Hormone Replacement Therapy: The Evidence and the Clinicians Dilemma Victor S. Sierpina, MD Alvah Cass, MD Daniel Freeman, PhD

Bio-identical Hormones Hormones that are identical to those produced in the human body (may be synthetically produced) –Estrone, estradiol, estriol ( Ortho-Est,Estrace, Estraderm, Climara) –Progesterone (ProGest, Fem-Gest, Progonol) –Testosterone –DHEA

Natural Progesterones? Compounding Pharmacies Mexican Wild Yam (Must add UPS Progesterone to topical cream to be bioavailable) Compounding pharmacies: Bi-Est, Tri-Est, Micronized Progesterone ;

Ovarian Steroidogenesis

Altered andNatural Hormones Conjugated or otherwise modified from the original structure May have multiple components, bioactivity, bioavailability, metabolites Premarin®, conjugated equine estrogen has 90 different hormonal components

Differences in Function/Structure TestosteroneEstradiol

Differences in Structure Methylated ProgesteroneProgesterone

Basics of Menopausal Care Regular exercise Social support Meditation, relaxation, sleep Quit smoking/alcohol Dietary phytoestrogens –Soy –Celery, fennel, parsley –Nuts, seeds –Flaxseed

Phytoestrogens Soy Black Cohosh Dong Quai Red Clover Chaste Berry Tree Licorice Evening Primrose Oil Ginseng

Botanicals Cimcifuga racemosa (Black cohosh) 1-2 g tid; 2 mg bid (27-deoxyacteine) Angelica sinensis (Dong quai) 1-2 g tid Glycyrrhiza glabra (Licorice) 1-2 g tid Vitex agnus-castus (Chaste berry)1-2 g tid Ginseng mg/d

Conclusions Jury still out on safety of HRT Bio-identical HRT has not been evaluated in clinical trials Are risks of HRT due to the hormones, their metabolites, methods of administration

Conclusions Botanical medicines useful to treat menopausal sx ? Effect on osteoporosis, CV dz Progesterone alone may tx both menopausal sx and osteoporosis (controversial for osteoporosis when used alone)

BOTTOM LINE – HRT for menopausal sx is likely safe for up to 4-5 yrs –Longer use (10-15 yrs) may create increased risk for some women –Dont HRT as CV tx or preventive –Individualize risk/benefit ratio and choice for each pt.