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

A novel non-estrogenic HRT in postmenopausal women with diabetes:

DHEA supplementation

Bharti Kalra, Sanjay Kalra

ADRENAL ANDROGEN PHYSIOLOGY cholesterol

zona glomerulosa pregnenolone aldosterone 100 mg/d

zona fasciculata 17-OH pregnenolone cortisol 10mg/d

zona reticularis DHEA androstened- >20mg/d

4mg 1.5mg

DHEAS

7-15mg

estradiolDHT

ACTH cortical androgen stimulating hormone (CASH)

POMC derivatives

joining peptide

prolactin

IGF- 1cortisol DHEA

androstenedione age & gender

related changes

DHEA S

no diurnal variation

AGE RELATED CHANGES

Foetus birth

Puberty peak old ageAdrenarche 20-30gadrenopause

250 to 500 μ g/dl

25 μ g/dl

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.

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.

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.

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

RESULTS

354 postmenopausal women with diabetes with asthenia.

(diabetes 1-35 years; asthenia 1-24 months)

women with AADS (42.4%)

STUDY GROUP: 75

DHEA Supplementation

CONTROL GROUP: 75

No DHEA Supplementation

AGE DISTRIBUTION OF PATIENTS

Age Yrs. 31-40 41-50 51-60 61-70 71-80 81-90

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

()

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

IMPROVEMENT IN ENERGY SCORE: Study group

0

2

4

6

8

10

12

changein score

3 monthsfollow up

6 monthsfollow up

No. ofsubjects

Drop-out

zero 0.2-0.8

≥ 1.0

CLINICAL CORRELATES OF ASTHENIC PATIENTS

Frequency in Asthenic 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%)

SIGNIFICANT CORRELATES

0

10

20

30

40

50

60

70

80

90

100

age senN motN alb CRF thyr poorcontr

asthenia

AADS

CLINICAL CORRELATES OF ASTHENIC PATIENTS

Frequency in Asthenic Patients

(Total=354)

DHEA-S deficient (AADS) patients

(Total =150)

Hypertension 288

(81.35%)

134

(89.33%)

Coronary Heart disease 5

(1.41%)

0

(0%)

Stroke 27

(7.62%)

15

(10. 00%)

Foot Ulcer 9

(2.54%)

0

(0%)

Anemia 130

(36.72%)

71

(47.33%)

Hypoproteinemia 18

(5.08%)

8

(5.33%)

Hepatic Dysfunction 28

(7.91%)

0

(0%)

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.

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.

CONCLUSION

Adrenal androgen deficiency

(dehydroepiandrosterone sulfate [DHEAS]

deficiency) is a common cause of asthenia

(42 %) in postmenopausal women with

diabetes

CONCLUSION

DHEA supplementation is effective in

89.33%; and very effective in 76% of

women with documented low or below

average DHEAS.

CONCLUSION

DHEA supplementation is well tolerated by

postmenopausal women with diabetes. It

is not associated with the side effects of

estrogen therapy.

Sunsets are beautiful: our postmenopausal patients need not suffer unnecessarily

Thank you