Hormone replacement therapy dr. sharda jain

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  • Tibolone ([7,17]-17-hydroxy-7-methyl-19-norpregn-5(10)-en-20-yn-3-one) is a hormone replacement therapeutic used in the treatment of climacteric complaints and the prevention of osteoporosis. Tibolone is a selective tissue oestrogenic activity regulator (STEAR). Tibolone substitutes for the loss of oestrogen production in postmenopausal women, and alleviates menopausal symptoms. Tibolone prevents bone loss following menopause or ovariectomy.
  • Following oral administration, tibolone is metabolized to three primary active agents: 3 α -hydroxy-tibolone; 3 β -hydroxy-tibolone; and Δ 4 -tibolone. The 3 α - and 3 β -OH-metabolites of tibolone bind solely to the estrogen receptors, resulting in estrogenic effects on the bone and vaginal tissue. The Δ 4 -isomer has affinity for the progesterone and androgen receptors. In endometrial tissue, the Δ 4 -isomer functions as a progestagen, whereas in the brain and liver it has androgenic effects. Bone Tibolone has a direct oestrogenic effect on bone, decreasing bone resorption and maintaining bone mass. Tibolone significantly improves bone mineral density (BMD), especially trabecular BMD. Endometrium Tibolone acts as an antioestrogen in the endometrium. Tibolone does not stimulate endometrial proliferation, and hence is associated with less vaginal bleeding (and less irregular bleeds) Mood and libido Tibolone may act indirectly to decrease sex hormone-binding globulin (SHBG) concentrations and thereby increase the availability of testosterone. Tibolone may therefore improve sexual function. Tibolone improves libido, possibly via weak androgenic activity in the central nervous system. Breast Tibolone and the Δ 4 -isomer have been shown to behave as progestins, decreasing the proliferation rate. Tibolone and its Δ 4 -isomer also stimulate apoptosis in breast cells. Tibolone also interferes with the metabolic pathways of estrogens in human breast cells. It strongly inhibits sulfatase activity and weakly inhibits 17 β -hydroxysteroid dehydrogenase activity, which result in blocking the conversion of estrone sulfate to estradiol; thereby encouraging the formation of biologically inactive oestrogen sulphate. Cardiovascular Effects Tibolone significantly reduces lipoprotein(a) and triglycerides, and modestly reduces low-density lipoprotein cholesterol. Other benefits include include stimulation of blood flow and vessel relaxation and an increase in fibrinolysis.
  • NOTES This randomized, open-label, parallel-group study compared the effect of continuous combined conjugated equine estrogens and medroxyprogesterone acetate (CEE/MPA) vs. tibolone on symptom control, vaginal bleeding, lipid profiles and tolerability. Apparently healthy postmenopausal women were randomly assigned CEE/MPA (0.625 mg/5.0 mg) or tibolone 2.5 mg daily for 13 treatment cycles, each of 28 days. In total 85 women received at least one dose of study medication, and of these 76 (89.4%) women completed the study (n = 40, CEE/MPA; n = 36, tibolone). The incidence of menopausal and urogenital symptoms decreased significantly over time in both treatment groups compared to baseline. Significant differences in symptom control (other than hot flushes) were observed between treatment groups in different cycles and for different symptoms, but no consistent or clinically significant trends were observed. No statistically significant differences in the incidence of vaginal bleeding were observed between treatment groups after cycle 4. Women treated with CEE/MPA or tibolone showed significant improvement of menopausal and urogenital symptoms, and sexual well being and had similar vaginal bleeding patterns after four cycles of therapy. CEE/MPA and tibolone each induced a different mix of changes in the circulating lipid profile. Reference 1. Baracat E. C., Barbosa I. C., Giordano M. G., Haidar M. A., Marinho R. M., Menegocci J.C., Morais K. M., Tomaz G. Wehba S. .A randomized, open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and Tolerability; Climacteric 2002; 5: 60-69.
  • Hormone replacement therapy dr. sharda jain

    1. 1. The Menopause Management Workshop Menopause H.R.T. Moderator :- DR. SHARDA JAIN
    2. 2. Dr. Sharda Jain MD(PGIMER), MNAMS, FICOG FIMSA, DHM,QM & AHO Director :- Sec General : Delhi Gynae Forum
    3. 3. How To Handle M E N O P A U S E
    4. 4. We all are Confused
    5. 5. In Last 15 years - this is my 15th presentation
    6. 6. PRESENTATION is an ART , Not a science . Which means It's Never perfect and can always improve.
    7. 7. Customer’s Place Most Unhappy Customer – learing
    8. 8. Put your self in a customer’s place Most unhappy customer are greatest source of learning
    9. 9. Menopause  Menopause marks the end of reproductive capacity of women and results from the permanent cessation of ovarian function  The median age for the onset of menopause: 51.4 years  Indian Context: 40.32–48.84 years  By 2015, about 130 million Indian women are expected to live beyond menopause Menopausal transition Xu J, et al. J Am Board Fam Pract. 2005;18:374–382. Umland ME. J Manag Care Pharm. 2008;14(3)(suppl S):S14–S19. Sharma S, et al. JK Sci. 2007;9(1):13–17. Aarti K. J Obst Gynecol India. 2011;323–326.
    10. 10. Menopause Long Term Effects Symptoms Vasomotor Urogenital Mood /Cognitive Osteoporosis Poor Bowel / Bladder Vision H. Dis. Skin M.Tone
    11. 11. Complaints % western women West India North India Irritability 92 48 36 Lethargy 88 45 - Depression 78 43 10 Flushes and night sweats 75 38 22 Headaches 64 27 15 Forgetfulness 61 60 65 Weight gain insomnia 51 60 70 How Common Are the various menopause symptoms
    12. 12. Relative frequency of climacteric Symptoms in India Symptoms India Incidence Anklesaria 1995 Krishna 1995 Hot Flashes 30% 33% Urinary Complaints 74% 35% Vaginal Symptoms 56% 50% Joint/ Muscle pain 20% 25% Psychological 36% 20%
    13. 13. Treatmentof Menopause after WHI is never the same
    14. 14. WHI Myths
    15. 15. Principles •Time – Shortest possible •Dose – Smallest possible •Counseling – All short & long term risks is mandatory of HT
    16. 16. Redefining TIBOLONE in menopause
    17. 17. Structure and Mechanism of Action  Tibolone is a selective tissue oestrogenic activity regulator.  Tibolone substitutes for the loss of oestrogen production in postmenopausal women, and alleviates menopausal symptoms.  Tibolone prevents bone loss following menopause or ovariectomy 1960/70 Steckelbroeck S, et al. Mol Pharmacol.2004;66: 1702–1711. Tibolone summary of product characteristics. Available at: www.medicines.org.uk.
    18. 18. Specific binding affinities of tibolone and its primary metabolites
    19. 19. Tissue-Specific Effects of Tibolone’s Metabolites Modelska K, et al. J Clin Endocrinol Metab. 2002;87(1):16–23. Palacios S. Eur Heart J Supplements. 2001; 3 (Suppl M): M12–M16. +: Stimulatory effect;-: Suppressive effect; ?: Unknown effect
    20. 20. Tissue-Specific Effects of Treatment Modalities for Menopause: The Tibolone Edge Tibolone Estrogen Estrogen+ progesterone Raloxifene (SERM) Bone (BMD) + + + + Climacteric symptoms + + + - Vagina + - - + Mood & libido ++ =/+ = = Endometrium = - - = Breast pain & density = - - = Breast cancer = - - =/+ Venous thromboembolism = - - - Myocardial infarction/stroke = - - = STEAR: Selective, tissue estrogenic activity regulator ; SERMs: Selective estrogen receptor modulator. +: Positive (beneficial effect); =: Neutral effect; -: Negative (detrimental) effect Kloosterboer HJ. J Steroid Biochem Mol Biol.2003;83: 157–165. The clinical profile of tibolone has advantages over other treatment modalities
    21. 21. Effect of Tibolone on Vasomotor and Urogenital Symptoms of Menopause
    22. 22. Summary of Comparison of Tibolone with Combine HT Assessment parameters Tibolone vs. estrogen+progesterone HT Vasomotor symptoms Comparable and significant reduction inhot flashes, sweating and vaginal dryness. Better improvement in dryness of skin with tibolone
    23. 23. Hot flushes: tibolone versus CHT (Comparable) Baracat et al.Climacteric 2002 Control of vasomotor symptoms *Significantly different from baseline; CEE, conjugated equine estrogens; MPA, medroxyprogesterone acetate Meanvalue 14 12 10 8 6 4 2 0 Baseline 3 6 9 13 * * * * * * * * Tibolone (n = 40) CEE/MPA (n = 45) Hot flushes Treatment cycle
    24. 24. Clinical Evidence 1: Tolerability Trial comparing Livial vs E2 / NETA Objective: To compare the efficacy and safety of tibolone vs. low-dose continuous combined estradiol plus norethisterone acetate (E2/NETA) in healthy symptomatic postmenopausal women (age: 45–65 years) (n=572). Study Endpoints: Prevalence of vaginal bleeding, hot flushes and adverse events. Study Results  Comparable reductions in vasomotor symptoms and vaginal atrophy in both the groups.  Significantly lower incidence of vaginal bleeding and breast pain/tenderness in the tibolone group. Conclusion: Tibolone produced effective and comparable reduction in menopausal symptoms, and was associated with a lower incidence of vaginal bleeding and breast pain/tenderness vs. E2/NETA. Hammar ML, et al. BJOG. 2007;114(12):1522–1529.
    25. 25. Tibolone V/S HT Urogenital symptoms Significantly lower incidence and recurrence of vaginal bleeding/spotting Significant improvement of lower vaginal tract symptoms Improvement in vaginal cytology
    26. 26. Clinical Evidence 2: Long-Term Effects of Tibolone on Urogenital Symptoms Objective: To evaluate the effects of six years of tibolone therapy on the genital tract in postmenopausal women (n=113). Study Endpoints: Assessment of urogenital symptoms, vaginal epithelial activity and calculation of vaginal karyopyknotic index and maturation index. Study Results  Significant improvement in the lower genital tract symptoms in comparison to control.  Significant increase in the karyopyknotic index and maturation index in the tibolone group.  Improvement in vaginal symptomatology with minimal endometrial stimulation. Conclusion: Tibolone was effective at maintaining an inactive endometrium while providing oestrogenisation of the lower genital tract. Morris EP, et al. Br J Obstet Gynaecol. 1999;106(9):954–959.
    27. 27. Assessment parameters Tibolone vs. Estrogen+progesterone (E+P) Raloxifene Bone Significantly greater increase in lumbar spine, trochanter and total hip BMD with tibolone Significantly greater increase in lumbar spine and total hip BMD with tibolone Tibolone V/S HT (E + P) & Raloxifene BONE
    28. 28. Clinical Evidence 1: Study of Tibolone V/s raloxifene Effects on osteoPenia (STEP) Objective: To compare the efficacy of tibolone vs. raloxifene on BMD of the lumbar spine and hip in osteopenic postmenopausal women (n=308). Endpoints: Measurement of BMD, serum osteocalcin and serum type I collagen C-telopeptides Study Results  Larger increase in lumbar spine BMD after 1- and 2- years and total hip BMD after 2 years of therapy with tibolone vs. raloxifene.  Comparable reductions in serum osteocalcin and serum type I collagen C-telopeptides . Conclusion: Tibolone prevented postmenopausal bone loss in older women and resulted in a larger increase of BMD both at the lumbar spine and hip than raloxifene Delmas PD, et al. Osteoporos Int. 2008;19(8):1153– 1160. Tibolone vs. raloxifene p<0.01 for lumbar BMD (1 y) p<0.001 for lumbar BMD (2 y) p<0.05 for total hip BMD (2 y)
    29. 29. Clinical Evidence 2: Long-term Intervention on Fractures with Tibolone (LIFT) Objective: To assess the efficacy of tibolone in preventing bone loss and its effects on fractures, breast cancer and cardiovascular disease. Endpoints: Assessment of vertebral fractures and rates of cardiovascular disease and breast cancer. Study Results  Increase in BMD of the spine and femoral neck in the tibolone group.  Decreased risk of vertebral and non-vertebral fractures with tibolone.  Decreased risk of invasive breast cancer and colon cancer with tibolone therapy.  Increased risk of stroke, but no difference in the risk of coronary heart disease or venous thromboembolism with tibolone vs. placebo. Conclusion: Tibolone reduced the risk of fracture and breast cancer and possibly colon cancer in older women with osteoporosis. B Cummings SR, et al. N Engl J Med. 2008;359(7):697–708.
    30. 30. Summary of Effects of Tibolone V/S HRT SEXUAL HEALTH Improvement in sexual health and loss of libido Increased sexual frequency, satisfaction and enjoyment Significant reduction in SHBG Increase in free testosterone levels MOOD Improvement in mood
    31. 31. Clinical Evidence 2: Efficacy of Tibolone vs. Conventional HRT on Sexual Function Objective: To compare the effects of TIBOLONE VS. CONVENTIONAL HORMONE REPLACEMENT THERAPY on climacteric symptoms and sexual function in postmenopausal women (n=140). Endpoints: Evaluation of the GCS questionnaire and Rosen's FSFI. Measurement of SHBG, FEI and FTI. Follow-up period: 6 months. Study Results  Comparable improvement in climacteric symptoms.  Greater improvement in the sexual subscore of GCS in the tibolone group.  Greater improvement in the desire, arousal and orgasm sexual domains of the FSFI in the tibolone group  Greater and significant reduction in SHBG and increase in FEI and FTI in the tibolone group. Conclusion: Tibolone was found to be an effective alternative to conventional HRT in the treatment of climacteric symptoms and sexual dysfunction in postmenopausal women. Ziaei S, et al. Climacteric. 2010;13(2):147–156. p<0.001 for tibolone vs. CEE/MPA and control
    32. 32. ENDOMETRIUM NO DIFFERENCE IN THE INCIDENCE OF PROLIFERATION, ENDOMETRIAL HYPERPLASIA OR CANCER MORE FREQUENT AMENORRHEA WITH TIBOLONE Summary of Comparison of Tibolone with HRT ( E2/ NETA)
    33. 33. Clinical Evidence 1: Tibolone v/S HRT Histology on the Endometrium and Breast Endpoints Study (THEBES) Objective: To compare the endometrial safety of tibolone vs. CEE/MPA in healthy postmenopausal women (n=3240) Endpoints: Evaluation of the incidence of abnormal endometrial histology (hyperplasia or carcinoma) and hyperplasia and carcinoma after 1 and 2 years of treatment. Study Results  No endometrial hyperplasia in the tibolone group.  More frequent amenorrhea was reported with tibolone 1.25 mg (78.7%) and 2.5 mg (71.4%) than CEE/MPA (44.9%).  Low incidence of breast pain in the tibolone group. Conclusion: Tibolone did not induce endometrial hyperplasia or carcinoma in post-menopausal women, and was associated with a better vaginal bleeding profile than CEE/MPA. Archer DF, et al. J Clin Endocrinol Metab. 2007;92(3):911–918.
    34. 34. Key Take Home Messages— Tibolone Breast Cancer Breast Cancer Effective in symptomatic breast cancer patients, with improvement in quality of life*
    35. 35. Tibolone & Breast pain and density Breast pain & density Lower incidence/decrease in breast pain/tenderness/mastalgia No increase in mammographic density of breast Decrease in breast density scores Decreased expression of immunohistochemical markers
    36. 36. Tibolone Does Not Increase the Mammographic Breast Density Lundström E, et al. Am J Obstet Gynecol. 2002;186(4):717–722.
    37. 37. Clinical Evidence: Tibolone vs. 17β-Estradiol in SURGICAL MENOPAUSE Objective: To compare the effectiveness of tibolone and 17β-estradiol on climacteric symptoms in surgically menopausal women (n=40) Endpoints: Assessment of climacteric symptoms with Greene Climacteric Scale at baseline, during washout and after the treatments. Study Results  Significant improvement from baseline in all the subscale scores in both study groups.  Improvement in psychological, somatic and sexual subscales was significantly superior in the tibolone group.  Comparable relief of vasomotor symptoms in both groups Conclusion: Tibolone may improve mood, libido and somatic symptoms in surgically menopausal women to a greater extent than estrogen therapy alone. Somunkiran A, et al. Maturitas. 2007;56(1):61–68.
    38. 38. Clinical Evidence: Effect of Tibolone on Health-Related Quality of Life Objective: To assess the improvements in HRQOL in menopausal women using tibolone (n=100). Endpoints: Assessment of change in HRQOL after 3 and 12 months of treatment. Study Results  Significant improvement in HRQOL after 3 and 12 months of treatment with tibolone.  Maximal improvement was observed in the somatovegetative subscale. Conclusion: Tibolone was found to be effective in improving the overall HRQOL of menopausal women. Somatovegetative symptoms showed most improvement. Bhattacharya SM. Int J Gynaecol Obstet. 2007;99(1):43–45. Somatoveget ative complaints Psycholo gical complain ts Urogenita l complaint s Baseline 9.9 12.2 7 After 3 months 5.3 5 2.9 After 12 months 3.8 4.4 2.4
    39. 39. Golden Tips
    40. 40. Huang K-E, et al. Climacteric. 2010;13:317–327. Key Take Home Messages— Summary of Effects of Tibolone Assessment parameters Summary of effects of tibolone Vasomotor symptoms Significant and effective reduction in vasomotor symptoms (hot flushes, vaginal dryness, sweating, and dryness of skin) Urogenital symptoms Significantly lower incidence and recurrence of vaginal bleeding/spotting Significant improvement of lower vaginal tract symptoms Improvement in vaginal cytology Sexual health Improvement in sexual health and loss of libido Increased sexual frequency, satisfaction and enjoyment Significant reduction in SHBG Increase in free testosterone levels Mood Improvement in mood
    41. 41. Key Take Home Messages— Comparison of Tibolone with other Therapy Options Assessment parameters Tibolone vs. Estrogen+progesterone (E+P) Raloxifene Bone Significantly greater increase in lumbar spine, trochanter and total hip BMD with tibolone Significantly greater increase in lumbar spine and total hip BMD with tibolone Endometrium No difference in the incidence of proliferation, endometrial hyperplasia or cancer More frequent amenorrhea with tibolone - Breast pain and Density Significantly lower incidence of breast pain/tenderness/mastalgia with tibolone Greater increase in mammographic breast density with E+P Decrease in breast density score with tibolone vs. increase with E+P Decreased expression of immunohistochemical markers with tibolone
    42. 42. Be Passionate and Exciting Excitement is contagious- just like a Yawn
    43. 43. A Mediocre person tells. A good persons explains A superior person demonstrates A great person inspires others to see & makeup their mind for themselves Harvey Mackey
    44. 44. Be Clear And Direct
    45. 45. SURGICAL MENOPAUSE • Livial • Miniasprin • Esosteo Recurrent Vag / UTI • Livial • Rule out DM • Neuro Dermatitis • Local Oest. cream Moderate to severe Dyspareunia • Livial • Local estrogen • Counseling of Couple
    46. 46. Answer Question Directly And clearly If you are asked a question and you give a “POLITICIAN’S ANSWERS” – in other words, if You Don’t answer the question – your credibility will decline,
    47. 47. Thank You
    48. 48. Hope Some Clarity is There !!
    49. 49. ADDRESS 35 , Defence Enclave, Opp. Preet Vihar Petrol Pump, Metro pillar no. 88, Vikas Marg , Delhi – 110092 CONTACT US 011-22414049, 42401339 WEBSITE : www.lifecarecentre.in www.drshardajain.com www.lifecareivf.com E-MAIL ID Sharda.lifecare@gmail.com Lifecarecentre21@gmail.com info@lifecareivf.com &

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