1. DHEA- WONDER DRUG?
DR.SATHYA BALASUBRAMANYAM
MD,DNB,MRCOG,FNB(REPROD MED)
INSTITUTE OF REPRODUCTIVE MEDICINE
AND WOMEN’S HEALTH, MADRAS MEDICAL
MISSION, CHENNAI

2.  What is DHEA?
 History of use in poor responders
 Review of literature
 Our experience in IRM&WH
 Conclusions

3. What is DHEA?
 DHEA is an important endogenous steroid
hormone.
 It is the most abundant circulating steroid in
humans.
 It is produced in the adrenal glands, the gonads, and
the brain, where it functions predominantly as
a metabolic intermediate in the biosynthesis of
the androgens and estrogens.

4. Place in the steroid synthetic pathway.
 Cholesterol--- Pregnenolone---17 alpha
Pregnenolone----DHEA---- Androgens---- Estrogens

5. Are DHEA and DHEAS different?
 DHEAS is the sulfate ester of DHEA. This conversion
is reversibly catalyzed by sulpho transferase
primarily in the adrenals, the liver, and small
intestine.

6.  In the blood, most DHEA is found as DHEAS with
levels that are about 300 times higher than those of
free DHEA.
 Orally ingested DHEA is converted to its sulfate
when passing through intestines and liver.

7.  Whereas DHEA levels naturally reach their peak in
the early morning hours, DHEAS levels show
no diurnal variation.
 From a practical point of view, measurement of
DHEAS is preferable to DHEA, as levels are more
stable.

8. History of use in poor responders
 Casson et al.2000
 Self-controlled trial, five women, previous poor
responders.
 Increased peak E2 levels (939.8 versus 266.3
pg/ml, P = 0.02) and yielded more oocytes (2.2
versus 1) following DHEA treatment .
 Criticized due to methodological errors - bias caused
by the change in the stimulation protocol, as well as
the type and dose of gonadotrophins administered.

9. POSSIBLE MECHANISM OF ACTION
 Direct effect of DHEA on the aging ovary
 A) by increasing the pool of follicles up to the pre-
antral stage or
 B) reducing apoptosis of the originally recruited
follicles (Gleicher et al 2010)
 DHEA does not appear to exert influence via
recruitment of pre-antral or very small antral
follicles (no change in AMH and inhibin B) but
rather by rescue from atresia of small antral follicles
(increased AFC). Hyman et al 2013

10. Review of literature
 Barad and Gleicher
 42.7 Year old woman, self medication. 9 IVF in 11 months
-66 embryos!(2005)
 Self-controlled study ,25 patients ,DOR defined as a
history a prior IVF cycle with less than four oocytes and
uniformly poor quality embryos.
 . Following DHEA, an increased oocyte yield, a higher
fertilization rate and a higher embryo grade were
achieved.(2006)

11.  Case–control study , 89 patients with DOR who had
used DHEA with 101 matched controls (2007)
 DOR was defined as the presence of an elevated agespecific FSH concentration.
 The treatment group showed an increased
pregnancy rate (28.4 versus 11.9%,P < 0.05)
following DHEA use for a mean duration of 73 days .

12.  Same authors also compared miscarriage rates in
patients who had used DHEA with those rates
reported in the National US IVF database and
suggested that the DHEA-supplemented group had
significantly lower miscarriage rates (2009).

13.  Gleicher et al 2010
 Self controlled trial
 Increase in AMH after DHEA use in proportion to
duration of use, more in younger women.
 Increase in pregnancy when AMH rise occurred.

14.  Gleicher 2010
 Case controlled study(22 women who had been using
DHEA with 44 age-matched women serving as
controls)
 Lower aneuploidy rates after DHEA intake((38.2
versus 61%).
 Those on DHEA produced a mean of 9.6 eggs versus
11.7 in the control group.

15.  A case series
 Greece
 Five patients with post-menopausal FSH levels who
conceived following 45–189 days of DHEA
supplementation (Mamas and Mamas 2009)

16.  Prospective self-controlled pilot study of 8 women
failed to observe any difference in the number of
oocytes and embryo quality following 3 months of
DHEA supplementation (Motta et al 2006).
 Borman et al. found no difference in the mean
DHEA levels in poor and relatively good responder
patients (2010).

17. RCT
 33 women younger than 42 years of age who either
yielded fewer than five oocytes, had poor quality
embryos or had cycle cancellation due to poor
ovarian response were randomized to receive 75 mg
DHEA or nothing for an average duration of 13.5
weeks prior to undergoing repeat treatment using
the same ovarian stimulation protocol (Wiser et al.,
2010).

18.  No significant difference between the DHEA and
control groups in terms of primary outcome
measures (peak E2 levels, mean number of retrieved
oocytes and embryo quality).
 Among 17 patients in the DHEA group, there were seven
pregnancies (26.9%) and six live births (23.1%) following
26 treatment cycles.
 However, among 16 patients in the control group, there
were only three pregnancies (12%) and a single live birth
(4%). The difference between live birth rates was
reported as statistically significant (P = 0.05).

19.  The use of androgens or androgen-
modulating agents in poor responders
undergoing in vitro fertilization: a systematic
review and meta-analysis. (HR UPDATE
2012)
 There is insufficient data to support a beneficial role
of, DHEA administration in the probability of
pregnancy in poor responders undergoing ovarian
stimulation for IVF.

20. OUR EXPERIENCE IN IRM&WH
 Retrospective analysis of IVF records (May 2012-
May 2013)
 All patients who fulfilled Bologna criteria were
identified.
 All women who fulfilled the criteria and had taken
DHEA for at least 12 weeks prior to their IVF/ICSI
were included in the study groups.
 Others were taken in the control group.

21. 






DHEA (n=32)
Age
34.3 +/- 6.5
Duration
6.7+/- 4.1
Duration of Gn
10+/-1.3
Total dose of Gn
4143+/-816
No: of eggs
2.9+/-1.5
No: of embryos tr
1.65+/-1.2
Non DHEA (87) P
34.6 +/- 4.3 0.68
8.3+/-4.6
0.873
10.1+/-1.6
0.85
4030+/-980 0.80
3+/-1.3
0.58
2+/-1.4
0.23

22. 
 No: of cancelled cycles
 No of clinical pregnancy
 No of ongoing pregnancy
 No: of miscarriage
 No: of ectopic/PUL
 No: delivered
DHEA Non DHEA
6/32
11/87
5
7
4
2
1
4
2
3
2
1

23. Conclusion
 We need more multicentre RCTs before DHEA can
be recommended for routine use in expected poor
responders.
 Lack of harm is not sufficient to promote the use of a
drug in any given clinical situation and the practice
of poly pharmacy should be reduced.

24.  THANK YOU!