New FOUNDATIONAL PRINCIPLES OF BIO-IDENTICAL · 2018. 10. 24. · PAP smear Mammogram or thermography Bone Mineral Density (BMD) BASELINE INVESTIGATIONS. PROGESTERONE 31. 32 • Used

FOUNDATIONAL PRINCIPLES OF BIO-IDENTICAL HORMONE REPLACEMENT THERAPY:

THE WHO, WHAT, WHERE, WHEN, AND WHYS

Dr. Kristy A. Prouse, MD, FRCSC (OB/Gyn)2

HOUSEKEEPING

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Download the Slides Questions No photography, audio, or video

recordings

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https://education.lp3network.com/WCC2018

DISCLAIMER

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DISCLAIMER: The information contained in this program, which may include treatment modalities,diagnostic and therapeutic information, and instructions related to regulatory guidelines and currentstandards of practice for pharmacy compounding, is FOR EDUCATIONAL PURPOSES ONLY and shouldnot be taken as a treatment regimen, product indication, suggested treatment modality, or suggestedstandard of practice. NOTE TO MEDICAL OR ALLIED HEALTH PROFESSIONAL: Any treatments,therapies, or standards of practice must be fully investigated and prescribed by a duly licensedmedical practitioner in accordance with accepted professional standards and compendia. Anyregulatory or practice standard must be fully investigated by a licensed pharmacist in accordancewith accepted professional practice standards and compendia.

ACCREDITATION

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PHARMACIST & PHARMACY TECHNICIAN CREDITS

CPE Consultants, LLC is accredited by the Accreditation Council for Pharmacy Education as

a provider of continuing pharmacy education and complies with the Accreditation Standards

for continuing education activities.

Activity Type Pharmacist Pharmacy Technician

Pharmacist UAN 0864-9999-18-084-L01-P 0864-9999-18-084-L01-T

Credits 1 CPE Hours = 0.1 CEUs 1 CPE Hours = 0.1 CEUs

Release Date October 28th 2018 October 28th 2018

Expiration Date October 28th 2019 October 28th 2019

ACCREDITATION

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HOW TO OBTAIN CREDITS

Create your LP3 Account1

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Note the Tacking Code at the END OF THE PRESENTATION

Register for WCC 2018 Workshops

Submit a completed Evaluation (within 14 days) online for each Workshop.

5 Statement of credits will be provided within 30 days.

KRISTY A. PROUSE, MD, FRCSC

• Associate Professor, University of Toronto-Faculty of Medicine

• B.A. Psychology and B.Sc. In Genetics and Cell Biology

• Specialized in Anti-aging and Regenerative Medicine

• Established the Institute for Hormonal Health in 2011 and the IHHeLP Initiative

I have no financial relationships to disclose

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LEARNING OBJECTIVES

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PHARMACISTS

1. Define differences between bioidentical hormones and non-bioidentical hormones.

2. Review steroidogenic pathway.

3. Compare conventional HRT with bioidentical HRT in terms of clinical efficacy, breast

cancer risk, and cardiovascular risk.

4. Recognize the importance of diagnostic testing.

5. Identify principals of prescribing BHRT, dosing BHRT, applying BHRT, and

troubleshooting BHRT.

LEARNING OBJECTIVES

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PHARMACY TECHNICIANS

1. Define differences between bioidentical hormones and non-bioidentical hormones

2. Recognize the clinical benefits and demand for personalized BHRT.

3. Identify elements that should be found in a BHRT prescription, including dosage

strength and dosage form.

4. Evaluate common challenges encountered with BHRT formulations.

PHYSIOLOGY OFSEX HORMONES

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PHYSIOLOGY OF THE MENSTRUAL CYCLE

By Lyrl - Derived from Image:MenstrualCycle.png, an image made by the user Chris 73.

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STEROIDOGENIC PATHWAYS

Progesterone

Aldosterone

Cortisol

Testosterone

Estrogens

cholesterol

ProgesteroneTestosterone

Estrogens

Aldosterone

CLASSIFICATION AND SYMPTOMATOLOGY OF SEX

HORMONE IMBALANCES

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IMBALANCES

• Estrogen Dominance

• Relative Estrogen Dominance

• Elevated Androgens

CLASSIFICATION IMBALANCE AND DEFICIENCIES

IMBALANCES

• Estrogen

• Progesterone

• Testosterone

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ESTROGEN DOMINANCE

• Perimenopausal Sx

• Anovulation

• PMS

• Menorrhagia

• Dysmenorrhea

• Cyclical breast tenderness

• Consequences of Estrogen Dominance

• Endometriosis

• Fibroids

• Breast/cervical/uterine cancer

• Thyroid related problems

SYMPTOMATOLOGY

ELEVATED ANDROGENS (FEMALE)

• Male pattern hair loss

• Male pattern hair growth

• Acne/oily skin

• Irritability/Aggressiveness

• Breast tenderness

• Hypersexuality

• Clitoromegaly

• Deepening voice

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LOW ESTROGEN OR PROGESTERONE• Hot flashes

• Memory decline

• Anxiety

• Insomnia

• Weight gain

• Vaginal dryness

• Painful intercourse

• Decreased libido

• Crawly skin

• Frequent bladder infections

SYMPTOMATOLOGY

LOW TESTOSTERONE (FEMALE)

• Decreased libido

• Decreased arousal/orgasm

• Decreased nipple sensation

• Loss of muscle mass

• Loss of vitality

• Decreased exercise tolerance

DIAGNOSIS OF SEX HORMONE IMBALANCES

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• Symptomatology:

Imbalances/Deficiencies

• Physical Examination:

breast and pelvic

• Saliva: historically gold

standard for baseline

• Dried urine spot: baseline

or for those on hormone

replacement

• Bloodwork:

underestimates hormone

levels

DIAGNOSIS

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CASE INFORMATION

• 47 y/o peri-menopausal female not

on any hormone replacement

therapy complaining of heavy

periods with breast tenderness in

the week before her period. She is

complaining of new onset anxiety

and sleeplessness.

CASE STUDY #1

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CASE INFORMATION

• 57 year old PM female complaining

of hot flashes, sleep disruption and

vaginal dryness. Further questionig

reveals decreased sex drive

unrelated to vaginal dryness and

painful intercourse.

CASE STUDY #2

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CASE INFORMATION

• 47 yo post-menopausal female

started on Estrogel 1 pump and

Prometrium 100mg po by her family

doctor without testing. She is

largely asymptomatic however with

questioning she does note

occasional breast tenderness. She

has not had any PV bleeding and

endometrial thickness is 4mm.

CASE STUDY #3

BIO-IDENTICAL HORMONE REPLACEMENT THERAPRY

(BHRT)

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• Bio-identical Hormone: have a chemical structure identical to endogenous human

hormones but are chemically synthesized such as estriol, estradiol, progesterone and

testosterone.

• Non-bio-identical hormones: are not structurally identical to human hormones and

may either be chemically synthesized such as MPA (progestin) or derived from a

nonhuman source such as CEE (conjugate equine estrogens).

• Progesterone: our own endogenous hormone.

• Progestins: synthetic chemicals that mimic the effects of progesterone by binding to

progesterone receptors e.g., MPA

• Progestogens: an umbrella term for both progesterone and progestins.

DEFINITIONS

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BIO-IDENTICAL VS CONVENTIONAL HRT

• Holtorf, K. Postgraduate Medicine, 2009.

Bio-identicalProgesterone

SyntheticProgestins

Clinical Efficacy Best Good

Physiologic actions on breast tissue

Protective Negative

Risk of breast cancer

Protective Increased

Risk of CVD Protective Increased

Risk of DVT None None

Bio-identicalE2/E3-TD

SyntheticEstrogens

Breast cancer risk Protective Increased

DVT risk None Increased

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FDA/HEALTH CANADA APPROVED HORMONES


Brand Name

Estrace po/pv

Esclim TD patch

Climara TD patch

Estraderm TD patch

Vivelle TD patch

Estrogel TD gel

Estrasorb TD cream

Estring vaginal ring

Femring vaginal ring

Vagifem vaginal tablet

Prometrium po

Procheive 4% vaginal gel

Type/Source Bio-identical?

17 Beta-estradiol/plant Yes








Estradiol acetate Yes

Estradiol hemihydrate Yes

Progesterone micronized Yes

Progesterone Yes

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FDA/HEALTH CANADA APPROVED HORMONES


Brand Name

Premarin po/pv

Estinyl po

Provera po

Ovrette po

Micronor po

Prempro po

FemHRT po

Combipatch TD

Climara Pro TD

Type/Source Bio-identical?

Conjugated equine estrogens No

Ethinyl estradiol No

Medroxyprogesterone acetate (MPA) No

Norgestrel No

Norethindrone No

CEE and MPA No

Ethinyl acetate and norethindrone acetate No

17 beta estradiol and norgestimate No

17 beta estradiol and levonorgestrel No

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• BiEst (Estradiol/Estriol) TD

• Estriol pv

• Progesterone po/TD

• Testosterone TD

• 7-keto DHEA SL/TD

• DHEA SL/TD

COMPOUNDED BIO-IDENTICAL HRT

PRESCRIBING BIO-IDENTICAL HORMONES

28Copyright © 2018 LP3 Network

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PRINCIPLES OF PRESCRIBING HRT

• Start low and go slow

• Balance

• Physiologic ranges

• Understand downstream hormones

• Avoid down regulation of receptors

• Conversion dosing TD po (x4-5)

• Perform baseline investigations

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Trans-vaginal pelvic ultrasound (TVUS)

PAP smear

Mammogram or thermography

Bone Mineral Density (BMD)

BASELINE INVESTIGATIONS

PROGESTERONE

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• Used to balance estrogen and to support cortisol

production

• TD or po applications most common

• Prescribed orally for sleep/anxiety

• Given cyclically to menstruating woman

• Given daily (with a day of rest) to post-menopausal

woman

• Initiate dose according to test results and titrate to

symptoms

PROGESTERONE

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TYPICAL PROGESTERONE DOSING

Pre-Menopausal

• Compounded progesterone 50-150mg SR po qhs D15-28 (or until menses begins if before day 28)

**increments of 25mg

• Compounded progesterone cream 5-30mg TD qhs D15-28 (or until menses begins if before day 28)

**increments of 5mg

Post-Menopausal

• Compounded progesterone 75-175mg SR po qhs Monday to Saturday


• Compounded progesterone cream 10-30 mg TD qhsMonday to Saturday

**increments of 5mg

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OVER-REPLACEMENT OF PROGESTERONE

Slow to wake up or “groggy” in the morning

Breast tenderness Cystic acne Low mood Swelling in hands and legs Sluggish bowels/bloating Hot flashes (body interprets

estrogen as too low) Insulin resistance and

weight gain

BI-EST

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ESTROGEN METABOLISM

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• Used to replace estrogen when objectively deficient

• Combination of estradiol and estriol (20:80) or

(50:50)

• Transdermal application only

• Given daily (with a day of rest) to post-menopausal

woman

• Initiate dose according to test results and titrate to

symptoms

• Must be balanced with progesterone

BI-EST

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TYPICAL BIEST DOSING

Pre-Menopausal

• Compounded BiEStcream 80:20 (E3/E2) 0.1-0.25mg TD OD day 1-25

**Increments of 0.05mg

Post-Menopausal

• Compounded BiEST cream 80:20 (E3/E2) 0.5-1.75mg TD BID Monday to Saturday

**Increments of 0.5mg

• Surgical menopause may require higher doses to manage symptoms

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OVER-REPLACEMENT OF ESTROGEN

Irritability or weepiness

Acne Breast tenderness Swelling Post-menopausal

vaginal bleeding

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TROUBLESHOOTING ESTROGEN

Hot flashes worse at a certain time of day

Transition from perito post-menopausal dosing

Timing of switch from cyclic to daily hormones

ESTRIOL

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• Used for vaginal atrophy resulting in

bothersome vaginal dryness, painful

intercourse or recurrent urinary tract

infections

• Transvaginal application

• Administered in tapering doses at bedtime

• May be transferred to sexual partner

• May initiate without testing based on

symptoms and physical examination

ESTRIOL FOR UROGENITAL ATROPHY

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TYPICAL VAGINAL ESTRIOL DOSING

• Compounded Estriol vaginal cream 0.25-0.5 mg qhs x 2 weeks, then twice weekly thereafter

TESTOSTERONE

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• Used to replace testosterone when proven

deficient AND with symptoms of deficiency


• Administered Monday to Saturday

• Initiate dose according to test results and

titrate to symptoms

• Woman must have adequate endogenous

estrogen and if not, then estrogen

replacement to balance

• Elevated dihydrotestosterone (DHT)

• Downstream impact on estrogen

TESTOSTERONE REPLACEMENT

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OVER-REPLACEMENT OF TESTOSTERONE

Angry/aggressiveAcne/oily skin ClitoromegalyHirsutismDeepening of the

voice

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• Used to replace testosterone when proven

deficient AND with symptoms of deficiency


• Administered Monday to Saturday

• Initiate dose according to test results and

titrate to symptoms

• Elevated Dihydrotestosterone (DHT)

• Downstream impact on estrogen

TESTOSTERONE REPLACEMENT

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TYPICAL TESTOSTERONE DOSING

Female

• Compounded testosterone cream 0.5-1.25mg TD qam Monday to Saturday

**increments of 0.25mg

Male

• Compounded testosterone cream 40-120mg TD qamMonday to Saturday


***desired fertility-do not use testosterone****controlled substance

DELIVERY METHODS

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• Carrier bases

• Fillers

• Vaginal (E3)

• Application sites

CARRIER BASES FOR BHRT

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• Use base creams specified for HRT for stability

of API and penetration

• Allows for consistency in dosing

• Allows for consistent potency over time

• Can be used both transdermally and

transmucosally

• Choose hypoallergenic cream

• Choose paraben-free

CARRIER BASES FOR BHRT

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Progesterone is a BCS Class IV Drug(Class 4: Low Solubility –Low Permeability)

• Lactose (non-specific excipient)

• should be avoided for those with lactose allergies

• Poor powder blend flowability

• May interact negatively with various APIs

• Cellulose is considered a neutral filler

• Minimal if any adverse reations

• Does not improve dosage form (eg.,enhance drug

dissolution, improve chemical stability, increase

efficiency, reduce static of actives, etc.)

• Blended Excipients

PROGESTERONE CAPSULE FILLERS

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• Use a suppository base to avoid vaginal

irritation (instead of gels/creams)

• Hormones are lipophilic and so preparation

with a lipophilic base will provide slower

release

VAGINAL APPLICATION

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ESTROGEN/PROGESTERONE APPLICATION SITES

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TESTOSTERONE APPLICATION SITES

TRACKING CODE

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WCC2018HRT2

Documents

New FOUNDATIONAL PRINCIPLES OF BIO-IDENTICAL · 2018. 10. 24. · PAP smear Mammogram or thermography Bone Mineral Density (BMD) BASELINE INVESTIGATIONS. PROGESTERONE 31. 32 • Used