Professor TTUHSC Dept of Family and Community Medicine

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1 Stephen G. Dalton D.O. Adjunct Clinical Assistant Stephen G. Dalton D.O. Adjunct Clinical Assistant Professor TTUHSC Dept of Family and Community Medicine

2 1-The first hormone to become deficient in perimenopauseis A- estrogen B-progesterone C-testosterone D-DHEA

3 Higher testosterone levels promote prostate cancer? A-true B-false

4 The strongest estrogen is? A- E1-estrone B- E2-estradiol C- E3-estriol

8 Hormone Testing Blood levels- My preferred method of initial testing. Numerous drawbacks potentially present after treatment begins. 24 hour urine levels-a cumbersome reliable method of testing of hormones before and during treatment. Several potential pitfalls. Saliva testing-measures free bio-available hormone levels but froughtwith many potential collection and possible diagnostic problems. Much better now than in the past. Probably the best test method for adrenal fatigue and cortisol testing. Testing can help but- 80% clinical

11 E1=estrone: get some from conversion of E2. Normally 10% of estrogens but in menopause increases to 80%. E2=estradiol: Potent. Catachol and methoxy metabolites are protective. Normally 10% of estrogens, in menopause decreases to trace levels. E3=estriol: cancer protective. Normally 80% of estrogens, in menopause decreases to much lower levels. 80x weaker than estradiol. Offers breast cancer protection, maintains vaginal ph, prevents UTI s, no uterine lining stimulation, no clotting issues.

12 Estradiol(E2) Briefly It helps regulate the expression of over 300 genes. Metabolizes into beneficial estrioland other downstream metabolites. 2-hydroxyestrone being protective against breast cancer and 16-alphahydroxyestrone a breast cancer promoting hormone. Cardio and neuroprotective and well as 400 other functions in the body

13 Estriol(E3) and Urinary Health Vaginal estriolcream 0.5mg to 1mg/gram used every other night is highly effective for interstitial cystitis in women. There is an abundance of estrogen receptors in the bladder. Extremely well tolerated.

14 Menopause and Perimenopause Menopause - No menses for one year. Considered normal between ages yo; 51 average. Perimenopause years surrounding menopause Pre-menopause - Imbalances of hormones premenopausallymay contribute to a variety of symptoms.

15 Estrogen Deficiency Poor sleep Atrophic vaginitis Bladder dysfunction Depressed mood Decreased libido Cardiovascular disease Hot flashes Night sweats Poor memory, dementia Daytime sleepiness Osteoporosis

16 Estrogen Excess/Dominance Agitation/PMS Weight gain Anxiety Water retention Headaches Swollen or tender breasts Cold hands and feet Dry eyes Decreased sex drive Fatigue Magnesium deficiency Bloating Breakthrough bleeding Mood swings Poor sleep Achy joints Gallbladder disease Endometrial cancer Uterine fibroids Thyroid dysfunction PCOS Infertility

17 Estrogen Dominance Examples PMS- Day 1 the period begins. Day 13 use topical progesterone cream for 13 days or mg PO daily the second half of the cycle. Take magnesium mg daily also. Migraine headaches- if in the 2 nd half of the cycle near menses magnesium daily and progesterone just as for PMS. IV magnesium sulfate 1-2grams in 100ccNS with 100mg of vitamin B6 IV over 15 minutes also extremely effective. Also give an oral NSAID before or after the IV.

18 Synthetic vsbio-identical Conjugated equine estrogens are not bio-identical. It breaks down to 45% estronesulfate and 55% various equine estrogens. It is NATURAL to a horse, not a woman. It does happen to be very effective for hot flashes but will remarkably increase SHBG which will preferentially bind up testosterone making it essentially unavailable. For best results mimic nature. HUMAN nature!

19 Natural Progesterone Benefits Helps turn fat into energy Protects against prostate and breast cancer Improves sexual drive Helps normalize blood glucose and thyroid hormone function Improves nitric oxide production Decreases platelet aggregation Improves brain function Stimulates new bone formation Improves sleep and an anti-depressant Anti-inflammatory activity Prevents coronary vasospasm Decreases LDL, LDL oxidation, Lp(a), homocysteine

20 Progesterone (P4) Deficiency Symptoms Agitation and irritability (PMS gets worse before menopause) Aggressiveness Weight gain Water retention Headaches Swollen tender breasts bloating spotting or breakthrough bleeding Poor sleep, insomnia Endometriosis Menorrhagia Achy joints

21 Progesterone (P4) Usually the first hormone to become deficient in perimenopause.

22 Progestin (MPA) Side Effects Breast tenderness Bloating Increased appetite Decreased libido Acne Hair loss Counteracts estrogen s positive effects Depression Insomnia Irritability

23 DAWN Study. J Am Geriatric Soc 2008July; 56(7): Double blind placebo controlled with 50mg of DHEA daily Cognitive, life and sexual function evaluated No significant difference from placebo on side effects Healthy normal cognitive function promoted Increased testosterone (60%)and estrogen (40%) in women, not in men

26 DHEA No unique symptoms of deficiency but Low levels associated with -all cause mortality, cardiovascular mortality -osteoporosis -cancer -obesity, type 2 diabetes -immune dysfunction -autoimmune disease -depression and a loss of well being -hypertension - low libido and erectile dysfunction

27 DHEA facts DHEA is the most abundant circulating hormone sex steroid in women It provides a large precursor resevoirfor the intracellular production of androgens and estrogens Secreted by the adrenals and ovaries Levels for DHEAS and DHEA decline with age. IntravaginalDHEA has been shown to decrease dyspareunia Builds bone

28 Testosterone in Women Increases the sense of emotional well being Increases sexual interest Increases muscle mass and strength Helps maintain memory Helps skin from sagging Helps maintain bone strength Elevates norepinephrine in the brain

29 T deficiency Symptoms in Women Muscle wasting Decreased HDL Low self-esteem Fatigue Weight gain Dry, thin skin with poor elasticity Droopy eyelids Sagging cheeks, thin lips Anxiety

30 T side Effects in Women Oily skin Acne Deepening of the voice Increased facial hair Clitoral enlargement Too much libido, aggressiveness

31 Testosterone Excess Symptoms Hypoglycemia Anxiety Fatigue Salt and sugar cravings Agitation and anger Insulin resistance Hair loss and unwanted hair growth Acne Increased risk of heart disease Depression

32 Bio-identical Hormone Replacement in Women Balance estrogens, progesterone and testosterone Every woman has a unique balance Progesterone protects against breast cancer Delicate balance between estrogen and progesterone. Both are antagonistic and complimentary.

33 Unequal risks for breast cancer associated with different hormone replacement therapies: Breast Cancer Res Treat Feb 27, 2007 A.Fournier 80,377 post menopausal women No increase or decrease in breast cancer in women on estrogen and progesterone Estrogen plus MPA (Provera) had a RR r 69% increase risk of breast cancer. This proves that bio-identical hormones are safe

34 BJM 2012;345 by Schierbecket al 10 years of randomized treatment Oral HRT (estradiol, northindrone) early after menopause Significantly reduced risk of mortality, heart failure, and myocardial infarction No apparent increase risk of cancer, venous thromboembolism, or stroke

35 Hormone Delivery Methods in Women Compounded or commercial creams and capsules Sprays Patches Pellets Buccal or lozenge-bypasses the digestive track and first pass metabolism of the liver by absorption through the mucous membranes. Gels Pills- High first pass metabolism through the liver

36 Why not swallow estrogen pills? Oral HRT leads to higher 2-hydroxxyestrone and 16-alphahydroxyestrone metabolites Oral HRT raises triglycerides and VLDL Oral HRT increases CRP Increases the mean value of prothrombinactivation peptide and decreases mean anti-thrombin activity Associated with a significant decrease in mean tissue-type plasminogenconcentration and plasminogenactivator inhibitor activity and significant rise ifnthe global fibrinolytic capicity(increased thrombosis risk) Oral HRT increases RR of endometrial hyperplasia where vaginal application did not. It does not follow natures intended route

39 Daily Topical Cyclical Replacement Protocol Level One Estradiol(E2) 1mg/0.1cc Days 1-10 : Use 1 line Days 11-13: Use 2 lines Days 14-31: Use 1 line Progesterone (P4) 20mg/0.1cc Days 1-13: Use none Days 14-15: Use 1 line Days 16-21: Use 2 lines Days 22-31: Use 1 line

40 Level 2 Hormone Protocol E2 1mg/0.1cc Days 1-5: 2 lines Days 6-11: 3 lines Day 12: 4 line Days 13-14: 1 line Days 15-31: 2 lines P4 20mg/0.1cc Days 1-13: none Days 14-15: 1 line Days 16-19: 2 lines Day 20: 3 lines Days 21-22: 4 lines Days 23-24: 3 lines Days 25-26: 2 lines Days 27-31: 1 line

41 Level 3 Hormones E2 1mg/0.1cc Days 1-5: 3 lines Days 6-8: 4 lines Days 9-11: 5 lines Day 12: 6 lines Days 13-17: 2 lines Days 18-31: 3 lines P4 20mg/0.1cc Days 1-13: none Days 14-15: 2 lines Days 16-17: 3 lines Days 18-19: 5 lines Day 20: 6 lines Day 21: 7 lines Days 22: 6 lines Days 23-24: 5 lines Days 25-26: 4 lines Days 27-31:2 lines

42 Level 4 E2 1mg/0.1cc Days 1-5: 4 lines Days 6-8: 6 lines Days 9-11: 7 lines Day 12: 8 lines Days 13-14: 2 lines Days 15-17: 3 lines Days 18-31: 4 lines

43 Daily Cyclical Hormone Protocol Success 80% of women will do very well on level 1 or 2. Few will need higher doses and few will have trouble tolerating it. With oral or topical DHEA few women will need testosterone to help boost libido or control other menopausal symptoms. Oral DIM at any age helps reduce the risk of breast cancer by optimizing 2/16-hydroxyestrone ratios I usually recommend a 12.5mg iodine/iodide pill weekly or more often Remember what works best is to mimic nature!

46 T Deficiency: Signs and Symptoms Diminished libido Erectile dysfunction Difficulty achieving orgasm Decreased spontaneous erections Diminished energy Depressed mood Impaired cognition Reduced motivation decreased bone mineral density Decreased muscle mass and strength Increased body fat Gynecomastia Anemia Insulin resistence

47 Testosterone and Prostate Cancer Thus, there appears to be no compelling evidence at present to suggest that men with higher testosterone levels are at greater risk of prostate cancer or that treating men who have hypogonadismwith exogenous androgens increases this risk. Rhoden EL and MorgentalerA. N Engl J Med. 2004;

48 T and Prostate Cancer The origin of the general rule that T causes activation and enhanced rate of growth of prostate cancer was based on A single (one) patient! Huggins C et al. Cancer Research 1941; 1:293

49 Initial Workup of Low Testosterone DRE PSA Total and free testosterone Prolactin CMP, CBC, TSH and free T3 May consider LH, FSH, SHBG pregnenolone, DHEAS

50 Low T Replacement Testosterone cypionateweekly injections. Average dose 100mg IM or SQ weekly. 50 to 150mg range. Commercial transdermal gels or patches Compounded custom gels, lipodermalcreams, or creams. Often mg/g T. Apply 1 gram topically 5 to 7 days a week. 50 to 200mg a day. Implanted T pellets 75mg. Repeat implantation every 3 to 6 months. 5 to 15 pellets. HCG units/week. 250 iudaily or 1000 iu twice a week

51 Testosterone Side Effects Decreased sperm count Decreased testicle size More libido Increase in H and H Possible fluid retention Hair growth Gynecomastia in men if estrogen is not controlled Unwanted hair growth

52 Follow Up to testosterone Replacement PSA every 6 months and DRE possibly Total and free testosterone levels initially in one or two months followed every 6 months. H and H DO NOT FORGET to check estradiol levels! Optimal blood levels 25 pg/g. Do not let levels get below 10 pg/g and preferably keep below 40pg/g. Do not be surprised but the average 55 year old man has a higher estradiol level than his 55 year old wife.

53 Treating Testicular Atrophy Can use HCG 250 units SQ on days 5 and 6 of testosterone cypionate WEEKLY cycle. Can use low dose SQ HCG 250 units daily

54 The AromataseEnzyme The enzyme responsible for conversion of testosterone to estradiol in a man. The enzyme becomes more active the older a man gets. 1 in 5 men are hyperaromatizers

55 Controlling Estrogen Excess in Men DIM- Diindolylmethane QD to BID Chrysin250mg bid PO or topical 50mg/g Zinc 50mg daily Progesterone 5-10mg transdermally Iodine/iodide 12.5mg weekly to daily Anastrozole 0.5mg 1 to 3 times a week or 0.25mg twice a week WARNING-do not let estrogen levels go too low in a man as they are required for brain, heart and bone functions.

58 How to Decrease SHBG Control estrogen excess Testosterone Stinging nettle Omega 3 s DHEA Vitamin D Avena sativa

59 Progesterone in Men Like testosterone it also enhances libido, improves mood, energy, improves muscle mass, stronger bones, helps keep weight down, stronger erections ect.. Helps in part to raise testosterone and lower estrogen Can help with man boobs Works together with testosterone It is a potent inhibitor of dihydrotestosterone(dht), a known cause of male pattern baldness and prostatic hyperplasia Antagonizes estrogen Topical over the counter progesterone cream USP at a dose of 5-10mg is usually adequate.

60 DHEA in Men Similar effects in men and women with deficiency. Despite thousands of studies worldwide no evidence of harm even at supraphysiologic doses. Produced mainly in the adrenal cortex but also secreted by the testes and brain. It serves as an androgen precursor and decline levels linked to lowered testosterone. Levels of 50mg or less daily generally restore normal DHEA levels. Replaced transdermaly, sublingually, or orally

61 Post-Presentation Questions

62 Progesterone deficiency symptoms include A. Mood swings and insomnia B. Endometriosis and excessive bleeding C. Bloating and water retention D. Headaches E. All of the above

63 T deficiency contributes to A. Obesity and insulin resistence B. Decreased libido C. Erectile dysfunction D. Depression E. All the above

64 The aromataseenzyme A. Converts estrogen to testosterone B. Converts testosterone to estrogen C. Neither

Accession #: Patient: Jane Doe Convert to pdf, Save or PRINT >> ADRENAL CHECK

Accession #: Patient: Jane Doe Convert to pdf, Save or PRINT >> ADRENAL CHECK Page 1 of 5 Patient: Jane Doe Tel: (123) 456-7890 Email: test@test.com Sex: Female Age: 36 yr Date of Birth: 1980-12-12 Height: 5 ft 0 in Weight: 135 lbs Waist size: 30 in 1st day of last menses: Day 07,