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OCP HRT
SHELAGH LARSON, WHNP, NCMP
UNIVERSITY OF NORTH TEXAS HEALTH SCIENCE CENTER
HISTORY OF THE PILL • 1873:THE U.S. CONGRESS PASSES THE COMSTOCK LAW, WHICH PROHIBITS THE DISTRIBUTION OF OBSCENE MATERIAL THROUGH THE U.S.
MAIL OR ACROSS STATE LINES. IT SPECIFICALLY IDENTIFIES CONTRACEPTIVES AS OBSCENE.
• 1912: RADICAL FEMINIST MARGARET SANGER CONCEIVES OF A "MAGIC PILL" CONTRACEPTIVE. SANGER LATER FOUNDED THE AMERICAN BIRTH CONTROL LEAGUE, WHICH EVENTUALLY BECAME THE PLANNED PARENTHOOD FEDERATION.
• 1930:ON AUGUST 15, MEETING OF THE ANGLICAN CHURCH'S BISHOPS APPROVES THE USE OF CONTRACEPTIVES. AFTER 1930, OTHER PROTESTANT DENOMINATIONS BEGIN TO ALLOW CONTRACEPTION. POPE PIUS XI REAFFIRMS THE CATHOLIC CHURCH'S CONSTANT TEACHING AGAINST CONTRACEPTION AND ABORTION
• 1951:SANGER OBTAINS A PLANNED PARENTHOOD GRANT FOR DR. GREGORY PINCUS, A BIOLOGIST, TO RESEARCH HORMONAL CONTRACEPTIVES
• 1954 PINCUS AND DR. JOHN ROCK, A CATHOLIC OB-GYN BEGIN HUMAN TRIALS OF THE PILL. TO BYPASS MASSACHUSETTS'S ANTI-BIRTH CONTROL LAWS, THEY CLAIM THE STUDY IS ABOUT INFERTILITY. FIFTY FEMALE INFERTILITY PATIENTS. 1955:THE PILL IS PROVEN TO PREVENT OVULATION IN ALL 50 WOMEN.
• 1956:LARGE-SCALE HUMAN CLINICAL TRIALS OF THE PILL BEGIN, TO GAIN APPROVAL BY (FDA). PINCUS CHOOSES PUERTO RICO AS THE LOCATION BECAUSE IT A LARGE POOL OF POOR, UNEDUCATED WOMEN WHO CAN BE EASILY MONITORED.
• 1957:THE FDA APPROVES USAGE OF THE PILL TO TREAT SEVERE MENSTRUAL DISORDERS. REQUIRES THAT ITS P.I. INCLUDE A WARNING THAT IT WILL PREVENT OVULATION.
• 1960:THE PHARMACEUTICAL COMPANY G.D. SEARLE OBTAINS FDA APPROVAL TO SELL THE PILL AS A CONTRACEPTIVE IT BECOMES THE FIRST FDA-APPROVED DRUG TO BE GIVEN TO HEALTHY PATIENTS FOR LONG-TERM USE AND FOR SOCIAL PURPOSES.
HORMONES IN OCPS ETHINYL ESTRADIOL
• THE ESTROGEN TYPICALLY CONTAINED IN ALL COMBINATION BIRTH CONTROL PILLS
• WORK BY PREVENTING THE FORMATION OF A FOLLICLE
CLASSIFIED BY ESTROGEN LEVEL:
• LOW DOSE PILLS (LEAST AMOUNT) (20 MCG)
• REGULAR DOSE PILLS CONTAIN 30–35 MCG
• HIGH DOSE PILLS HAVE ABOUT 50 MCG
PROGESTIN • THE TERM PROGESTIN IS USED FOR ANY
NATURAL OR MAN-MADE SUBSTANCE THAT HAS PROPERTIES SIMILAR TO NATURAL PROGESTERONE.
• ONE OF EIGHT KINDS OF PROGESTIN.
• INHIBIT THE LUTEINIZING HORMONE (LH) SURGE, WHICH IS REQUIRED FOR OVULATION
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ESTROGENIC EFFECTS
• ESTROGENIC ACTIVITY HAS TO DO WITH ETHINYL ESTRADIOL,
• HIGHER NUMBER OF MICROGRAMS LEAD TO MORE POTENT ESTROGENIC EFFECTS.
• HIGHER AMOUNT HELPS TO DECREASE ANDROGEN-RELATED SIDE EFFECTS.
• HOWEVER, PROGESTINS TEND TO COUNTER SOME OF THE ESTROGENIC EFFECTS
• PREVENTS THE RELEASE OF FOLLICLE-STIMULATING HORMONE (FSH) FROM THE ANTERIOR PITUITARY. WHEN KEPT LOW, A FOLLICLE IS NOT ABLE TO FORM AND OVULATION IS PREVENTED.
• LUTEINIZING HORMONE AND THUS ANDROGEN PRODUCTION FROM THE OVARY, AND ENHANCES HEPATIC PRODUCTION OF SHBG, THEREBY REDUCING FREE PLASMA TESTOSTERONE.
TYPES OF PROGESTINS
• EACH HAS A DIFFERENT ACTIVITY A/O EFFECTS IN TERMS OF: • PROGESTATIONAL • ESTROGENIC • ANDROGENIC
• THE RESULT IS DEPENDENT ON THE COMBINATION OF THE TYPE AND LEVEL OF PROGESTIN AND THE LEVEL OF ESTROGEN
PROGESTATIONAL EFFECTS
• PROGESTATIONAL EFFECTS: REFERS TO HOW THE PROGESTIN STIMULATES THE PROGESTERONE RECEPTORS (THEREBY HELPING TO PREVENT OVULATION AND TO LESSEN MENSTRUAL BLEEDING).
• A PROGESTATIONAL SELECTIVITY, IS THE DEGREE TO WHICH PROGESTATIONAL EFFECTS ARE MAXIMIZED AND ANDROGENIC EFFECTS ARE MINIMIZED.
• *TYPICALLY, THE GOAL OF A BIRTH CONTROL PILL IS TO ACHIEVE A HIGH LEVEL OF PROGESTATIONAL SELECTIVITY
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ANDROGENIC EFFECTS:
• ANDROGENIC EFFECTS: THE LIKELIHOOD THAT THE PROGESTIN MAY CAUSE UNPLEASANT SIDE EFFECTS.
• HIGHER ANDROGENIC ACTIVITY: INCREASES THE CHANCES OF ANDROGEN-RELATED SIDE EFFECTS (MAINLY, ACNE AND HIRSUTISM)
• LESS ANDROGENIC ACTIVITY: LITTLE - NO EFFECT ON CARBOHYDRATE METABOLISM, WHICH IS HOW THE BODY BREAKDOWNS AND SYNTHESIZES SIMPLE SUGARS INTO SMALLER UNITS THAT CAN THEN BE USED BY THE BODY FOR ENERGY.
CLASSIFICATION OF PROGESTINS:
THE ESTRANE FAMILY FIRST GENERATION PROGESTINS (TYPICALLY)
CONSIST OF NORETHINDRONE AND OTHER PROGESTINS THAT METABOLIZE TO NORETHINDRONE.
INCLUDES: NORETHINDRONE ACETATE
ETHYNODIOL DIACETATE
THE GONANE FAMILY SECOND GENERATION WHICH HAVE VARYING DEGREES OF ANDROGENIC AND ESTROGENIC ACTIVITIES.
INCLUDES: LEVONORGESTREL NORGESTREL.
THIRD GENERATION HAVE THE LEAST ANDROGENIC EFFECTS
INCLUDES: DESOGESTREL NORGESTIMATE.
3RD GENERATION MAY CARRY A HIGHER RISK OF BLOOD CLOTS
DROSPIRENONE •THE NEWEST (4TH) GENERATION.
IT DIFFERS BECAUSE IT IS DERIVED FROM 17A-SPIROLACTONE, NOT FROM THE 19-NORTESTOSTERONE DERIVATIVES.
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NORETHINDRONE
• FIRST-GENERATION PROGESTIN
• LOW PROGESTATIONAL
• SLIGHT ESTROGENIC ACTIVITY
• TENDS TO BE LESS ANDROGENIC THAN THE SECOND-GENERATION PROGESTINS (LEVONORGESTREL AND NORGESTREL), BUT MORE ANDROGENIC THAN NEWER PROGESTINS, LIKE DESOGESTREL.
• IMPROVES LIPID PROFILES BY RAISING HDL AND LOWERING LDL.
• AVAILABLE IN MONOPHASIC, BIPHASIC AND TRIPHASIC , FORMULATIONS.
Ortho-Novum 7/7/7
ETHYNODIOL DIACETATE
• A FIRST-GENERATION PROGESTIN
• MEDIUM PROGESTATIONAL ACTIVITY.
• IT HAS MINOR ESTROGENIC EFFECTS AND LITTLE ANDROGENIC ACTIVITY.
• A DERIVATIVE OF NORETHINDRONE, SO IT IS EASILY CONVERTED TO NORETHINDRONE WITHIN THE BODY.
• TEND TO BE ASSOCIATED WITH ^ EARLY OR MID-CYCLE BREAKTHROUGH BLEEDING AND SPOTTING
• HOWEVER, HIGHER ESTROGEN DOSAGES CAN COUNTERACT THE LIKELIHOOD OF BREAKTHROUGH BLEEDING, SO PILL BRANDS THAT CONTAIN HIGHER LEVELS OF ESTROGEN CAN ALLEVIATE THIS SIDE EFFECT.
NORETHINDRONE ACETATE
• FIRST-GENERATION PROGESTIN
• LOW PROGESTATIONAL ACTIVITY
• SLIGHT ESTROGENIC AFFECTS.
• LESS ANDROGENIC THAN THE SECOND-GENERATION PROGESTINS, BUT MORE ANDROGENIC THAN NEWER PROGESTINS, LIKE DESOGESTREL.
• “ESTROSTEP” WAS DESIGNED TO MORE CLOSELY MIMIC A WOMAN'S NATURAL MENSTRUAL CYCLE BY PROVIDING INCREASING LEVELS OF ESTROGEN WITH A CONSTANT PROGESTIN DOSE.
• IT IS THE ONLY TRIPHASIC BRAND WITH THIS PROGESTIN.
• HELPFUL FOR WOMEN WHO EXPERIENCE MINOR ESTROGEN-RELATED SIDE EFFECTS SUCH AS NAUSEA, MIGRAINES OR FLUID RETENTION WITH OTHER PILLS
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NORGESTREL
• A SECOND-GENERATION PROGESTIN
• A MIXTURE OF AN INACTIVE AND ACTIVE ISOMER -- DEXTRO-NORGESTREL (INACTIVE) AND LEVONORGESTREL (BIOLOGICALLY ACTIVE).
• HIGH PROGESTATIONAL
• STRONG ANTI-ESTROGEN EFFECTS
• HIGH IN ANDROGENIC ACTIVITY.
• IT MAY CAUSE LDL CHOLESTEROL TO BE INCREASED WHILE ALLOWING FOR HDL CHOLESTEROL TO BE LOWERED.
LEVONORGESTREL
• A SECOND-GENERATION PROGESTIN
• THE MOST WIDELY PRESCRIBED CONTRACEPTIVE PROGESTIN WORLDWIDE.
• HIGH PROGESTATIONAL AND ANDROGENIC EFFECTS.
• LEVONORGESTREL NEGATIVELY AFFECTS SERUM LIPOPROTEINS.
• SEVERAL LOW-DOSE ESTROGEN BRANDS CONTAINING THIS PROGESTIN ARE AVAILABLE.
• APPROVED FOR EMERGENCY CONTRACEPTION (SUCH AS PLAN B ONE-STEP AND NEXT CHOICE).
• THE FDA STATED ALL OCPS WITH THIS PROGESTIN ARE SAFE AND EFFECTIVE FOR EMERGENCY CONTRACEPTION UNDER THE YUZPE METHOD.
• THE FDA HAS ALSO APPROVED THREE EXTENDED CYCLE PILL BRANDS THAT USE THIS PROGESTIN -- SEASONALE, SEASONIQUE, AND LYBREL.
Levonorgestrel
NORGESTIMATE
• A THIRD-GENERATION PROGESTIN
• HAS HIGH PROGESTATIONAL ACTIVITY WHILE SHOWING SLIGHT ESTROGENIC EFFECTS
• TENDS TO BE LESS ANDROGENIC.
• MINIMAL EFFECT ON SERUM LIPOPROTEINS AND CARBOHYDRATE METABOLISM.
• THE LOW ANDROGENIC EFFECTS SUCCESSFUL TREATMENT OF ACNE.
• ARE THE ONLY ONE FDA APPROVED TO HELP REDUCE ACNE.
• ORTHO TRI-CYCLEN LO IS MID-LEVEL DOSE OF ESTROGEN.
• MAY BE HELPFUL IN LOWERING SIDE EFFECTS SUCH AS NAUSEA AND VOMITING WHILE NOT CAUSING AN INCREASED INCIDENCE OF SPOTTING (TYPICALLY ASSOCIATED WITH LOW-ESTROGEN PILLS).
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DESOGESTREL
• A THIRD-GENERATION PROGESTIN
• WITH HIGH PROGESTATIONAL SELECTIVITY, MINIMIZING ANDROGENIC EFFECTS AND ESTROGENIC ACTIVITY.
• LESS NEGATIVE IMPACT ON METABOLISM, WEIGHT GAIN, ACNE, AND OTHER SIDE EFFECTS TYPICAL OF OLDER PROGESTINS.
• IT SHOWS POSITIVE EFFECTS ON LIPOPROTEINS AS SEEN BY A SLIGHT RISE OF HDL CHOLESTEROL.
• A POSSIBLY HIGHER RISK OF NON-FATAL VENOUS THROMBOSIS WITH DESOGESTREL PILLS VERSUS THOSE WITH LEVONORGESTREL.
• MIRCETTE (A LOW-DOSE ESTROGEN/DESOGESTREL PILL) PROVIDES A SHORTER PLACEBO INTERVAL, WHICH MAY BE HELPFUL FOR WOMEN WHO HAVE MIGRAINES, DYSMENORRHEA, OR OTHER NEGATIVE ISSUES DURING THAT WEEK.
• A LOW ESTROGEN/VARYING DESOGESTREL TRIPHASIC PILL, CYCLESSA, IS ALSO AVAILABLE
DROSPIRENONE
• IS THE ONLY PROGESTIN DERIVED FROM 17A-SPIROLACTONEIS.
• IT HELPS SUPPRESS THE SECRETION OF THE HORMONES THAT REGULATE THE BODY'S WATER AND ELECTROLYTES.
• LOW ANDROGENIC ACTIVITY.
• WITH ESTROGEN, LESSEN SYMPTOMS ASSOCIATED WITH MILD PMS (INCREASED APPETITE, NEGATIVE MOOD, AND WATER RETENTION).
• MAY CAUSE HIGHER POTASSIUM LEVELS, SO WOMEN WITH KIDNEY, LIVER, OR ADRENAL DISEASE SHOULD NOT USE IT.
• 24 DAYS OF ACTIVE PILLS AND 4 DAYS OF PLACEBO PILLS MAY CAUSE FEWER HORMONE FLUCTUATIONS THAN TYPICAL PILL PACKS.
• “YAZ” FDA APPROVED TO HELP TREAT PREMENSTRUAL DYSPHORIC DISORDER AND TREAT MODERATE ACNE IN FEMALES AGED 14 YEARS AND UP.
• NOT FROM THE 19-NORTESTOSTERONE DERIVATIVES.
• INHIBITION OF OVARIAN AND ADRENAL ANDROGEN PRODUCTION, BLOCKAGE OF DHT BINDING TO SKIN ANDROGEN RECEPTORS, ELEVATION OF SHBG LEVELS, INCREASED TESTOSTERONE CLEARANCE FROM THE BODY, AND DECREASED 5Α-REDUCTASE ACTIVITY.
CHOOSING A BIRTH CONTROL PILL BY MINIMIZING ITS SIDE EFFECTS
Side Effect (Problem) Progestin/Estrogen/Androgenic Effects
Use These Pill Brands (to minimize side effect)
Absent period or too light menstrual flow
higher estrogen, lower progestin potency
Brevicon, Modicon, Necon 1/35, Necon 1/50, Norinyl 1/35, Norinyl 1/50, Ortho-Cyclen, Ortho-Novum 1-35,Ortho-Novum 1/50, Ovcon 35
Acne
higher estrogen, lower androgen potency
Demulen 1/50, Brevicon, Mircette, Modicon, Necon, Othro-Cyclen, Ortho-TriCyclen, Yasmin
Break through bleeding (spotting)
higher estrogen, higher progestin potency, lower androgen potency
Demulen 1/50, Desogen, Ortho-Cept, Ovcon 50, Yasmin, Zovia 1/50E, Estrostep FE**
Breast soreness lower estrogen, lower progestin potency Alesse, Levlite
Depression lower estrogen, lower progestin potency Alesse, Brevicon, Levlite, Modicon, Necon 1/35, Ortho-Cyclen, Othro-TriCyclen, Ovcon 35,Tri-Levlen, Triphasil, Trivora
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CHOOSING A BIRTH CONTROL PILL BY MINIMIZING ITS SIDE EFFECTS
Side Effect (Problem) Progestin/Estrogen/Androgenic Effects
Use These Pill Brands (to minimize side effect)
Endometriosis or endometriosis prevention
lower estrogen, higher progestin potency, higher androgen potency
Demulen 1/35, Levlen, Levora, Loestrin 1.5/30, Loestrin 1/20 Fe, LoOvral, Nordette, Zovia 1/35E, (continuously, no placebo pills or only 4 days of placebo pills for prevention)
Headaches (not menstrual migraines)
lower estrogen, lower progestin potency Alesse, Brevicon, Levlite, Modicon, Necon 1/35, Ortho-Cyclen, Othro-TriCyclen, Ovcon 35 , Tri-Levlen, Triphasil, Trivora
Moodiness or irritability lower progestin potency Alesse, Levlite, Loestrin 1/20 Fe, Yasmin, (or any pill with less estrogen than currently on)
Severe menstrual cramps higher progestin potency Demulen 1/35, Demulen 1/50, Desogen, Mircette, Loestrin 1.5/30, Ortho-Cept, Yasmin, Zovia 1/35E, Zovia 1/50E
Weight gain higher progestin potency Alesse, Levlite, Loestrin 1/20 Fe, Yasmin, (or any pill with less estrogen than currently on)
ADVERSE EFFECTS ASSOCIATED WITH TYPE OF HORMONAL ACTIVITY
ESTROGENIC
BLOATING
NAUSEA/VOMITING
BREAST FULLNESS
BREAKTHROUGH BLEEDING
IRRITABILITY
HEADACHES
HYPERTENSION
PROGESTATIONAL
HEADACHES
BREAST PAIN/TENDERNESS
HYPERTENSION
ANDROGENIC
ACNE/OILY SKIN
WEIGHT GAIN
HIRSUTISM
FATIGUE
DEPRESSION
ESTROGEN DOSE RELATED ADVERSE EFFECTS
EXCESS
• NAUSEA/VOMITING
• BLOATING/EDEMA
• HYPERTENSION
• MIGRAINES
• BREAST TENDERNESS
• DECREASED LIBIDO
• WEIGHT GAIN
• HEAVY MENSTRUAL FLOW
• LEUKORRHEA
DEFICIENCY
• EARLY CYCLE SPOTTING/BTB
• AMENORRHEA
• VAGINAL DRYNESS
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PROGESTIN DOSE RELATED ADVERSE EFFECTS
EXCESS
• ACNE
• ^ APPETITE/WEIGHT GAIN
• FATIGUE
• HTN
• DEPRESSION
• HIRSUTISM
• VAGINAL YEAST INFECTION
DEFICIENCY
• LATE BREAKTHROUGH BLEEDING
• AMENORRHEA
• HEAVY MENSTRUAL FLOW
CONTRAINDICATION TO COMBINATION HORMONAL ACTIVITY
ABSOLUTE CONTRAINDICATION
RELATIVE CONTRAINDICATION • HYPERTENSION
• MIGRAINES
• DIABETES
• EPILEPSY
• OBSTRUCTIVE JAUNDICE IN PREGNANCY
• GALLBLADDER DISEASE
• SURGERY WITH PROLONGED IMMOBILIZATION
• SICKLE CELL DISEASE
• HYPERSENSITIVITY
• KNOWN/SUSPECTED PREGNANCY
• SMOKERS >35YEARS OLD > 15 CIGARETTES/DAY
• CEREBROVASCULAR OR CORONARY ARTERY DISEASE
• THROMBOEMBOLIC DISORDERS: PE, MI DVT, STROKE, THROMBOPHLEBITIS
• KNOWN/SUSPECTED BREAST CANCER
• UNDIAGNOSED AUB
• MARKED LIVER FUNCTION IMPAIRMENT
POLYCYSTIC OVARIAN SYNDROME • ONE OF THE MOST COMMON ENDOCRINOPATHIES IN REPRODUCTIVE-AGE WOMEN.
• SPECTRUM OF DISORDERS WITH ANY COMBINATION OF OLIGO/ANOVULATION, CLINICAL AND/OR BIOCHEMICAL EVIDENCE OF ANDROGEN EXCESS, OBESITY, INSULIN RESISTANCE AND POLYCYSTIC OVARIES ON ULTRASOUND.
• INHIBITION OF OVARIAN AND ADRENAL ANDROGEN PRODUCTION, BLOCKAGE OF DHT BINDING TO SKIN ANDROGEN RECEPTORS, ELEVATION OF SHBG LEVELS, INCREASED TESTOSTERONE CLEARANCE FROM THE BODY, AND DECREASED 5Α-REDUCTASE ACTIVITY.
• USE OF OCP AND SPIRONOLACTONE FOR THE TREATMENT OF HIRSUTISM, AND THE HIGHLY EFFECTIVE METFORMIN IF THERE IS OBESITY AND EVIDENCE OF INSULIN RESISTANCE.
• THESE ARE PRESCRIBED WITH EMPHASIS ON THE FACT THAT HEALTHY DIET AND REGULAR EXERCISE ARE THE BEST WAY TO TREAT PCOS SYMPTOMS AND PREVENT COMPLICATIONS OF OBESITY AND INSULIN RESISTANCE.
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PCOS TREATMENT
• ORAL CONTRACEPTIVE THERAPY IS USED TO REDUCE ANDROGEN AND LH LEVELS WITH RESULTANT IMPROVEMENT IN ACNE AND HIRSUTISM, AND THE INDUCTION OF REGULAR MENSES.
• ANTI-ANDROGENS ARE USUALLY REQUIRED FOR A SUBSTANTIAL IMPROVEMENT IN HIRSUTISM SCORE.
• INSULIN SENSITIZERS BY IMPROVING INSULIN SENSITIVITY AND DECREASING INSULIN LEVELS, WHICH ALSO HELPS TO INCREASE SHBG, DECREASE ANDROGEN LEVELS AND INDUCE OVULATION.
PCOS
• ENDOCRINOLOGIST STILL PREFER TO USE OCPS WITH LOW ANDROGENIC POTENTIAL:
• DEMULEN 1/50® (USEFUL IN OBESE PATIENTS, WHO REQUIRE HIGHER DOSES OF ESTROGEN),
• ORTHO-TRI-CYCLEN® (FDA APPROVED FOR TREATMENT OF ACNE IN WOMEN) OR
• YASMIN®, WHICH CONTAINS DROSPIRENONE (SPIRONOLACTONE-RELATED, ANTI-MINERALOCORTICOID WITH ANTI-ANDROGENIC ACTIVITY).
HORMONE THERAPY FOR
PERIMENOPAUSE & MENOPAUSE
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WHAT IS MENOPAUSE?
• A NORMAL, NATURAL EVENT, DEFINED AS THE FINAL MENSTRUAL PERIOD (FMP), CONFIRMED AFTER 1 YEAR OF NO MENSTRUAL BLEEDING
• REPRESENTS THE PERMANENT CESSATION OF MENSES RESULTING FROM LOSS OF OVARIAN FOLLICULAR FUNCTION, USUALLY DUE TO AGING
• NATURALLY (SPONTANEOUSLY) AVERAGE AGE 51.4
• PREMATURELY FROM MEDICAL INTERVENTION (BILATERAL OOPHORECTOMY,
CHEMOTHERAPY)
• AT ANY TIME FROM IMPAIRED OVARIAN FUNCTION
LIFETIME MENSTRUAL EVENTS
PREGNANCY
• AVERAGE AGE: 23
• AVERAGE OLDEST AGE: 44
• CHILDBEARING YEARS: 21
• AVERAGE MONTHS : 21
• MENARCHE AGE: 12.5
MENOPAUSAL
• AVERAGE AGE 51
• AVERAGE DEATH RATE: 81/85
• AVERAGE YEARS: 31
• PERIMENOPAUSE: 4 YEARS
• OVER 1/3 LIFE
2012 CONSENSUS STATEMENT ON HORMONE THERAPY
• AGREE THAT THE DECISION TO INITIATE HORMONE THERAPY SHOULD BE FOR THE INDICATION OF TREATMENT OF MENOPAUSE RELATED SYMPTOMS.
• HORMONE THERAPY HAS AN IMPORTANT ROLE IN MANAGING SYMPTOMS FOR WOMEN DURING THE MENOPAUSAL TRANSITION AND IN EARLY MENOPAUSE.
Fertility and Sterility® Vol. 98, No. 2, August 2012
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2012 CONSENSUS STATEMENT FOR HORMONE THERAPY: OVERVIEW
• SYSTEMIC HORMONE THERAPY IS AN ACCEPTABLE OPTION FOR RELATIVELY YOUNG (UP TO AGE 59 OR < 10 YEARS OF MENOPAUSE)
• INDIVIDUALIZATION IS KEY
• CONSIDERATION SHOULD BE GIVEN TO QUALITY-OF-LIFE PRIORITIES AND PERSONAL RISK FACTORS: AGE, TIME SINCE MENOPAUSE, AND
HER RISK OF BLOOD CLOTS, HEART DISEASE, STROKE, AND BREAST CANCER.
2012 CONSENSUS STATEMENT FOR HORMONE THERAPY: MEMBERS
• ACADEMY OF WOMEN'S HEALTH
• AMERICAN ACADEMY OF FAMILY PHYSICIANS,
• AMERICAN ACADEMY OF PHYSICIAN ASSISTANTS,
• AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE
• THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS,
• AMERICAN MEDICAL WOMEN'S ASSOCIATION,
• ASOCIACION MEXICANA PARA EL ESTUDIO DEL CLIMATERIO,
• ASSOCIATION OF REPRODUCTIVE HEALTH PROFESSIONALS
• THE ENDOCRINE SOCIETY
• NATIONAL ASSOCIATION OF NURSE PRACTITIONERS IN WOMEN'S HEALTH,
• NATIONAL OSTEOPOROSIS FOUNDATION,
• THE NORTH AMERICAN MENOPAUSE SOCIETY
• SOCIETY FOR THE STUDY OF REPRODUCTION,
• SOCIETY OF OBSTETRICIANS & GYNAECOLOGISTS OF CANADA,
• SIGMA CANADIAN MENOPAUSE SOCIETY.
Not on the list: American College of Obstetrics and Gynecology (ACOG)
HORMONAL THERAPY
• HRT INCREASED EXPONENTIALLY BETWEEN THE 1960S AND THE MIDDLE OF THE 1990S,
• 1999 AN ESTIMATED 20 MILLION POSTMENOPAUSAL WOMEN WERE USING HRT WORLDWIDE.
• THE POTENCY OF ESTROGENS IN HRT PREPARATIONS IS 6 TIMES LOWER THAN THE POTENCY OF ETHINYL ESTRADIOL CONTAINED IN CURRENTLY AVAILABLE OCPS
• UNOPPOSED ESTROGEN REPLACEMENT IS ASSOCIATED ^ RATES OF ENDOMETRIAL HYPERPLASIA AND CANCER: WOMEN WITH UTERUS'S NEED TO PROTECT WITH PROGESTERONE,
• WITH HYSTERECTOMY: ESTROGEN ALONE
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THE WHI……… WHY THINGS CHANGED
COMPOUNDS: DRUG QUALITY AND SECURITY ACT
• IN 2008, FDA TOOK ACTION AGAINST SEVEN COMPOUNDERS OF BHT FOR FALSE AND MISLEADING CLAIMS.
• FDA FOUND THAT THE LEVELS OF HORMONES WERE NOT WHAT WAS STATED ON THE PRESCRIPTION
• IN 2013, AFTER AN OUTBREAK OF INFECTIONS AND SOME RESULTING DEATHS FROM A COMPOUNDED DRUG, CONGRESS PASSED THE DRUG QUALITY AND SECURITY ACT
• COMPOUNDERS THAT MAKE UP ANY HORMONE PRESCRIPTION CONTAINING ESTRIOL (WHICH IS NOT AN FDA-APPROVED DRUG) MUST OBTAIN AN INVESTIGATIONAL NEW DRUG APPLICATION (IND)
ESTROGENS USED IN HRT CONJUGATED EQUINE ESTROGENS (CEE/CE)
• COMPLEX COMPOSITION OF AT LEAST 9 DIFFERENT ESTROGENS
• 1.25 MG OF CCE BEING EQUIVALENT TO MUCH LESS THAN 50 MICRG OF ETHINYL ESTRADIOL
MICRONIZED ESTRADIOL
• 17 BETA ESTRADIOL
• ESTERIFIED ESTROGEN
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HT STARTING DOSAGES • LOWER DAILY DOSES TYPICALLY USED WITH SYSTEMIC ET:
• 0.3 MG ORAL CE/CEE • 0.5 MG ORAL MICRONIZED 17ß-ESTRADIOL • 0.014-0.025 MG TRANSDERMAL 17ß-ESTRADIOL PATCH
• TYPICAL LOWEST DOSES OF PROGESTIN: • 1.5 MG ORAL MEDROXYPROGESTERONE ACETATE • 0.1 MG ORAL NORETHINDRONE ACETATE • 0.5 MG ORAL DROSPIRENONE • 50 MG ORAL MICRONIZED PROGESTERONE
NAMS position statement. Menopause 2010.
ESTROGEN THERAPY PRODUCTS APPROVED FOR POSTMENOPAUSAL USE IN THE US
Oral products Composi:on Product name(s) Range of available dose strengths Conjugated equine estrogens
Premarin 0.3-‐1.25 mg
Synthe:c conjugated estrogens, A*
Cenes:n 0.3-‐1.25 mg
Synthe:c conjugated estrogens, B**
Enjuvia 0.3-‐1.25 mg
Esterified estrogens Menest, EstraGyn 0.3-‐1.25 mg 17β-‐estradiol + Estrace, various
generics 0.5-‐2.0 mg
Estradiol acetate Femtrace 0.45-‐1.8 mg Estropipate Ortho-‐Est, Ogen 0.625 mg (0.75 mg estropipate, calculated
as sodium estrone sulfate 0.625 mg) to 5.0 mg (6.0 mg)
Transdermal products
Composi:on Product name(s) Dose details
17β-‐estradiol matrix patch
Alora, Climara, Esclim, Fempatch, Menostar, Minivelle, Vivelle, Vivelle-‐Dot, various generics
0.014-‐0.1 mg delivered daily; applied once or twice weekly
17β-‐estradiol reservoir patch
Estraderm 0.05-‐0.1 mg delivered daily; applied twice weekly
17β-‐estradiol transdermal gel
EstroGel, Elestrin, Divigel Applied daily via metered pump or packet delivering 0.52-‐0.75 mg of 17β-‐estradiol in gel
17β-‐estradiol topical emulsion
Estrasorb 2 packets applied daily
17β-‐estradiol transdermal spray
Evamist
1 spray/d, up to 2-‐3/d if needed
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Vaginal products Composi:on Product name(s) Dose details 17β-‐estradiol vaginal cream* Vulvovaginal atrophy (VVA)
Estrace Vaginal Cream Ini:ally 2-‐4 g/d for 1-‐2 wk, followed by maintenance dose of 1 g/d (0.1 mg ac:ve ingredient/g)
Conjugated estrogens cream* Atrophic vagini:s, moderate-‐severe dyspareunia
Premarin Vaginal Cream For vaginal atrophy: 0.5-‐2 g/d for 21 d then off 7 d For dyspareunia: 0.5 g/d for 21 d then off 7 d , or twice weekly (0.625 mg ac:ve ingredient/g)
17β-‐estradiol vaginal ring Moderate-‐severe VVA
Estring Device containing 2 mg releases 7.5 µg/d for 90 days (for vulvovaginal atrophy)
Estradiol acetate vaginal ring Vasomotor symptoms, severe VVA
Femring Device containing 12.4 mg or 24. 8 mg estradiol acetate releases 0.05 mg/d or 0.10 mg/d estradiol for 90 days (both doses release systemic levels for treatment of vulvovaginal atrophy and vasomotor symptoms)
Estradiol hemihydrate vaginal tablet Atrophic vagini:s
Vagifem Ini:ally 1 tablet/d for 2 wk, followed by 1 tablet twice weekly (tablet 10 µg of estradiol hemihydrates, equivalent to 10 µg of estradiol; for vulvovaginal atrophy)
*N.B. Higher doses of vaginal estrogen are systemic, meant to relieve hot flashes as well as vaginal atrophy; the lower doses are intended for vaginal symptoms only even though a small amount does get absorbed.
Combina:on EPT products comparing estrogen and proges:n doses Product name(s) Estrogen Progestogen Prempro, PremPhase,PremPlus 0.3, 0.45 0.625 mg conjugated
Estrogens 1.5, 2.5 or 5 mg MPA
Femhrt (Ortho Novum 1/35, LoEstrin, Estrostep, Junel)
5 µg ethinyl estradiol
0.5, 1 mg norethindrone acetate
Ac:vella 0.5, 1 mg 17β-estradiol
0.1, 0.5 mg norethindrone acetate
Angeliq (Yasmin, Yaz, B-‐Yaz) 0.25, 0.5 mg 17β-estradiol
0.5, 1 mg Drospirenone
CombiPatch Twice a week
0.05 mg 17β-estradiol
0.14, 0.25 mg norethindrone acetate
Climara Pro Once a week
0.045 mg 17β-estradiol
0.015 mg Levonorgestrol
Other Oral products
Product name(s) dosage Estrogen Other
Duavee Moderate-‐ sever vasomotor symptoms
0.45 conjugated estrogens
Bazedoxifene 20mg
Osphena moderate-‐severe dyspareunia None
Ospemifene 60mg
Brisdelle Moderate-‐severe vasomotor symptoms
None Paraxe:ne 7.5mg
8/19/14
15
NON-HORMONAL PRESCRIPTION DRUGS (OFF-LABEL USE):
• ANTICONVULSANT: GABAPENTIN (NEURONTIN)
• ANTIDEPRESSANT
• SSRI: FLUOXETINE (PROZAC), PAROXETINE (PAXIL), ESCITALOPRAM (LEXAPRO)
• SNRI: VENLAFAXINE (EFFEXOR XR) AND DESVENLAFAXINE (PRISTIQ)
• ANTIHYPERTENSIVE: CLONIDINE (CATAPRES)
• HYPNOTIC: ESZOPICLONE (LUNESTA)
• NEUROPATHIC PAIN DRUG: PREGABALIN (LYRICA)
HORMONE TESTING • TESTING HORMONE LEVELS IS NOT REQUIRED
• THE OPTIMAL HORMONE LEVELS HAVE NOT BEEN ESTABLISHED.
• SYMPTOMS RESPONSE TO A PARTICULAR IS THE ONLY RELIABLE GUIDE.
• SALIVA TESTING IS NOT ONLY UNNECESSARY AND NOT BEEN PROVEN TO BE ACCURATE OR RELIABLE.
• BECAUSE HORMONE LEVELS VARY DAY TO DAY AS WELL AS THROUGHOUT THE DAY, EVEN A BLOOD TEST CANNOT ACCURATELY REFLECT THE BODY’S HORMONE LEVELS.
• THE COMMON HORMONE TEST THAT MAY BE FSH TO HELP DETERMINE IF A WOMAN IS IN MENOPAUSE
REFERENCES
• RICE,C., THOMPSON,J. ELECTING AND MONITORING HORMONAL CONTRACEPTIVES: AN OVERVIEW OF AVAILABLE PRODUCTS. 6/20/2006. USPHARMACIST.COM/CONTENT/D/FEATURED_ARTICLES/C/11635/#STHASH.D8CDJD0K.DPUF
• BOSTON COLLABORATIVE DRUG SURVEILLANCE PROGRAM, BOSTON UNIVERSITY MEDICAL CENTER, SURGICALLY CONFIRMED GALLBLADDER DISEASE, VENOUS THROMBOEMBOLISM, AND BREAST TUMORS IN RELATION TO POSTMENOPAUSAL ESTROGEN THERAPY. N ENGL J MED. 1974;29015- 19
• GOMES, M.; DEITCHER, S. RISK OF VENOUS THROMBOEMBOLIC DISEASE ASSOCIATED WITH HORMONAL CONTRACEPTIVES AND HORMONE REPLACEMENT THERAPY:A CLINICAL REVIEW ARCH INTERN MED. 2004;164(18):1965-1976.