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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    

8/19/14  

14  

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.