THYROID AND MENOPAUSE

THYROID AND MENOPAUSE DR. NISHIT F. SHAH M.D. ( Med ). D.M. ( Endo) CONSULTANT ENDOCRINOLOGIST P .D. HINDUJA NATIONAL HOSPITAL MAHIM, MUMBAI 400 016 THYROTROPES AND GONADOTROPES Pulse concordance TSH -- LH -- FSH -- Alpha subunit Men Postmenopausal women Hypothyroids [ Not euthyroid young women ] JCEM 1990; 71:425-32 THYROIDISMS AND GONADOTROPINS FSH IN POSTMENOPAUSAL HYPOTHYROIDS – 43% THYROTOXICS – 52% INHIBIN B  cycling women (Normal postmenopausal – 72%) Horm Metab Res. 2003; 35: 498-501 THYROTOXICS Basal LH higher Treatment increases FSH/LH ratio Br J Obstet Gynaec. 1977;84:254-7 THYROIDISMS AND EARLY MENOPAUSE HYPOTHYROIDISM CAUSING EARLY MENOPAUSE Lay websites : www.thyroid-info.com, www.womentowomen.com, www.thyroidtalk.com RADIOABLATION: I131 therapy for thyroid cancer Earlier menopause [ Median 49.5 v/s 51 years] JCEM 2001; 86: 3512-5 AUTOIMMUNITY : Premature Ovarian Failure Autoimmune oophritis Fert Steril. 2005; 83:1327-32 MENOPAUSE AND THYROID SURGICAL MENOPAUSE TSH to TRH : normalized with estrogens. Gynecol Endocrinol. 1993;7:279-83 CLIMATERIC SYNDROME 10% TSH TO TRH,  FT3,  FT4 Pituitary resistance to T4, T3 Normalized with L-T3 therapy. Acta Endocrinol. 1986; 111: 204-8 ESTROGEN EXPOSURE Early Menarche Late Menopause Hysterectomy (Hyperestrogenic state) Hashimoto’s Clin Endocrinol. 1990; 32:301-6 Thyrotoxicosis Minerva Chir. 1975;30:992-6 AGE OR MENOPAUSE The Colorado Thyroid Disease Prevalence Study Arch Intern Med 2000; 160: 526-34 AGE HYPOTHYROIDISM Overall 4 to 10% Elderly 7 to 26% 70% of all hypothyroids >50 years at diagnosis HYPERTHYROIDISM : Subclinical Overall 4% Elderly 6% More in iodine deficiency areas MENOPAUSE HEALTHY WOMEN STUDY TSH and antibody status (21% v/s 26%) did not differ by menopause status or HRT Ann Epidemiol.1995;5:229-33 SWAN: Study of Women’s Health Across the Nation TSH >5.0 in 6.2% TSH < 0.5 IN 3.2% No association with indicators of menopausal transition Clin Endocrinol. 2000; 58 : 340-7 MENOPAUSE CLINIC 1. Overt hypothyroid 2.6% Subclinical hypothyroid 8.6% Subclinical hyperthyroid 1.4% Clin Invest Med. 1995; 18: 11-8 2. Overt thyroidisms 2.4% Subclinical 23% 17% Hypothyroid 6% Hyperthyroid Climacteric 2002; 5 : 162 SCREENING FOR HYPOTHYROIDISM AT A MENOPAUSE CLINIC (in Thailand) Int J Gynaecol Obstet 2002;77: 39-40 n =1261  pre-, peri and post- menopausal TSH, FT4 HYPOTHYROIDISM 29.8% Overt 0.6% Subclinical 4.2% Secondary or tertiary 25% HYPERTHYROIDISM Thyrotoxic 0.3% Subclinical 1.3% HINDUJA HEALTH CHECK- UP: TSH TSH < 0.3 N ALL Jan1998-Dec1999 14715 n 382 % 2.6 n 1162 TSH > 5.0 % 7.9 SELECT Jan-Dec 2006 MALES 312 13 4 39 12 20-30 31- 40 41- 50 51+ FEMALES 20-30 31-40 41-50 51+ 21 62 110 119 819 57 138 296 328 1 3 4 5 52 4 3 14 31 5 5 4 4 6 7 2 8 9 6 7 10 16 130 7 25 38 60 29 11 9 13 16 12 18 13 18 SCREEN: ALL OR SELECT ? ALL : [ Vanderpump MP, Turnbridge WM Thyroid 2002; 12: 839-47] HYPERTHYROIDISM ( V/S PERIMENOPAUSE) Nervousness, Sweating, Palpitation, Insomnia, Weight loss, Diarrhea, Alopecia, Fractures. HYPOTHYROIDISM ( V/S POSTMENOPAUSE) Slowness, Memory loss, Lack of concentration, Depression* Cold intolerance, Dry skin, Brittle nails, Aches, Cramps, Paraesthesia, Constipation Hypothyroidism magnifies menopausal symptoms. *Depression correlates with TPO-Ab, not biochemical thyroid dysfunction or menopausal status JCEM 1998;83:3194-7 SUBCLINICAL HYPOTHYROIDISM SYMPTOMATIC RELIEF CARDIOVASCULAR RISK Hypothyroidism- Strong indicator for arteriosclerosis and myocardial infarction in elderly women Ann Intern Med. 2000;132: 270-8 Cardiac Function- Subtle impairment of myocardial contractility- diastolic dysfunction Cholesterol: Total, LDL, HDL Decrease in LDL by thyroxine therapy reduces cardiovascular risk by 9 to 31% JCEM 2001; 86:4860-6 T-Abs associated with  Lp ( a ) in men and postmenopausal women Eur J Endocrinol. 1997; 136:87-91 THYROXINE AND OSTEOPOROSIS L- Thyroxine prevents the beneficial effect of HRT on BMD Gynecol Endocrinol. 1999;13:196-201 NO OSTEOPOROSIS – Replacement therapy – Post Menopausal- slight  in QUS OSTEOPOROSIS – Replacement in ex-toxics, esp. post menopausal – Supressive therapy- cancer / benign goitre – Subclinical hyperthyroidism e.g. MNG. esp. post menopausal . Fractures. OSTEOPOROSIS PREVENTION Calcium supplementation: 1000 to 1500 mg/day. At least 4 hours after L-thyroxine. Vitamin D supplementation: 800 to 2000 units/day Antiresorptive drugs HRT ( including ex- toxics) Anti thyroid agents rhTSH- Reversible inhibition of bone resorption SUBCLINICAL HYPERTHYROIDISM Osteoporosis ( Hyperthyroidism 2.5 times more in fracture patients) Cardiac arrhythmia Thromboembolic complications Mortality from circulatory diseases  2 to 3 times Struma Ovarii : Post menopausal J Nucl Med. 1988;29:263-5 HYPOTHYROIDS ON ORAL HRT CEE 0.625 mg +/- MPA 5 mg12/30 NORMAL BASAL TBG T4 FT4 TSH TSH > 7 in 7/18 Arafah BM. NEJM 2001; 344: 1743-1749 THYROXINE REPLACEMENT BASAL 12 Weeks 12 Weeks 31.3+3.2 10.4+1.5 20.3+3.5 8.0+0.9 20.8+2.9 30.8+4.0 1.3+1.0 1.5+0.3 1.1+0.6 10.9+2.3 1.2+0.3 3.2+3.1 START/ STOPPAGE OF HRT: Reassess after 2 to 3 months HYPOTHYROIDS ON OTHER HRT TRANSDERMAL ET No effect on TBG RALOXIFENE No effect on TBG Co- administration:  TSH Thyroid 2001; 11:779-82 Reduced absorption of L- thyroxine Pharmacotherapy 2006; 26:881-5 SOY SUPPLEMENTS Decreased absorption of L- thyroxine TPO activity Goitrogen in iodine deficiency  Binding of T4 to Transthyretin Soy isoflavones do not adversely effect thyroid function in healthy, iodine replete postmenopausal women J Med Food 2003; 6: 309-16 THYROID NODULES AND CANCER BENIGN NODULES Slow growth after menopause J Endocrinol Invest. 2004; 27:31-6 THYROID CANCER Post Menopause OR 1.3 - natural OR 1.8 - artificial Early menarche, Late menopause Papillary Follicular [ Papillary have ER ] Premenopausal thyroid cancer  Risk of developing breast cancer RR 1.42 Cancer 2001; 92:225-31 BREAST CANCER IN POST MENOPAUSAL WOMEN • Hypothyroidism OR 3.8 • Low normal T4 OR 2.3 Thyroid 2005; 15:1253-9 • Thyroid disease 58% (v/s 18%) Subclinical hyperthyroidism 31% ERss positive Hypothyroidism 8% TPO-Ab 19%  TH/E2 ratio Braz J Med Biol Res. 2005; 38:761-5 •  Tumour size, Vascular invasion, metastatic LNs J Surg Oncol. 2004; 87:19-25 AN L-THYROXINE A DAY KEEPS THE DOCTOR AWAY