Taking Action:BHRT Prescribing

OptionsRuth Hobson, ND and Laura Neville, ND

Staff Physicians Labrix LLC

Objectives

• Differentiate nomenclature for various hormone treatments

• Understand advantages and disadvantages of utilizing compounded hormones

• Understand dosage considerations and guidelines including:

• Routes of administration • Potencies• Schedules

• Become comfortable writing Rx’s for compounded BHRT formulations

Synthetic vs. Natural vs. Bioidentical

• Synthetic hormones are man-made• May or may not be derived from a

“natural” source, e.g. medroxyprogesterone (Provera)

• Typically refers to conventional HRT• ALL hormones used in supplementation

are technically synthetic. Our bodies do not produce the enzymes necessary to convert starter materials into hormones

Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. 2009; 121: 73-85.

Synthetic vs. Natural vs. Bioidentical

Natural hormones occur in nature.• Human bioidentical hormones

are not found in nature• Most commonly derived from

yam (dioscorea) or soy

Sites CK. Bioidentical hormones for menopausal therapy. Womens Health. 2008; 4: 163-71.

Synthetic vs. Natural vs. Bioidentical

Bioidentical hormones share the same molecular structure as the body’s own hormones.• Always synthetic – must be

produced in a laboratory

Whelen AM, et al. Defining bioidentical hormones for menopause-related symptoms. Pharm Pract. 2011; 9: 16-22.

BHRT availability

• Hormone supplementation is available:• Over the counter

• Progesterone cream • DHEA• Estradiol* • Estriol

• By prescription• Non-compounded

• (Climara, Vivelle-dot, generic estradiol patches, estrogel, etc.) • Compounded

• (Biest, progesterone, DHEA, testosterone, cortisol)

Ruiz AD, et al. Effectiveness of compounded bioidentical hormone replacement therapy: an observational cohort study. BMC Womens Health. 2011; 11[Epub].

Bio-Identical Pharmaceuticals

• Pharmaceuticals such as: Estrace, Estrogel, Evamist, Vivelle, Climera, Alora, Estroderm and others contain ONLY ESTRADIOL

• Estriol is not currently FDA approved to treat women with menopausal symptoms

• Always give progesterone when givingestradiol

• There are fewer bio-identical progesterones on the market:

• Prometrium – micronized oral • Crinone – 8% vaginal gel (pregnancy)

Holtorf K. The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy? Postgrad Med. 2009; 121: 73-85.

Compounded BHRT• Estrogens

• Estrone (E1)• Estradiol (E2)• Estriol (E3)

• Progesterone (Pg)• DHEA• Testosterone (T)• Cortisol• Thyroid

• Thyroxine (T4)• Liothyronine (T3)

Understanding the controversy: Hormone testing and bioidentical hormones. North American Menopause Society. 2006.

Routes of administration matter

• Transdermal• Cream/Gel• Patch

• Oral• Sublingual• Injection (IM, SubQ)• Subcutaneous pellets

Abbas A, et al. Contrasting effects of oral versus transdermal estrogen on serum amyloid A (SAA) and high-density lipoprotein-SAA in postmenopausal women. Arterioscler Thromb Vasc Biol. 2004; 24: e164-67.Iftikhar S, et al. Use of bioidentical compounded hormones for menopausal concerns: cross-sectional survey in an academic menopause center. J Womens Health. 2011; 20: 559-65.Cicinelle E, et al. Direct transport of progesterone from vagina to uterus. Obstet Gynecol. 2000; 95: 403-6.

Transdermal

• Advantages:• Easily monitored via salivary hormone testing• Ease of use• Not subject to 1st pass effect• Ability to alter dose as needed• Patches: steady release of hormone

• Disadvantages:• Risk of transference to others• Small risk of contamination to saliva sample• Can be stored in adipose when applied to adipose-rich

areas (i.e. abdomen, breast, etc)L'hermite M, et al. Could transdermal estradiol + progesterone be a safer postmenopausal HRT? A review. Maturitas. 2008; 60: 185-201.

Oral• Advantages:

• Easily monitored via salivary hormone testing• Ease of use

• Disadvantages:• Subject to 1st pass effect

• Estrogen: lowers IGF1 levels, raises acute phase proteins and increases risk of CV disease

• Progesterone: majority metabolized to allopregnanolone (works at GABA receptors and may be beneficial for women with sleep difficulties)

Abbas A, et al. Contrasting effects of oral versus transdermal estrogen on serum amyloid A (SAA) and high-density lipoprotein-SAA in postmenopausal women. Arterioscler Thromb Vasc Biol. 2004; 24: e164-67.

Sublingual

• Advantages:• Ease of use• Little to no exposure to others• Ability to alter dose as needed• Not subject to 1st pass effect – unless swallowed

• Disadvantages:• Slightly harder to monitor via saliva d/t increased risk of

contamination

Mahmud K. Natural hormone therapy for menopause. Gynecol Endocrinol. 2010; 26: 81-85.

Intramuscular/SubQ

• Advantages:• Little to no exposure to others• Not subject to 1st pass effect

• Disadvantages:• Injection/needles• Inconsistent supply of hormone (typically dosed weekly

or bi-weekly)

Cicinelle E, et al. Direct transport of progesterone from vagina to uterus. Obstet Gynecol. 2000; 95: 403-6.

Pellets

• Advantages:• Little to no exposure to others• Not subject to 1st pass effect• Semi-permanent (3-6 month dosing)

• Disadvantages:• Surgically implanted (invasive)• Inability to alter dose once implanted

Stanczyk, F.Z., et.al. (1988). A randomized comparison of nonoral estradiol delivery in postmenopausal women. American Journal of Obstetrics and Gynecology, 159(6). pp. 1540-46.

BHRT considerations: estrogen

• Supplement when indicated • Consider conception goals when determining

dosage schedule premenopausal women• Never supplement estrogen without balancing with

progesterone supplementation• Consider E2/E3 combination (Biest)• Consider topical delivery over oral delivery

Your patients on Premarin and other oral estrogens…caution:Oral estrogens can:

• Increase blood pressure• Increase triglycerides• Increase estrone• Cause gallstones• Elevate liver enzymes

• Decrease IGF-1 levels• Increase SHBG• Increase C-reactive protein• Increase phase 1

inflammatory markers

Goodman MP. J Women’s Health (Larchmt). 2011 Oct 19 Are All Estrogens Created Equal? A Review of Oral vs. Transdermal Therapy.

Estriol supplementation

• Most often prescribed as vaginal suppository or cream, addressing vaginal dryness and boosting EQ

• Over the counter: creams & suppositories• Rx: Compounded only

• Starting dose:• 1 mg pv qhs x 1-2 weeks, followed by 1-4 times

weekly as needed for comfort

BHRT considerations: progesterone• Progesterone sensitizes estrogen receptors• Consider conception goals when determining

dosage schedule for premenopausal women• Dosage route: Majority of oral progesterone is

metabolized to allopregnanolone by the liver• Induces a calming affect as a positive modulator of

GABA-A receptors—excellent sleep aid for some pts

Administration of progesterone produces mild sedative-like effects in men and women. Söderpalm AH, Lindsey S, Purdy RH, Hauger R, Wit de H. Psychoneuroendocrinology. 2004 Apr;29(3):339-54.Anxiolytic metabolites of progesterone: correlation with mood and performance measures following oral progesterone administration to healthy female volunteers. Freeman EW, Purdy RH, Coutifaris C, Rickels K, Paul SM. Neuroendocrinology. 1993 Oct;58(4):478-84.Allopregnanolone concentration and mood--a bimodal association in postmenopausal women treated with oral progesterone. Andréen L, Sundström-Poromaa I, Bixo M, Nyberg S, Bäckström T. Psychopharmacology (Berl). 2006 Aug;187(2):209-21.

BHRT considerations: testosterone

Requires DEA number• Only FDA approved testosterone product for women is

Estratest (esterified estrogens and methyltestosterone)• Note: hepatotoxic

• Topical supplementation (via Rx with compounding pharmacy) for insufficiency

• Testosterone supplementation may contribute to estradiol levels via aromatization

• Possible to support testosterone levels via DHEA supplementation, if indicated

BHRT considerations: DHEA

• Can be oral or topical (competes with P4 topically)• Typically dosed orally as DHEA may compete for

absorption with other transdermal hormones, particularly progesterone

• DHEA can convert to estrogen and testosterone in both men and women.

• Be careful with supplementation with overweight women—can elevate estrogen levels

Slim, Sane and Sexy. pp 165-166 Mead J, Lommen E. 2009 ISBN-10: 1929841507 Fountain of Youth Press

BHRT considerations: 7-keto DHEA• While it is commonly stated that 7-keto DHEA does

not convert to testosterone or estradiol, we consistently observe this conversion.

• When estradiol and/or testosterone are elevated, supplementing with 7-keto DHEA is NOT a better option.

Cortisol Supplementation

• Oral dosing for established (Phase 3) adrenal dysfunction

• Rx: Cortef, hydrocortisone, compounded formulas

• To avoid suppression, max dose of 20 mg QD• Starting dose:

• 5-10 mg upon waking and 5-10 mg at noon

Compounding pharmacyPharmacy compounding is the art and science of preparing personalized medications specifically formulated for an individual. Compounded medications are “made from scratch.” Individual ingredients are mixed together in the exact strength and dosage form required by the patient. This method allows the compounding pharmacist to work with the patient and the prescriber to customize a medication to meet the patient’s specific needs.

Regulation

Myth: Compounded medications are not regulated because they are not subject to FDA regulation.

Regulation

• Compounded medications are not regulated by the FDA because they are governed at a state level, not federal.

• Compounding has always been regulated by state boards

• Standards set by the United States Pharmacopeia (USP) are used in compounding

• Accredited pharmacies follow standards set by The Pharmacy Compounding Accreditation Board (PCAB)

International Academy of Compounding Pharmacists. Frequently Asked Questions About Compounding. Available at: http://www.iacprx.org/displaycommon.cfm?an=1&subarticlenbr=2 . Accessibility verified October 29, 2012.

Professional Compounding Centers of America

http://www.pccarx.com

The International Academy of Compounding Pharmacists

www.iacprx.org

Understanding the controversy: Hormone testing and bio-identical hormones. North American Menopause Society. 2006.

While no single route of administration will be right for every patient, and BHRT formulation decisions are individualized

on a patient-by-patient basis, bioidentical transdermal formulations

are increasingly common, widely available and well tolerated by most

patients.