Q&A 435.1
Is there any evidence that DHEA supplementation improves female fertility?
Prepared by UK Medicines Information (UKMi) pharmacists for NHS healthcare professionals
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Date prepared: 31st March 2014
Background
Dehydroepiandrosterone (DHEA) is a natural steroid hormone abundantly secreted by the adrenal glands. It acts as a precursor to several other hormones and has also been shown to stimulate insulin growth factor-1 [IGF-1].(1) It is produced synthetically or can be derived in the lab from soy or wild yam, although DHEA cannot be produced in the human body following ingestion of these plants or their extracts.(2)
Health claims for DHEA supplementation are wide ranging, and include reversing aging, slowing Alzheimer’s and Parkinson’s disease progression, erectile dysfunction, prevention of various cancers and others. However, evidence to support these purported uses is generally lacking.(1, 2)
Most forms of assisted reproductive technology rely on ovarian stimulation by administering large doses of exogenous gonadotrophins. However, patients with a diminished ovarian reserve (DOR) do not have an adequate response to this practice, rendering them difficult to treat. The most common reason for DOR is advanced age (over 41 years), though it may also occur in younger women.(3)
Answer
Mechanism
The action of DHEA on IGF-1 forms the basis of its use in female infertility. Administration of growth hormone is thought to improve oocyte yields through production go IGF-1- therefore it is hypothesized that DHEA may do the same.(4)
Evidence
Evidence of DHEA’s efficacy is limited by methodological problems. Because women with DOR have a limited time for conception, many are unwilling to enter a randomised placebo controlled trial. This has led to the abandonment of several clinical trials.(4)
As a result, only one randomised controlled trial has been published in the medical literature to date. This trial recruited patients who had previously shown a poor response to ovarian stimulation in a previous IVF cycle who had not previously received DHEA supplementation. 33 women were enrolled in the study, of which 17 were assigned to the DHEA group and 16 to the control group. Results of this trial were promising, with a significantly higher live birth rate in the DHEA group compared to the control group (6 live births vs 1 live birth, p=0.05). A greater success rate was seen in patients with secondary infertility than primary. There are several limiting factors in the applicability of this study, including the use of an open-labelled design and the small number of subjects. The lack of prior information and trials also meant that the authors were unable to reliably determine the adequate number of patients required to power the study. The exclusion of women aged over 42 years old may not reflect the demographic group that is most likely to suffer from DOR.(5)
A case series of 5 women with DOR and normal FSH levels found that DHEA supplementation increased gonadotrophin response by around two fold. One pregnancy occurred. Again, older women were not included in this series, limiting its usefulness in this age range.(3)
Safety
DHEA appears to be well tolerated in the short term at doses such as 50mg per day. For the treatment of DOR, doses in the range of 75-80mg daily are given. Adverse effects become more frequent at higher doses of 200mg and over, and include acne, hirsutism, hair loss, voice deepening, insulin resistance, and menstrual cycle changes.
There is little known about the long term safety of DHEA. Studies looking at its various uses have been limited to a maximum of 6 months. There is a theoretical concern that long term usage of high doses of DHEA could increase the risk of some hormone-sensitive cancers.
There is a lack of safety information of DHEA in pregnancy, which is of particular relevance to its use in fertility treatment. As it can cause increased androgen levels, its use during pregnancy and lactation should be avoided until more is known.(2)
Any adverse reactions suspected to be caused by DHEA should be reported to the MHRA’s Yellow Card Scheme. Further information on reporting side effects of medicines may be found at www.mhra.gov.uk/yellowcard
Summary
DHEA increases levels of androgens and IGF-1. It may therefore improve fertility in women with DOR, though robust clinical evidence for these actions is lacking.
The limited trial information available excludes women older than 42 years of age. The usefulness of DHEA in this age group therefore remains unknown.
Limitations
The limitations of the available evidence are discussed above.
Quality Assurance
Prepared by
Hayley Johnson, Regional Drug & Therapeutics Centre, Newcastle
Date Prepared
31st March 2014
Checked by
Nancy Kane, Regional Drug & Therapeutics Centre, Newcastle
Date of check
10th April 2014
Search strategy
Embase (incorporating Medline): *Prasterone/ AND female infertility/
Natural Medicines Comprehensive Database
Medicines Complete
MHRA
References
1. Dehydroepiandrosterone. In: Dietary Supplements [online]. London: Pharmaceutical Press. [cited 2014 31st March]; Available from: http://www.medicinescomplete.com
2. DHEA. In: Natural Medicines Comprehensive Database. Last updated 29/04/2013. [cited 2014 31st March]; Available from: http://naturaldatabase.therapeuticresearch.com
3. Casson PR LM, Pisarka MD, Carson SA, Buster JE,. Dehydroepiandrosterone supplementation augments ovarian stimulations in poor responders: a case series. Human Reproduction. 2000;15(10):2129-32.
4. Gleicher N, Barad DH. Dehydroepiandrosterone (DHEA) supplementation in diminished ovarian reserve (DOR). Reprod Biol Endocrinol.9:67.
5. Wiser A, Gonen O, Ghetler Y, Shavit T, Berkovitz A, Shulman A. Addition of dehydroepiandrosterone (DHEA) for poor-responder patients before and during IVF treatment improves the pregnancy rate: a randomized prospective study. Hum Reprod. Oct;25(10):2496-500.
3
Available through NICE Evidence Search at www.evidence.nhs.uk