DRUG REVIEW PROSPECTIVE SELF-CONTROL STUDY

https://doi.org/10.5005/jp-journals-10006-1748
Journal of South Asian Federation of Obstetrics and Gynaecology
Volume 12 | Issue 1 | Year 2020

Dehydroepiandrosterone: Is it a Magic Drug?

Neharika Malhotra¹, Jaideep Malhotra², Keshav Malhotra³, Shally Gupta⁴

^1–4Rainbow IVF, Rainbow Hospitals, Agra, Uttar Pradesh, India

Corresponding Author: Jaideep Malhotra, Rainbow IVF, Rainbow Hospitals, Agra, Uttar Pradesh, India, Phone: +91 9897033335 e-mail: jaideepmalhotraagra@gmail.com

How to cite this article Malhotra N, Malhotra J, Malhotra K, et al. Dehydroepiandrosterone: Is it a Magic Drug? J South Asian Feder Obst Gynae 2020;12(1):59–61.

Source of support: Nil

Conflict of interest: None

ABSTRACT

With infertility populations in the developed world rapidly aging, treatment of diminished ovarian reserve (DOR) assumes increasing clinical importance. In developing countries like India, many patients due to economic and cultural restraints are not able to afford ovum donation or other assisted reproductive techniques. Thus, the possibility of a significant improvement in ovarian response with such an intervention in cases of DOR seems to be very promising. Our findings show only an improvement in anti-mullerian hormone (AMH) levels and antral follicle count in women with poor ovarian reserve, which was statistically significant. But we need a bigger sampling size.

Keywords: Anti-mullerian hormone, Dehydroepiandrosterone, Infertility, Poor ovarian reserve..

INTRODUCTION

As we know infertility populations is rising all over the world, managing diminished ovarian reserve (DOR) is very important.

Many studies have been reported to have improve outcome with dehydroepiandrosterone (DHEA) pretreatment.

Diminished ovarian reserve is where the ovaries lose it capability to act in a desired manner affecting reproductive outcome.

Anti-mullerian Hormone

There is no specific time for the test.
Low values of anti-mullerian hormone (AMH) are associated with poor ovarian response but it does not predict failure to conceive.

AFC (Antral Follicle Count) Ideally to be Seen on Day 2/Day 3

Number of visible follicles (2–10 mm) during transvaginal ultrasound.
Performed on cycle days 2–5.
Number of antral follicles correlates with ovarian response to stimulation.
Does not predict failure to conceive.

Action

Dehydroepiandrosterone is an endogenous steroid hormone.

It is produced in the adrenal glands (zona reticularis) and the gonads, and functions predominantly as a metabolic intermediate in the biosynthesis of the androgen and estrogen sex steroids.

Dehydroepiandrosterone does show many effects on reproduction and has a binding effect on an array of receptors (Fig. 1).

MECHANISM OF ACTION

We still are unsure of the direct mechanism of DHEA on ovary.

Acts as prehormone of the follicular fluid testosterone during the administration of gonadotropins for ovulation induction, which leads to the formation of estradiol.¹
Barad et al. (2006)—androgens can be a metabolic precursor for steroid production and it acts as ligands for androgen receptors, thus influencing follicular growth in ovaries.²
From the theory by Barad et al., we know that DHEA acts like PCO creation to an aging ovary.²
Casson et al. also hypothesized that the beneficial effect of DHEA may be due to an increase in insulin-like growth factor-I.³
From many studies, we know DHEA has a cumulative effect.⁴ This increase in preantral and antral follicles leads to an increase in AMH production and more follicles become available for induction with gonadotropins which is reflected by a fall in serum FSH and rise in serum estradiol.
As an immune regulator, it enhances the Th1 immune response and regulates the balance of the Th1/Th2 response. Upregulation of the CD8+ T lymphocyte population in ovarian tissue, thus regulating the balance of CD4+/CD8+ T cells.⁵

AIM

To assess the effect of DHEA supplementation on diminished ovarian reserve in infertile patients

OBJECTIVE

To evaluate the effect of DHEA supplementation on ovarian reserve by measuring markers, such as, antral follicle count and serum AMH in patients with diminished ovarian reserve.

MATERIALS AND METHODS

A prospective self-controlled study was conducted at Rainbow IVF Hospital, Agra from January 2019 to January 2020.
Total 30 patients of infertility were recruited based on inclusion and exclusion criteria.
Informed consent was taken for all patients.
The study population was divided into two age groups (<35 and ≥35 years) to determine whether there was a difference in the effect of DHEA supplementation between younger and older patients with diminished ovarian reserve.
Baseline serum AMH and antral follicle count (D2 Ultrasound) were noted.
All patients received DHEA supplementation in the form of 75 mg sustained release tablet to be taken once daily for 3 months.
A repeat serum AMH and antral follicle count were done after 3 months.
Difference in the AMH and AFC before and after DHEA supplementation was noted. To evaluate whether change in AMH and AFC was significant, Mc Nemar test was applied using SPSS 20.

Fig. 1: Synthesis of dehydroepiandrosterone

OUTCOME

Primary Outcome

Improvement in serum AMH level.
Improvement in antral follicle count.

Secondary Outcome

Determined whether there was a difference in the effect of DHEA supplementation between younger and older patients with diminished ovarian reserve.

INCLUSION CRITERIA

Women seeking treatment for infertility with an abnormal ovarian reserve test
Antral follicle count ≤5 and/or anti-mullerian hormone ≤1 ng/mL.

EXCLUSION CRITERIA

H/o ovarian cystectomy/oopherectomy
Diagnosis of endometriosis
Abnormal thyroid/liver/kidney function
On anticonvulsant therapy

DISCUSSION

With infertility populations in the developed world rapidly aging, treatment of DOR assumes increasing clinical importance.
In developing countries like India, many patients due to economic and cultural restraints are not able to afford ovum donation or other assisted reproductive techniques. Thus, the possibility of a significant improvement in ovarian response with such an intervention in cases of DOR seems to be very promising.
Our findings show only an improvement in AMH levels and antral follicle count in women with poor ovarian reserve which was statistically significant.
On close observation, the mean increase in AMH and AFC is more in the younger population (<35 years) indicating more beneficial role in younger population with diminished reserve and further emphasizing the role of age as a marker for ovarian reserve (Tables 1 and 2).
The data support the meta-analysis of 2011, which says that role of DHEA in improving ovarian reserve is effective (Figs 2 and 3).

LIMITATION

The sample size is small so we need to further study to draw significant conclusions.

**Table 1**: Study statistics
Age group	Baseline AMH (mean ± SD) (ng/mL)	AMH after 3 months (mean ± SD) (ng/mL)	Mean difference (95% confidence interval)	p value
<35 years (n = 14)	1 ± 0.32	1.4 ± 0.28	0.4 (0.16–0.66)	0.001
≥35 years (n = 16)	0.78 ± 0.23	0.97 ± 0.24	0.19 (0.02–0.35)	0.003

**Table 2**: Our study statistics
Age group	Baseline AFC (mean ± SD)	AFC after 3 months (mean ± SD)	Mean difference (95% confidence interval)	p value
<35 years (n = 14)	2.14 ± 0.66	3.57 ± 0.94	1.4 (0.79–2.06)	0.001
≥35 years (n = 16)	1.63 ± 0.81	2.00 ± 0.73	0.38 (0.05–0.70)	0.02

Fig. 2: Comparison of AMH levels before and after DHEA supplementation for 3 months

CONCLUSION

Our findings show an improvement in AMH levels and antral follicle count in women with poor ovarian reserve which was statistically significant.
The improvement in mean levels of AMH and AFC was more in younger age group (<35 years).
But due to small sample size, there is a need to continue this study and draw conclusions on a larger sample size.

Fig. 3: Comparison of AFC levels before and after DHEA supplementation for 3 months

REFERENCES

1. Haning RVJr, Hackett RJ, Flood CA, et al. Plasma dehydroepiandrosterone sulfate serves as a prehormone for 48% of follicular fluid testosterone during treatment with menotropins. J Clin Endocrinol Metab 1993;76(5):1301–1307. DOI: 10.1210/jcem.76.5.8496321.

2. Barad D, Gleicher N. Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF. Hum Reprod 2006;21(11):2845–2849. DOI: 10.1093/humrep/del254.

3. Casson PR, Lindsay MS, Pisarska MD, et al. Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod 2000;15(10):2129–2132. DOI: 10.1093/humrep/15.10.2129.

4. Barad DH, Gleicher N. Increased oocyte production after treatment with dehydroepiandrosterone. Fertil Steril 2005;84(3):756. DOI: 10.1016/j.fertnstert.2005.02.049.

5. Zhang J, Qiu X, Gui Y, et al. Dehydroepiandrosterone improves the ovarian reserve of women with diminished ovarian reserve and is a potential regulator of the immune response in the ovaries. Biosci Trends 2015;9(6):350–359. DOI: 10.5582/bst.2015.01154.

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