Natural Hormones Replacement An Evidence and Practice Based Approach

Transcription

1 Natural Hormones Replacement An Evidence and Practice Based Approach Andres Ruiz, PharmD, MSc, FACA President/Partner Stonegate Pharmacy PRESENTED BY THE AMERICAN COLLEGE OF APOTHECARIES 2830 SUMMER OAKS DRIVE BARTLETT, TN COPYRIGHT ACA This document is the property of the American College of Apothecaries. These materials may not be copied, photocopied, reproduced, translated, or distributed in any form or by any means without the prior written consent of the American College of Apothecaries.

2 Disclosures Andres Ruiz declare(s) no conflicts of interest, real or apparent, and no financial interests in any company, product, or service mentioned in this program, including grants, employment, gifts, stock holdings, and honoraria. The American College of Apothecaries is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education.

3 Learning Objectives At the conclusion of this program, the participating pharmacist or technician will be able to: Recount the history of hormone replacement therapy with regard to menopause and testosterone replacement in men Introduce the mechanism of action of hormone replacement therapy Review the physiology of men with regard to testosterone Review the history of Testosterone replacement therapy in Men

4 WOMEN

5 Introduction Such early depletion of oocytes in the human ovary is biologically remarkable since, apart from in a few strains of laboratory mice, follicle attrition does not take place in most species until the end of life, if at all. Roger Gosden, Ph.D., D.Sc.

6 Background Natural menopause: 12 months of amenorrhea due to the absence of ovarian follicles Menopause typically occurs in women between years of age with a mean age of 51.4 years

7 History of Bio-Identical Hormone Replacement Therapy (BHRT) Premarin Progesterone BHRT Emmenin Ovarin

8 Mechanism of Action Estrogens Progesterone

9 Mechanism of Action: Estrogen

10 Estrogen: Binding and Production E2 is bound to both sex hormone binding globulin (SHBG) and albumin ~37% is bound with high affinity to SHBG ~61% with low affinity to albumin ~1-2% is free and unbound Estrogen levels typically from pg/ml during a menstrual cycle to 5-20 pg/ml during menopause

11 E2 Production Variations

12 Estrogens Receptors: Alpha and Beta ER alpha and beta are the two ER and exhibit the most variation in there ligand binding domains ER gamma has been discovered but not been fully characterized ER alpha locations: ovarian stroma, uterus, endometrium, vagina, mammary gland, placenta, liver, central nervous system (CNS), cardiovascular system, adipose tissue, skin, sebaceous glands, and bone

13 Estrogens Receptors: Alpha and Beta ER beta locations: cardiovascular system, ovarian follicles, urogenital tract, mammary gland, intestinal mucosa, lung parenchyma, bone marrow, immune system, bone, brain, endothelial cells, muscle, skin, and prostate gland ER beta and alpha can have different and sometimes opposite effects More than 90% of ER beta expressing cells do not proliferate (exception uterus)

14 Mechanism of Action: Progesterone

15 Progesterone: Binding and Production Majority of the circulating P4 is bound to serum proteins ~17% is bound with high affinity to CBG ~80% with low affinity to albumin ~3% is free and unbound P4 levels vary from 25 ng/ml (luteal phase) to 200 ng/ml (pregnancy), and below 0.7 ng/ml during menopause

16 P4 Production Variations

17 Progesterone Receptors: A and B P4 s actions occur via genomic interactions and rapid non-genomic interactions with membrane binding sites PRA and PRB are equivalently expressed in most target cells PRA: transcriptional repressor and PRB: transcriptional activatorpra may suppress transcriptional activity of PRB, ER, androgen receptor, and glucocorticoid and mineralcorticoid receptors

18 Progesterone Receptors: A and B PR locations: uterine epithelial, stromal, and smooth muscle cells; mammary gland; ovarian surface epithelium; ovarian stroma and luteal cells; pulmonary parenchymal cells; and selected pituitary parenchymal cells, CNS, uterus, pancreas, bone, and tissues of the lower urinary tract Normal breast tissue PRA:PRB is 1:1 ratio altered in breast cancer

19 Mechanism of Action: Testosterone

20 Testosterone: Binding and Production Testosterone is highly protein bound ~99% is bound with high affinity to SHBG ~1-2% is free and unbound Testosterone levels production varies from 0.1 to 0.4mg/day Primarily produced via peripheral conversion (~50%), followed by ovarian (25%), and adrenal (25%) production Circulation levels vary from 20 and 60 ng/dl Levels are smallest early in follicular phase with a ~20% increase midcycle

21 Testosterone Production Variations

22 Androgen Receptor Testosterone actions occur via genomic interactions and rapid nongenomic interactions with membrane binding sites Single AR with two different ligand binding domains AR A and B AR locations: Pancreas, stomach, adrenals, prostate, liver, coagulation glands, skeletal muscle, spleen, seminal vesicles, harderian glands, Kidney, Preputial glands, thyroid glands, cowper s glands, infraorbital lacrimal glands, exorbital lacrimal glands, submaxillary glands, lungs, heart muscle, thymus, and blood cells.

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24 MEN

25 History of Testosterone Replacement Therapy (TRT) Capon Brown- Sequard Testosterone The Male Climacteric

26 Physiology of Men: Testosterone (P)ADAM Gradual Decline in serum T after 40y/o Higher decline in free T Low T not clearly defined Total T <300ng/dl (<10.4nmol/L) Symptoms

27 Low Testosterone Symptoms do not always correlate Common Symptoms: Lethargy, reduced concentration, ED, low libido, osteoporosis/fracture, sleep disturbance, irritability, depressed mood, obesity, lack of physical exercise and other lifestyle issues, relationship difficulties and/or occupational or financial stresses.

28 Defining Low Testosterone Araujo and colleagues: Best correlation to date Low Total T <300ng/dl Low Free T <5ng/dl Specific symptoms (1) low libido, ED, or osteoporosis Non-Specific Symptoms (2 or more) sleep disturbance, depressed mood, lethargy, or low physical performance Araujo AB. E Prevalence N T R E of P symptomatic R E N E U androgen R S H deficiency I P in men. M J Clin E N Endocrinol T O R I Metab. N G E D U C A T I O N

29 Araujo AB. E Prevalence N T R E of P symptomatic R E N E U androgen R S H deficiency I P in men. M J Clin E N Endocrinol T O R I Metab. N G E D U C A T I O N

30 Need More Information? Andres Ruiz, PharmD, MSc, FACA President/Partner Stonegate Pharmacies