DHEA- WONDER DRUG?
DR.SATHYA BALASUBRAMANYAM
MD,DNB,MRCOG,FNB(REPROD MED)

INSTITUTE OF REPRODUCTIVE MEDICINE
AND WOMEN’S ...
 What is DHEA?
 History of use in poor responders
 Review of literature
 Our experience in IRM&WH
 Conclusions
What is DHEA?
 DHEA is an important endogenous steroid

hormone.
 It is the most abundant circulating steroid in

humans...
Place in the steroid synthetic pathway.
 Cholesterol--- Pregnenolone---17 alpha

Pregnenolone----DHEA---- Androgens---- E...
Are DHEA and DHEAS different?
 DHEAS is the sulfate ester of DHEA. This conversion

is reversibly catalyzed by sulpho tra...
 In the blood, most DHEA is found as DHEAS with

levels that are about 300 times higher than those of
free DHEA.
 Orally...
 Whereas DHEA levels naturally reach their peak in

the early morning hours, DHEAS levels show
no diurnal variation.
 Fr...
History of use in poor responders
 Casson et al.2000
 Self-controlled trial, five women, previous poor

responders.
 In...
POSSIBLE MECHANISM OF ACTION
 Direct effect of DHEA on the aging ovary
 A) by increasing the pool of follicles up to the...
Review of literature
 Barad and Gleicher
 42.7 Year old woman, self medication. 9 IVF in 11 months

-66 embryos!(2005)

...
 Case–control study , 89 patients with DOR who had

used DHEA with 101 matched controls (2007)
 DOR was defined as the p...
 Same authors also compared miscarriage rates in

patients who had used DHEA with those rates
reported in the National US...
 Gleicher et al 2010
 Self controlled trial
 Increase in AMH after DHEA use in proportion to

duration of use, more in ...
 Gleicher 2010
 Case controlled study(22 women who had been using

DHEA with 44 age-matched women serving as
controls)
...
 A case series
 Greece
 Five patients with post-menopausal FSH levels who

conceived following 45–189 days of DHEA
supp...
 Prospective self-controlled pilot study of 8 women

failed to observe any difference in the number of
oocytes and embryo...
RCT
 33 women younger than 42 years of age who either

yielded fewer than five oocytes, had poor quality
embryos or had c...
 No significant difference between the DHEA and

control groups in terms of primary outcome
measures (peak E2 levels, mea...
 The use of androgens or androgen-

modulating agents in poor responders
undergoing in vitro fertilization: a systematic
...
OUR EXPERIENCE IN IRM&WH
 Retrospective analysis of IVF records (May 2012-

May 2013)
 All patients who fulfilled Bologn...









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: o...

 No: of cancelled cycles
 No of clinical pregnancy
 No of ongoing pregnancy
 No: of miscarriage
 No: of ectopic/PUL...
Conclusion
 We need more multicentre RCTs before DHEA can

be recommended for routine use in expected poor
responders.
 ...
 THANK YOU!
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Dhea wonder drug

  1. 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. 2.  What is DHEA?  History of use in poor responders  Review of literature  Our experience in IRM&WH  Conclusions
  3. 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. 4. Place in the steroid synthetic pathway.  Cholesterol--- Pregnenolone---17 alpha Pregnenolone----DHEA---- Androgens---- Estrogens
  5. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 24.  THANK YOU!
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