknown
      • Breast - antagonist
      • Bone - agonist [2]

Contraindications
Precautions
  • Bazedoxifene helps to prevent endometrial hyperplasia, therefore women with a uterus do not need to take a progestin with Duavee
  • Precautions with Duavee are the same as those with conjugated estrogens (see estrogen precautions above)

Side effects
NOTE: P = % of patients taking placebo who experienced side effect. Only side effects that occurred at an incidence ≥ 2% more than placebo are listed
  • Muscle spasm - 9%, P - 6%
  • Nausea - 8%, P - 5%
  • Diarrhea - 8%, P - 5%
  • Upper abdominal pain - 7%, P - 5%
  • Dizziness - 5%, P - 3%

Drug interactions
  • CYP3A4 inducers and inhibitors - estrogens are partially metabolized by CYP3A4. CYP3A4 inducers may decrease estrogen levels and CYP3A4 inhibitors may increase estrogen levels.
  • Uridine Diphosphate Glucuronosyltransferase (UGT) - bazedoxifene undergoes metabolism by the UGT enzyme in the intestinal tract and liver. Metabolism of bazedoxifene may be increased by UGT inducers (e.g. rifampin, phenobarbital, carbamazepine, phenytoin). A reduction in bazedoxifene exposure may lead to endometrial hyperplasia.
INTRAROSA® PRESCRIBING INFORMATION
Contraindications
  • Undiagnosed abnormal genital bleeding - Any postmenopausal woman with undiagnosed, persistent or recurring genital bleeding should be evaluated to determine the cause of the bleeding before consideration of treatment with Intrarosa

Precautions
  • Breast cancer - estrogen is a metabolite of prasterone. Estrogen therapy is contraindicated in women with known or suspected breast cancer.
  • Kidney disease - has not been studied
  • Liver disease - has not been studied

Side effects
  • Vaginal discharge - vaginal discharge is the most frequently reported side effect of Intrarosa occurring in up to 14% of treated women
  • Abnormal PAP smear - in a 52-week trial (n=521) without a control group, 2.1% of women had an abnormal PAP smear

Drug interactions
  • None known