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Hormone replacement therapy

Hormone replacement therapy

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Hormone replacement therapy

  1. 1. Hormone replacement therapy. What is new? BY Adeniji ADEKOGA 1
  2. 2. OUTLINE • Introduction • Histroy • Types of hormone replacement therapy • Transgender hormone replacement therapy • Testosterone hormone replacement therapy • Menopausal hormone replacement therapy • Conclusion • References 2
  3. 3. INTRODUCTION • Any form of medical treatment in which the patient re ceives hormones, either to supplement a lack of natura lly occurring hormones, or to substitute other hormon es for naturally occurring hormones. • The treatment replaces hormones that the body can no longer produce on its own due to age, damage or prem ature failure of reproductive organs. • Used primarily as a medical treatment for post-menopa use symptoms. It is also an effective solution for any in dividual suffering from hormone deficiencies, includin g men. 3
  4. 4. INTRODUCTION • About 6 million users of hormone replacement therapy (HR T) are in the USA and UK alone (CGESOC, 2015). The larg est geographical markets are the USA, France, Germany, Italy, Spain, UK and Japan (Lloyds, 2008). • There is poor awareness on the uses of HRT among Nigerian women (Nkwo, 2009a). Most Nigerian Gynaecologists prefer reassurance and anxiolytics for managing severe menopausal s ymptoms (Nkwo, 2009b). • Women with more than a high school education or whose ho usehold income was above the poverty level were more likely to use HRT than women with less education or lower family i ncome. 4
  5. 5. Histroy OF HRT Figure 1: History of HRT 5
  6. 6. Hormones Powerful chemical messengers. Derived from cholesterol. Made in the brain, ovaries, testicles, adrenal glan ds and body fat. Affect every tissue in the body. Overall effect depends on the balance between v arious hormones. Duration of exposure is as important as dose. 6
  7. 7. TYPES OF HRT • Human growth hormone (HGH) • Melatonin (pineal hormone) • T3 and T4 (thyroid hormones) • DHEA (dehydroepiandosterone) (adrenal horm one) • Pregnenolone (adrenal hormone) • Cortisol (adrenal hormone) • Estrogen (female sex hormone) • Progesterone (female sex hormone) • Testosterone (male and female sex hormone) 7
  8. 8. Transgender hormone replacement therapy • Introduction of hormones associated with the g ender that the patient identifies with (notably tes tosterone for trans men and estrogen for trans w omen). • Hermaphrodites may also receive HRT. • Cross-sex hormone treatment for transgender in dividuals is divided into two main types: – hormone replacement therapy (female-to-male). – hormone replacement therapy (male-to-female). (Moore,et al., 2003) 8
  9. 9. TABLE 1: Effects of hormonal treatment on transsexual people Male-to-female transsexual pe ople Female-to-male transsexual peopl e Positive effects Gynecomastia Deepened voice Enlarged areolae and nipple Hirsutism Decreased hair growth Clitoral growth, average 4–5 cm Softened skin Laryngeal prominence Reduced testicular volume Increased libido Decreased spontaneous erections Breast atrophy, histological Decreased libido Redistribution of fat Redistribution of fat Testosterone to male levels Calming effect Increased muscle mass Testosterone to female levels (Moore, et al., 2003) 9
  10. 10. TABLE 2: Effects of hormonal treatment on transsexual people Male-to-female transsexual p eople Female-to-male transsexual p eople Negative effects Venous thrombosis Acne Hyperprolactinemia Increased hematocrit Elevated liver enzymes Elevated liver enzymes Depression endometrial hyperplasia Decrease in hemoglobin Sleep apnea Prolactinoma Aggression and hypersexuality Breast cancer Poor lipid profile Prostatic carcinoma after orchiect omy Decreased insulin sensitivity Decreased insulin sensitivity Increased IGF Decreased IGF Decreased bone mineral density af ter gonadectomy Ovarian cancer (Moore, et al., 2003) 10
  11. 11. TESTOSTERONE replacement therapy Andropausal and ergogenic use. Primarily use as a potential replacement therapy for men with senile hypogonadism. It is also prescribed to lessen the effects or delay the onset of normal male aging. Used for men who have lost their testicular func tion to disease, cancer, or other causes. (Myers and Meacham,2003) 11
  12. 12. TESTOSTERONE REPLACEMENT THERAPY • Common goals of treatment are to re-establish sexual functioning, libido, and improve overall mood. • Restoration of normal testosterone levels can also imp rove muscle mass, prevent osteoporosis, maintain men tal acuity, and maintain virilization, especially in elderly males. • The presence of prostate cancer or male breast cancer is an absolute contraindication for testosterone replace ment treatment (TRT). (Morales, et al., 2000; Vermeulen, 2001; Myers and Meacham,2003) 12
  13. 13. Figure 2: Testosterone target organ 13
  14. 14. TESTOSTERONE REPLACEMENT THERAPY • TRT is recommended in men who have both: – low levels of testosterone in the blood (less than 300 ng/dl) – symptoms of low testosterone. • TRT is not recommended for men who have – prostate or breast cancer – a nodule on the prostate that can be felt during a DRE – a PSA greater than 3 ng/ml without further evaluation – a hematocrit greater than 50% or thick, viscous blood – untreated obstructive sleep apnea – severe lower urinary tract symptoms – class III or IV heart failure. 14
  15. 15. EFFECTS OF TRT a. BENIGN PROSTATIC HYPERPLASIA (BPH) TRT does not appear to grossly worsen Lower Urinary Tr act Symptoms (LUTS) and is not contraindicated in men diagnosed with BPH. The Saturation Model postulates th at the androgen receptors on the prostate are saturated at physiologic and even subphysiologic levels of testosteron e (Ohl and Quallich, 2006; Grech, et al., 2014). b. PROSTATE CANCER Prior literature has failed to definitively demonstrate an in creased risk in a cause-and-effect relationship between TR T and prostrate cancer. . Many longitudinal studies investi gating this relationship failed to find any association (Ohl and Quallich, 2006 ; Osterberg, et al., 2014). 15
  16. 16. EFFECTS OF TRT c. BREAST CANCER It has been suggested that high levels of testosterone may lead to increased aromatization to an active derivative of e strogen, which ultimately may stimulate breast tissue recep tors and increase the risk of male breast cancer (Ohl and Quallich, 2006; Grech, et al., 2014). d. Risk of Cardiovascular Morbidity and Mortality TRT increased serum erythropoietin, leading to erythrocyt osis or Polycythemia. This may lead to an increased incide nce of vascular events, including stroke, myocardial infarct ion and deep vein thrombosis with possible pulmonary em bolus (Osterberg, et al., 2014; Finkle, et al., 2014; Garnick, 2015). 16
  17. 17. EFFECTS OF TRT e. Impairment of Spermatogenesis Administration of exogenous testosterone interrupts the normal signaling of the Hypothalamic–pituitary–adrenal a xis (HPA), and will result in oligospermia or azoospermia that may not be reversible (Ohl and Quallich, 2006; Grec h, et al., 2014). f. Metabolic syndrome TST significantly improved symptoms of metabolic syndr ome associated with testosterone deficiency in men. Testo sterone increase insulin sensitivity in men with type 2 diab etes.(Endocrine Society, 2012, Hackett, et al., 2013; Fabian, et al., 2015 ). 17
  18. 18. EFFECTS OF TRT g. LIVER TOXICITY The risk for liver toxicity is highest with oral preparations, mode st with injections, and exceedingly low with the topical preparati ons (Ohl and Quallich, 2006). h. OBSTRUCTIVE SLEEP APNEA OSA is a risk associated with TRT in men, but its’ etiology is not particularly well understood. some studies suggested that there i s no association between OSA and TRT (Ohl and Quallich, 20 06; Grech, et al., 2014) i. FLUID RETENTION This side effect may be most pronounced in the frail or ill elderl y male, and generally resolves after the first few months of treat ment (Ohl and Quallich, 2006) 18
  19. 19. MENOPAUSAL HRT Menopause is a state of natural ovarian senescence with accompanying estrogen deficiency. It also refers to states of ovarian failure and ovarian destruction/removal with accompanying estrogen deficien cy (Amenorrhea for 1 year). CATEGORIES – Premature Menopause- refers to menopause in a woman aged below 40 years. – Early Menopause -refers to menopause in a woman aged 50 yea rs to 59 years. – Late Menopause -refers to menopause in a woman aged 60 year s and over. 19
  20. 20. MENOPAUSAL HRT CONTD • Surgical menopause- refers to menopause occurring as a result of surgical removal of both ovaries in a woman. • Medical menopause- refers to menopause occurring as a result of permanent damage to both ovaries in a woman fo llowing either chemotherapy or radiotherapy. • Menopausal transition: from the first features of approa ching menopause until up to 1 year after final menstrual p eriod. – Associated with significant hormonal variability over time – Overall, decline in oestrogen levels over the menopausal transitio n. (Freeman, et al., 2008) 20
  21. 21. MENOPAUSAL HRT CONTD Figure 3: signs and symptoms during the menopausal transition. Vasomotor Symptoms Sleep Disorders Mood Changes Urogenital Atrophy Dyspareunia Osteoporosis Atherosclerosis Coronary Heart Disease Cerebrovascular Disease 40 yrs 50 yrs Menopause 60 yrs Menstrual Disorders 21
  22. 22. Figure 4: Menopausal effects. 22
  23. 23. MENOPAUSAL HRT CONTD • Forms of Menopausal HRT • HT can be prescribed as local or systemic therap y. – Local preparations : Creams, Pessaries, Rings – Systemic formulations : Oral drugs, Transdermal pat ches and gels, Implants • PRODCUTS: – Estrogen alone – Combined estrogen and progestogen – Selective estrogen receptor modulator (SERM) – Gonadomimetics, such as tibolone, which contain estrogen, p rogestogen, and an androgen 23
  24. 24. MENOPAUSAL HRT CONTD • INDICATION: can be symptomatic or preventive. – Vasomotor symptoms – Urogenital symptoms – Osteoporosis • CONTRAINDICATION: – A history of breast cancer – A history of endometrial cancer (see Uterine Cancer and Endometrial Carcinoma) – Porphyria – Severe active liver disease – Hypertriglyceridemia – Thromboembolic disorders (see Deep Venous Thrombosis and Pulmonary Embolis m) – Undiagnosed vaginal bleeding (see Dysfunctional Uterine Bleeding) – Endometriosis – Fibroids 24
  25. 25. Uterus Sequential therapy without tablet break Regular bleeding at end of cycle MENOPAUSAL HRT CONTD Continuous Sequential HRT Estrogen Progestogen Day 14 Figure 5: schedule and forms of MHRT . Continuous Estrogen Estrogen No tablet break No bleeding as no uterus Uterus Continuous Combined HRT Estrogen Progestogen Day 14 Combined therapy without tablet break No bleeding at end of cycle 25
  26. 26. Benefits Relief of Menopause Symptoms Risks Breast Cancer Figure 6: MHRT risks and benefits
  27. 27. BENEFITS MHRT a. Vasomotor symptoms: – Hot flushes & night sweats resulting from hyperactivity of mid brain-hypothalamic-pituitary axis & characteristic of climacteric are relieved by HRT b. Sleep disturbances: – Early morning awakening and inability to get back to sle ep is a frequent complaint in postmenopausal women. E strogen receptors are present in Reticular Activation Syst em, preoptic area, and hypothalamus. Estrogen replacem ent improves sleep by acting at these sites. (Santen, et al ., 2010; De Villiers, et al.,2013) 27
  28. 28. BENEFITS MHRT c. Mood & psychological changes: – Estrogen replacement appears to have a direct mental to nic effect on the cognitive functions even in the absence of vasomotor symptoms .It over comes anxiety, over se nsitivity, tearfulness, irritability, aggression. However if progesterone is also given, it may reduce the beneficial e ffects of estrogen on libido & mood. d. Atrophy of genital tract – leading to vaginal dryness & postmenopausal bleeding fr om atrophic vaginitis / atrophic endometrium respond t o estrogen therapy. (Santen, et al., 2010; De Villiers, et al.,2013) 28
  29. 29. BENEFITS MHRT e. Dyspareunia – due to vaginal dryness is resolved with HRT. f. Loss of libido – also responds to estrogen replacement. Some also ge t benefit from testosterone. g. Skin, hair, body fat : – In postmenopausal women there is decrease in conte nt of collagen in skin .So the skin becomes wrinkled. Estrogen increases the collagen content .It also prev ents varicose ulceration. (Santen, et al., 2010; De Villiers, et al.,2013) 29
  30. 30. BENEFITS MHRT h. Urinary symptoms: – Incontinence –Urethral abnormality, Detrussor insta bility, Overflow Incontinence – Frequency, Urgency, Dysuria – Difficulty in voiding – Estrogen may produce considerable improvement i n these symptoms by increasing • Epithelial thickness, vascularity, closing pressure of urethr a • Adrenergic receptor in bladder urethral muscle • Collagen content of connective tissue (Santen, et al., 2010; De Villiers, et al.,2013) 30
  31. 31. BENEFITS MHRT i. Bone & skeleton: – Post menopausal women, due to increased bone res orption, exceeding the rate of new bone formation. Loose 30% of their total bone mass. It leads to oste oporosis, and fracture may occur with minimal / tri vial trauma. – Estrogens cause stimulation of C cells of thyroid res ulting in increased level of calcitonin, which causes i nhibition of osteoclastic bone resorption. – Progesterone has synergistic action, as it binds com petitively with glucocorticoid receptors in bone, thus inhibiting the resorbing effect of cortisone. (Santen, et al., 2010; De Villiers, et al.,2013) 31
  32. 32. BENEFITS MHRT j. Neuroprotection: – It reduces the risk of Alzheimer’s disease by reduci ng  amyloid protein & cholinergic dysfunction in brain. – It enhances the proliferation of neuronal cell popu lation within the hippocampus. – It regulates the synaptic neurotransmission & incr eases nerve growth factor. Thus it enhances neuro plasticity, memory, and cognition. – It delays the onset of Parkinson’s disease by its acti on on dopaminergic system in midbrain. 32
  33. 33. BENEFITS MHRT k. Cardiovascular system : – In menopause as there is increased level of plasma total ch olesterol & LDL and decreased level of HDL, leading to at herosclerosis, there is increase in cardiovascular diseases. – Estrogen causes decreases the incidence & mortality of I.H .D., due to its beneficial effect on the lipid metabolism. •Other benefits: – There is substantial decrease in the risk of fatal colon cance r. – There is reduction in age related macular degeneration, cata ract and severe nuclear sclerosis. – Less risk of Osteoarthritis (Santen, et al., 2010; De Villiers, et al.,2013) 33
  34. 34. RISKS OF MHRT • ENDOMETRIAL RISK: Continuous use of estrogen can cause endometrial hyperplasia, leading to endometrial carcinoma. Addit ion of progesterone reduces this risk as it : • inhibits DNA synthesis, • reduces the no. of estrogen receptors, • stimulates the enzyme 17alpha dehydrogenase, which converts E2 to E1. • BREAST NEOPLASIA: There is increased incidence of breast c arcinoma with long-term use of estrogen. – Progestogen has no protective effect . – So annual breast examination including mammography is n ecessary. (Million Women Study Collaborators,2005; Chlebowsk, et al., 2010) 34
  35. 35. RISKS OF MHRT • OVARIAN NEOPLASIA: Unopposed estrogen therap y may cause serous or endometrioid tumours in short o r long term use . So patients need annual pelvic examin ation (Collaborative Group on Epidemiological Studies of Ovarian Cancer,2015). • COLON CANCER: MHRT with estrogen plus a proge stogen decreases colon (Ritenbaugh, et al., 2008) • STROKE: Hormone use does not reduce stroke incide nce in older women with preexisting vascular disease (L obo, 2009; Henderson, et al., 2012). 35
  36. 36. RISKS OF MHRT • CORONARY HEART DISEASE: HRT use is not associated with an increase in risk of CHD when used in post-menopaus al women in< 10 years of menopause. There is increase in ris k of CHD in > 10 years of the menopause (Stevenson, et al., 2 009). • VENOUS THROMBOEMBOLIC DISEASE: MHT increase s the risk of venothrombotic episodes approximately 2-fold an d is multiplicative with baseline risk factors including age, high er body mass index, thrombophilias, surgery, and immobilizati on (Renoux , et al., 2010). • GALL BLADDER: Estrogen alone and estrogen plus a Proge stogen increase the risk of gallbladder disease (De Villiers, et al .,2013). 36
  37. 37. EMERGING CONCEPTS • Timing (window of opportunity) – Early start – Maintenance of estrogenic benefits • Patient selection – Avoiding generalized prescribing • Personalization – Tailoring dose to patient – Continuation and tapering the dose with age • Use of bio-identical hormone • Route of administration • Alternative therapy – Selective-receptor modulators (SERMSs), – Lifestyle , – Plant oestrogens (including soya and whole-grain cereal products)37
  38. 38. conclusion The benefits vs. the risks to the patient at both t he initiation of therapy and over time should be of utmost importance to the clinicians when co nsidering hormone replacement therapy. 38
  39. 39. REFERENCES • Chlebowski, R.T., Anderson, G.L., Gass, M., et al. (2010): Estrogen plus progestin and breast cance r incidence and mortality in postmenopausal women. JAMA, 3(04):1684–1692 • Collaborative Group on Epidemiological Studies of Ovarian Cancer (CGESOC) (2015): Menopaus al hormone use and ovarian cancer risk: individual participant meta-analysis of 52 epidemiological s tudies. Lancet, Published Online: http://dx.doi.org/10.1016/S0140-6736(14)61687-1doi:10.1371/j ournal.pone.0085805 • Fabian, U. A., Charles-Davies, M.A., Fasanmade, A.A, et al. (2015): Sex hormone and their relations hip with leptin and cardiovascular risk factors in pre and post-menopausal Nigerian women with m etabolic syndrome. CA, 3(3): 151-156. • Finkle, W.D., Greenland, S., Ridgeway, G.K., Adams, J.L., Frasco, M.A., et al. (2014): Increased risk of non-fatal myocardial infarction following testosterone therapy prescription in men. PLoS ONE 9(1):e85805. • Freeman, E.W., Sammel, M.D., Lin, H., Gracia, C.R., Kapoor, S. (2008): Symptoms in the menopau sal transition: hormone and behavioral correlates. Obstet Gynecol, 1 (11):127–136 • Garnick, M.B. (2015): Testosterone Replacement Therapy Faces FDA Scrutiny. JAMA, 313(6):563- 564. • Grech, M.D., Breck, J. and Heidelbaugh, J. (2014): Adverse Effects of Testosterone Replacement T herapy: An Update on the Evidence and Controversy. Ther Adv in Drug Safe, 5(5):10-200. • Hackett, G. (2014): Testosterone replacement therapy and cardiovascular events. BMJ, 2(349):g723 0. doi: 10.1136/bmj.g7230. 39
  40. 40. REFERENCES• Henderson, V.W. and Lobo, R.A. (2012): Hormone therapy and the risk of stroke: perspectives 1 0 years after the Women’s Health Initiative trials. Climacteric, 15:229 – 34 • Lobo, R.A. and Clarkson, T.B. (2011): Different mechanisms for benefit and risk of coronary he art disease and stroke in early postmenopausal women: a hypothetical explanation. Menopause, 1 8:237–240 • Million Women Study Collaborators (2005): Endometrial cancer and hormone replacement thera py in the Million Women Study. Lancet, 365:1543–1551 • Moore, E., Wisniewski, A., and Dobs, A. (2003): Endocrine treatment of transsexual people: a r eview of treatment regimens, outcomes, and adverse effects. Clin Endocrinol Metab, 88(8):3467 –3473 disease: a statement for healthcare professionals from the American heart association. Cir culation, 104: 499-503. • Morales, A., Bella, A.J., Chun, S., Lee, J., Assimakopoulos, P., Bebb, R., Gottesman, I., Alarie, P., Dugré, H., Elliott, S. A. (2010) : Practical guide to diagnosis, management and treatment of test osterone deficiency for Canadian physicians. Can Urol Assoc J., 4(4):269-275. • Mosca, L., Collins, P., Herrington, M.D., et al. (2001): Hormone replacement therapy and cardio vascular disease: A statement for healthcare professionals from the American heart association. Circulation, 104:499-503. • Myers, J. B., and Meacham, R. B. (2003): Androgen Replacement Therapy in the Aging Male. Re views in Urology, 5(4)216–226. • Nkwo, P. (2009a): Treatment preferences and awareness of hrt among Nigerian menopausal wo men. The internet journal of geriatrics and gerontology, 6(1). 40
  41. 41. REFERENCES • Nkwo, P. (2009b): Suboptimal management of severe menopausal symptoms by Nigerian gynaec ologists: a call for mandatory continuing medical education for physicians. Bmc women's health, doi:10.1186/1472-6874-9-30 • Osterberg, E. C., Bernie, A. M., and Ramasamy, R. (2014): Risks of testosterone replacement ther apy in men. Indian Journal of Urology, 30(1):2–7. • Renoux, C., D ell’Aniello, S., Suissa, S. (2010): Hormone replacement therapy and the risk of ven ous thromboembolism: a population-based study. J Thromb Haemost, 8:979–986 • Ritenbaugh, C., Stanford, J., Wu, L., et al. (2008): Conjugated equine estrogens and colorectal can cer incidence and survival: the Women’s Health Initiative randomized clinical trial. Cancer Epide miol Biomarkers Prev, 1(7):2609–2618 • Santen, R.J., Allred, D.C., Ardoin, S.P., et al. (2010): Executive summary: Postmenopausal hormon e therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab, 95(Suppl 1) : s1 – 66 • Stevenson, J.C., Hodis, H.N., Pickar, J.H., and Lobo, R.A. (2009): Coronary heart disease and men opause management: the swinging pendulum of HRT. Atherosclerosis, 2(07):336-340 • Vermeulen, A. J. (2001): Androgen replacement therapy in the aging male—a critical evaluation. J Clin Endocrinol Metab., 86(6): 2380-2390. 41
  42. 42. 42 THANK YOU FOR your devotion. 42

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