1. A novel non-estrogenic HRT in postmenopausal women with diabetes: DHEA supplementation Bharti Kalra, Sanjay Kalra

2. ADRENAL ANDROGEN PHYSIOLOGY cholesterol zona glomerulosapregnenolone aldosterone 100 mg/d zona fasciculata 17-OH pregnenolone cortisol 10mg/d zona reticularis DHEA androstened- >20mg/d 4mg 1.5mg DHEAS 7-15mg estradiol DHT

3. ACTH cortical androgen stimulating hormone (CASH) POMC derivatives joining peptide prolactin IGF- 1 cortisol DHEA androstenedioneage & gender related changes DHEA S no diurnal variation

4. AGE RELATED CHANGES Foetus birth Puberty peak old age Adrenarche 20-30gadrenopause 250 to 500 μ g/dl 25 μ g/dl

5. AIMS AND OBJECTIVES To assess the incidence of DHEAS deficiency amongst postmenopausal diabetic women with asthenia To assess the clinical correlates of DHEAS deficiency. To assess the effects of DHEA supplementation on asthenic symptoms in postmenopausal diabetic women.

6. STUDY DESIGN Prospective,open-label randomized study over 6 months Single centre study conducted from Oct 2005 to June 2006. 354 consecutive postmenopausal diabetic women complaining of asthenia were administered the Energy Fatigue Scale (Stanford). Women with positive score ( 2.20) underwent DHEAS estimation.

7. STUDY DESIGN Women with DHEAS levels below normal or in the lower quartile of normal range were randomized to either of 2 groups. Study group given DHEA supplementation 25 mg /day x 6 months along with routine medication; control given only antidiabetic drugs.

8. STUDY DESIGN Clinical and biochemical assessment was carried out at 3 months and 6 months. Dose of DHEA was adjusted at 3 months and 6 months according to DHEAS values. Aim to keep DHEAS values in upper half of normal range according to age

9. RESULTS 354 postmenopausal women with diabetes with asthenia. (diabetes 1-35 years; asthenia 1-24 months) 150 women with AADS (42.4%) STUDY GROUP: 75 DHEA Supplementation CONTROL GROUP: 75 No DHEA Supplementation

10. AGE DISTRIBUTION OF PATIENTS Age Yrs.31-4041-5051-6061-7071-8081-90 Study group 1 (1.3%) 27 (35.52) 32 (42.10%) 6 (7.89%) 5 (6.57%) 5 (6.57%) Control group 0 (0%) 32 (42.10%) 26 () 10 () 4 (%) 3 ()

11. AVERAGE DOSE/LEVELS OF DHEA The average dose of DHEA required to correct DHEAS levels was 24.31 ± 10.75 mg at 3 months and 30.40 ± 13.67 mg at 6 months. The average level at baseline was 40.86 ± 23.40 μg/ml in the AADS cohort. It rose to 81.39 ± 51.71 μg/ml at 3 months and 89.53 ± 51.50 μg/ml at 6 months

12. IMPROVEMENT IN ENERGY SCORE: Study group No. of subjects Drop- out zero 0.2- 0.8 1.0

13. CLINICAL CORRELATES OF ASTHENIC PATIENTS Frequency inAsthenic Patients (Total=354) DHEA-S deficient (AADS) patients (Total =150) Age > 60 Years*75 (21.18%) 79 (52.67%) Sensory neuropathy*186 (52.54%) 142 (94.66%) Motor neuropathy*79 (22.31%) 63 (42.00%) Albuminuria *19 (5.4%) 47 (31.33%) Chronic renal failure* (se creat >1.5) 14 (3.9%) 24 (16.00%) Hypothyroidism*75 (21.18%) 71 (47.33%) Poor glycemic control * (HB A1c >8.0%) 158 (44.64%) 95 (63.33%)

14. SIGNIFICANT CORRELATES

15. CLINICAL CORRELATES OF ASTHENIC PATIENTS Frequency inAsthenic Patients (Total=354) DHEA-S deficient (AADS) patients (Total =150) Hypertension288 (81.35%) 134 (89.33%) Coronary Heart disease5 (1.41%) 0 (0%) Stroke27 (7.62%) 15 (10. 00%) Foot Ulcer9 (2.54%) 0 (0%) Anemia130 (36.72%) 71 (47.33%) Hypoproteinemia18 (5.08%) 8 (5.33%) Hepatic Dysfunction28 (7.91%) 0 (0%)

16. EFFECTS DHEA-S levels rose significantly after supplementation with oral DHEA. Most patients felt the maximum benefit of therapy within 4-6 weeks. 16.00% study patients and 4.00% controls reported a subjective improvement in libido.

17. SIDE EFFECTS One patient each complained of excessive perspiration, itching, and increased anger, but there was no drop out. Symptoms were self-limiting in all patients. DHEA-S therapy is not associated with the side effects of estrogen therapy.

18. CONCLUSION Adrenal androgen deficiency (dehydroepiandrosterone sulfate [DHEAS] deficiency) is a common cause of asthenia (42 %) in postmenopausal women with diabetes

19. CONCLUSION DHEA supplementation is effective in 89.33%; and very effective in 76% of women with documented low or below average DHEAS.

20. CONCLUSION DHEA supplementation is well tolerated by postmenopausal women with diabetes. It is not associated with the side effects of estrogen therapy.

21. Sunsets are beautiful: our postmenopausal patients need not suffer unnecessarily

22. Thank you