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How to Reverse the Aging of the Face Thierry Hertoghe, MD

How to Reverse the Aging of the Face Thierry Hertoghe, MD. To teach physicians How to detect the hormone deficits behind the aging of the face and distinguish them from each other through a better knowledge of their different physical signs

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How to Reverse the Aging of the Face Thierry Hertoghe, MD

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  1. How to Reverse • the Aging • of the • Face • Thierry Hertoghe, MD

  2. To teach physicians How to detect the hormone deficits behind the aging of the face and distinguish them from each other through a better knowledge of their different physical signs Provide an insight into the scientificstudiesthat show the relationshipsbetween hormone deficits and tissue (including facial) aging Which hormone treatmentscorrect these hormone deficits and, thereby, reduce or even reverse the aging of the face Practicaltipsfor improving hormone treatmentefficacy and tolerance Learning objectives? Make the body firm, increase lean mass (muscles, skin, inner organs)

  3. People’s face ages ……… Unnecessarily!

  4. New, well-kept house = Age 30, untreated = Age 65, untreated House not well cared of, not repaired

  5. = Untreated veryoldperson, 75-80 Ruin

  6. How can we partially or even near totally reverse the aging of the face? = Future Age 75, starts hormone & peptide therapies Age 78, hormone & peptide treated Age 80, treated = Age 83, treated Age 85 => Outlook of a age30? House not well cared of, not repaired New, well-kept house Young looks = healhty

  7. NEW In 20 years, wewillbe able to reverse aging completely. This book is the first step to it, a major step.

  8. Reversing Physical Aging, Volume 1

  9. Reversing • theAging • of the Face

  10. Aging faces: The changes

  11. + Hormone treatment review tables

  12. Whatmakes a young face attractive? Pyramide of age Triangle of youth

  13. Whatmakes a young face attractive? Triangle of youth Pyramide of age

  14. What ages in the face: Overview

  15. Aging faces: Hormone deficiencies MSH, melatonin, & IGF-1 deficiencies Estrogendeficiency Vasopressindeficiency Testosteronedeficiency GH & IGF-1 deficiencies

  16. ReversingGlobally Aging Faces

  17. Globally aging faceof growth hormone-deficiency

  18. AdultGrowth Hormone Deficiency Atrophy Droopiness Thinning of hair Thinning of eyebrows Droopy eyelids Deep wrinkles Sagging cheeks

  19. Thin, sparseeyebrows  IGF-1, GH  Testosterone Middle third Inner third Outer third  Thyroid

  20. GH treatment: effect on GH-deficient face

  21. 1 yr of hGH => sign.  skin thickness, elastic fibres, blood vessels  SUBJECTS: 5 patients + osteoporosis => human GH for REPORT: 1 year of hGH => skin changes by light & electron microscopy: The abnormally thin skin of osteoporosis => changed towards normal consistent proliferation of blood vessels  number of mast cells & fibrocytes The collagen bundles & elastic tissue fibers appeared hyperplastic & more horizontally oriented. restored to a normal configuration of the fine, vertical elastic fibrils of the papillary dermis had appeared decreased before treatment CCL:Since there was no evidence of stimulation of hair, sebum, or melanin such as occurs in acromegaly, it appears that the direct action of hGH on the skin is limited to mesenchymal structures. Aloia JF, Grover RW. Dermal changes in osteoporosis following prolonged treatment with human growth hormone. J CutanPathol. 1976;3(5):222-31

  22. Growth hormone treatment clearly reduces wrinkled faces

  23. Growth hormone treatment => Reverses facial aging Frequency (% patients with (unimproved) sign) Cheek ptosis Deeply wrinkled face Eyelid ptosis Skin ptosis under chin 94% 85% 85% 83% 31% 29% 23% 25% n = 48 adult patients Hertoghe T. Growth hormone itherapy in aging adults. Anti-aging Med Ther. 1997; 1:10-28

  24.        GH => FACE:  soft tissue,  lipoatropy in HIV • SUBJECTS:25 HIV-1 patients + moderate to severe facial lipoatrophy => on antiretroviral treatment for > 18 months => rhGH (5 mg) every other day for 6 months. After treatment was completed => participants => followed up for 6 months • RESULTS: Nearly all participants (24 of 25) completed the study. • Sum of bilateral soft tissue thickness at level of zygomatics at months 0, 3, 6, 12 => +19% successively 7.23, 8.59, 8.35,8.60 mm at CT scan • Sign. improvement from baseline in month 3 (p=0.009) & month 12 (p=0.021). • In the 6 months of follow-up & stop of GH =>no sign.  of soft tissue • Several side effects incl. diarrhea, arthralgia, myalgia, mastalgia & hand numbness => self-limited and transient. Honda M, Yogi A, Ishizuka N, Genka I, Gatanaga H, Teruya K, Tachikawa N, Kikuchi Y, Oka S. Effectiveness of subcutaneous growth hormone in HIV-1 patients with moderate to severe facial lipoatrophy. Intern Med. 2007;46(7):359-62

  25. Growth hormone Treatment

  26. For GH deficiency The best treatment = bioidenticalgrowth hormone = chain of 191 aminoacids Doses: 0.05-0.4 mg/day NOTE: Be sure thereis no untreated cortisol deficiency

  27. TIP1: How to inject? Extend the skin No skin pinching

  28. TIP 2: Where to inject ?Often on externalthigh & abdomen

  29. TIP 3: When to inject ? • At bedtime • At bedtime NIGHT Serum Growth Hormone Levels (circadianrhythm) NIGHT DAY DAY

  30. TIP 4: Graduallyincrease the GH dose Growth hormone ….…………….0.05 mg/dayduring 10 -14 days Then ……………..0.010 mg/dayduring 10 -14 days Thenfollow-up consultation after 3 months of treatment Then……………..0.015 mg/dayduring 10 -14 days Then……………..0.20 mg/dayduring 10 -14 days, etc. Usual dose between 0.10 and 0.35 mg/day

  31. Reason to increase GH progressively, stepafterstep: GH reduces cortisol production & activity! => RISK: ADRENAL DEFICIENCY!

  32.  thyroid & androgenactivities, GH => cortisol activity Cortisol production at 2-6 PM Urinary cortisol metabolites Plasma peak cortisol afterintake Change (% of initial levels) -21% -22% Study 2 (1 year): 14 GH-deficient men -43% Study 3 (6 months): 9 GH-deficient men Study 1 (7 days): 8 healthy men Persistent cortisol activity In healthy & GH-deficient men VierhapperH, Nowotny P, Waldhausl W. Treatment with growth hormone suppresses cortisol production in man. Metabolism 1998 Nov;47(11):1376-8 ; Rodriguez-ArnaoJ, Perry L, Besser GM, Ross RJ. Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy. ClinEndocrinol (Oxf) 1996 Jul;45(1):33-7 ; Weaver JU, Thaventhiran L, Noonan K, Burrin JM, Taylor NF, Norman MR, Monson JP. The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults. ClinEndocrinol (Oxf) 1994 Nov;41(5):639-48 ; • 4) Carani C, Granata AR, De Rosa M, Garau C, Zarrilli S, Paesano L, Colao A, Marrama P, Lombardi G.The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency. Eur J Endocrinol 1999 Mar;140(3):224-30 ; 5) Belgorosky A, Martinez A, Domene H, Heinrich JJ, Bergada C, Rivarola MA .High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment. : J ClinEndocrinolMetab 1987 Dec;65(6):1107-11

  33. Avoidadrenaldeficiencyduring GH treatment Check beforehandadrenalfunction (serum, saliva, 24h urine): If cortisol levels are borderline low (in lowertertile) Treat the CORTISOL DEFICIENCY! with hydrocortisone (bio-identical) or one of itssyntheticderivatives) at physiological doses under protection of a DHEA supplement

  34. TIP 5: Graduallyincrease the dose in thyroid-treated patients Growth hormone …………….0.05 mg/dayduring 10 -14 days Then ……………..0.010 mg/dayduring 10 -14 days Thenfollow-up consultation after 3 months of treatment Then……………..0.015 mg/dayduring 10 -14 days Then……………..0.20 mg/dayduring 10 -14 days, etc. Usual dose between0.10 and 0.35 mg/day

  35. Reason to increase GH progressively, stepafterstep, in thyroid-treated patients: GH =>  conversion of T4 into the very active T3 => RISK: T3-HYPERTHROIDISM!

  36.  thyroid & androgenactivities, GH =>  conversion of T4 to T3 GH treatment n = 14 GH-deficientadults UPPER REF. LIMIT Before +30% Average Serum T3 (3,2-6,5 pmol/L) LOWER REF. LIMIT P < 0.01 Rodriguez-ArnaoJ, Perry L, Besser GM, Ross RJ. Growth hormone treatment in hypopituitary GH deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy. ClinEndocrinol (Oxf) 1996 Jul;45(1):33-7 • 4) Carani C, Granata AR, De Rosa M, Garau C, Zarrilli S, Paesano L, Colao A, Marrama P, Lombardi G.The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency. Eur J Endocrinol 1999 Mar;140(3):224-30 ; 5) Belgorosky A, Martinez A, Domene H, Heinrich JJ, Bergada C, Rivarola MA .High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment. : J ClinEndocrinolMetab 1987 Dec;65(6):1107-11

  37. TIP 6: GH therapyincreasesandrogenactivity=> mayrequire a reduction in androgen doseif the patient istakingandrogentherapy

  38. GH => Androgenactivity Testosteronestimulated by HCG  Bioavailabletestosterone +25% SHBG Change (% of initial levels) -32% • 4) Carani C, Granata AR, De Rosa M, Garau C, Zarrilli S, Paesano L, Colao A, Marrama P, Lombardi G.The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency. Eur J Endocrinol 1999 Mar;140(3):224-30 ; • 5) Belgorosky A, Martinez A, Domene H, Heinrich JJ, Bergada C, Rivarola MA .High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment. : J ClinEndocrinolMetab 1987 Dec;65(6):1107-11

  39. IGF-1Treatment

  40. For aging faces due to IGF-1 deficiency The best treatment bioidentical IGF-1 (Or non-bioidentical longacting IGF-1) Doses: 0.2-0.5 mg/day Doses: 0.02-0.05 mg/day

  41. TIP 1: Where to inject IGF-1?Same places as GH:often on externalthigh & abdomen

  42. TIP 2: in most cases, no gradualincreaseof the IGF-1 dose isnecessary Usualstarting IGF-1 dose = 0.3 mg/day (long-acting IGF-1: 0.03mg/day) Usual final dose between 0.2 and 0.7 mg/day Usualstarting long-acting (R3) IGF-1 dose = 0.03 mg/day (long-acting IGF-1: 0.03mg/day) Usual final dose between 0.02 and 0.1 mg/day (long-acting IGF-1 (R3): 0.02-0.1mg/day)

  43. Reason: NO risk of adrenaldeficiencyduring IGF-1 treatment IGF-1 =>  transformation of stem cells of adrenal glands intocortisol-producingcell  cortisol production & levels

  44. TIP 3: In thyroid-treatedpatients, a gradualincrease of the IGF-1 dose isnecessary IGF-1 ….…………….0.1 mg/dayduring 10 -14 days Then …………….. 0.2 mg/dayduring 10 -14 days Thenfollow-up consultation after 3 months of treatment Then……………..0.3 mg/day, etc. Usual dose between 0.2 and 0.7 mg/day NOTE: For Long-acting (R3) IGF-1: 10x lower dose

  45. Reason to increase IGF-1progressively, stepafterstep, in thyroid-treated patients: IGF-1 =>  conversion of T4 into the very active T3 => RISK: T3-HYPERTHROIDISM!

  46.  thyroid & androgenactivities, IGF-1 =>  conversion of T4 to T3 in 8 healthyindividuals IGF-1 treatment  thyroidactivity +19% UPPER REF. LIMII Serum free T3 (pmol/L) Saline Serum TSH (0.4-4.5) mIU/ml) + 19% Mean Saline treatment IGF-1 treatment LOWER REF. LIMIT - 44% Healthy adults Thyrotropin was reduced significantly during IGF-I treatment and FT3 levels rose significantly (Fig. 1), Fig. 2. Free triiodothyronine levels in GH-deficient subjects during control (C), GH, IGF-I and combined GH+IGF-I treatment. For details, see text (meansiso, ANOVA for repeated measures). Figure: Ssign. (p<0.05) increases free T3, reduction of TSH, but no change of total T3, rT3, total & free T4 in 8 healthyindivudals on day 5 of IGF-1 treatment (10µg/kg/hr Hussain MA, Schmitz O, Jorgensen JO, Christiansen JS, Weeke J, Schmid C, Froesch ER. Insulin-like growth factor I alters peripheral thyroid hormone metabolism in humans: comparison with growth hormone. Eur J Endocrinol. 1996 May;134(5):563-7. PubMed PMID: 8664976. • 4) Carani C, Granata AR, De Rosa M, Garau C, Zarrilli S, Paesano L, Colao A, Marrama P, Lombardi G.The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency. Eur J Endocrinol 1999 Mar;140(3):224-30 ; 5) Belgorosky A, Martinez A, Domene H, Heinrich JJ, Bergada C, Rivarola MA .High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment. : J ClinEndocrinolMetab 1987 Dec;65(6):1107-11

  47. TIP 4: GH & IGF-1 therapies => Synergistically stimulating effects on thyroidfunction

  48.  thyroid & androgenactivities, After 5 daysGH + IGF-1 =>  conversion of T4 to T3 GH + IGF-1 2 IU/m²/day UPPER REF. LIMIT +19% After 5 days +19% +88% GH Serum free T3 (pmol/L) +39% IGF-1 7.5 Average Saline Control +11% 6.1 4.9 4.4 LOWER REF. LIMIT 4.4 Healthy adults Thyrotropin was reduced significantly during IGF-I treatment and FT3 levels rose significantly (Fig. 1), Fig. 2. Free triiodothyronine levels in GH-deficient subjects during control (C), GH, IGF-I and combined GH+IGF-I treatment. For details, see text (meansiso, ANOVA for repeated measures). Figure: Higher free T3,  total T3,slight rT3 under GH & GH + IGF-1, but no change of total & free T4 in 8 GH- & TSH-deficientindividualson day 5 of treatment Hussain MA, Schmitz O, Jorgensen JO, Christiansen JS, Weeke J, Schmid C, Froesch ER. Insulin-like growth factor I alters peripheral thyroid hormone metabolism in humans: comparison with growth hormone. Eur J Endocrinol. 1996 May;134(5):563-7. • 4) Carani C, Granata AR, De Rosa M, Garau C, Zarrilli S, Paesano L, Colao A, Marrama P, Lombardi G.The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency. Eur J Endocrinol 1999 Mar;140(3):224-30 ; 5) Belgorosky A, Martinez A, Domene H, Heinrich JJ, Bergada C, Rivarola MA .High serum sex hormone-binding globulin (SHBG) and low serum non-SHBG-bound testosterone in boys with idiopathic hypopituitarism: effect of recombinant human growth hormone treatment. : J ClinEndocrinolMetab 1987 Dec;65(6):1107-11

  49. Differenteffects of GH & IGF-1Treatmenton the face

  50. GH therapy is more efficient than IGF-1 on the face: GH =>  T3 betterthan IGF-1 • GH slims more • => Fatty faces • Facial fatness • GH tightensbetter • => Lax faces • Eyelid ptosis Large wrinkles • Elasticity, looseskin • Cheek ptosis • Skin ptosis under the chin

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