Download DHEA and Androgen Supplementation

DHEA and Androgen Supplementationfor
Assisted Conception/Fertility
What Are Androgens?
Why is DHEA recommended ?
Both men and women produce the hormone testosterone.
Testosterone and several similar related hormones are known
as androgens and are vital to the normal function of the female
reproductive system especially the normal development of
follicles and eggs in the ovary..
Recently DHEA has been recommended as an adjunct to
fertility treatment for patients with diminished ovarian
reserve, this can be a natural process through ageing especially
for women in their 40s or can be due to premature ovarian
ageing in younger women (this can occur in up to 10% of the
population).
Why are Androgens recommended?
The use of Androgen treatment in women is based on
observations in women and on experimental animal studies..
Women with lower levels of testosterone are less likely to
achieve pregnancy than women with higher levels and also
respond less well to standard ovulation inductions, it is also
known that androgen levels decrease with age, and this
is especially true in women who’s Studies in non-human
primates suggest that pre-treatment with androgen increases
the ability of the cells around the egg to respond to to the
hormone that grows the follicles containing eggs(FSH).
Androgen pre-treatment in monkeys promotes development
of extra eggs within the ovaries and increases the number
of small follicles within the ovaries.. All of these findings are
consistent with the hypothesis that androgen pre-treatment
in women increases the number of eggs available for retrieval
with IVF in women with decreased ovarian reserve. In one
study it was found that low levels of the hormone testosterone
on day 3 of ovarian stimulation was associated with a poorer
outcome to treatment (1)
What androgens are used in fertility treatment
There are two main androgens that have been used and
studied in assisted conception treatment , these are
Dehydroepiandrostenendione or DHEA and testosterone.
Dehydroepiandrostenendione(DHEA)
Supplementation
What is DHEA?
DHEA is an abbreviation for Dehydroepiandrosterone, This
is a naturally occurring hormone produced primarily in the
adrenal glands (glands on top of the kidney). DHEA is also
produced in other parts of the body including the testicles,
ovaries, and brain. After production, the bloodstream carries
DHEA to tissues and cells. Some of it is converted to sex
hormones testosterone and estrogens.
Nuffield Health, The Grosvenor Hospital
Wrexham Road, Chester, CH4 7QP
t: 01244 684325
f: 01244 680812
Chester Wellness Centre
Wrexham Road, Chester, CH4 9DE
t: 01244 677797
f: 01244 674222
e: [email protected]
www.cheshirewomenshealth.co.uk
Studies have shown that in patients with diminished ovarian
reserve there is a significant increase in eggs retrieved from
stimulation of the ovaries, with better quality embryos, higher
pregnancy rates and lower miscarriage rates.
Who should consider DHEA?
Studies have shown that DHEA is beneficial in patients with
diminished ovarian reserve, this includes ladies who:
•
Are over 40 years of age
•
Have an AMH (anti Mullerian Hormone) level
significantly lower than expected for Age , or <8pmol/l
•
Have a significantly elevated FSH ( Follicle Stimulating
Hormone) level for age, level >12
•
Have had previous poor response to ovarian stimulation
(low egg yield, poor fertilisation, poor embryo
development and quality)
For levels of AMH and FSH indicating possible diminished
ovarian reserve for age See appendix A
There is no evidence of benefit of DHEA supplementation
in ladies who do not have diminished ovarian reserve or
premature ovarian ageing.
What is the evidence for benefit?
Since 2010 there have been growing number of studies
worldwide, including a number of controlled studies (2,3) that
have confirmed the benefit of supplementation with DHEA
prior to Assisted Conception treatment, with some other
studies showing an improvement in natural conception as well
as pregnancies with very low AMH levels(4)
There is significant evidence from studies including a couple of
hundred patients supplemented with DHEA during IVF that
have had:
Complete Healthcare for Women
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DHEA and Androgen Supplementationfor
Assisted Conception/Fertility
conditions or liver disease. If you have any medical problem or
are taking any medications (like drugs for depression, blood
pressure medications, steroids, diabetes medications, insulin)
please let us know.
•
increased number of eggs retrieved and therefore
•
increased number of available embryos to transfer and
•
improved quality of embryos transferred.
•
There is some evidence that DHEA supplementation
could
•
increase the number of chromosomally normal embryos,
Some non fertility trials have shown some potential additional
benefits to DHEA supplementation in women including,
improvement in memory, energy, libido, concentration and
general wellbeing.
•
improve the clinical pregnancy rate
For a full list of side effects and possible drug interactions
•
improve live birth rate
www.nlm.nih.gov/medlineplus/druginfo/natural/331.html
•
increase spontaneous conceived pregnancies and reduce
miscarriage rate
What Dose Should I Take and When?
There is evidence that supplementation with DHEA could
significantly increase your AMH value which correlates with
the ovarian reserve and the response to treatment.
What are the side effects?
As DHEA is an abundant naturally occurring hormone, the
side effects are mild with the most common side effects noted
being related to an increase level of serum testosterone (male
hormone) concentrations. Therefore there is a small risk of
having male hormone side effects like acne (on the face, chest
or the back), oily skin, increased facial hair growth, increased
perspiration and weight gain. There is an even lower chance of
having mild hair loss and deepening of the voice. These side
effects generally disappear when DHEA is discontinued. Other
possible side effects are menstrual irregularities, irritability
and restlessness.
There have been some reports where people who take
large doses of DHEA (higher than proposed for your own
treatment) can have irregular heartbeats or palpitations. If you
have any of those symptoms please contact us and stop the
medication immediately. At higher doses than used for fertility
supplementation, significant side effects have been observed
(e.g. blood clots).
Women with a personal history hormone related disorders
(like history of breast or uterus cancer, endometriosis,
fibroids) should not take DHEA. It could cause significant
complications to patients with a history of head injury,
diabetes, high cholesterol, thyroid disorders, other hormonal
Nuffield Health, The Grosvenor Hospital
Wrexham Road, Chester, CH4 7QP
t: 01244 684325
f: 01244 680812
Chester Wellness Centre
Wrexham Road, Chester, CH4 9DE
t: 01244 677797
f: 01244 674222
e: [email protected]
www.cheshirewomenshealth.co.uk
The dose used in most studies and therefore recommended
has been 75mg of DHEA per day taken for at least 3 months
prior to fertility treatment. The commonest tablet available is
25mg and should be taken three times daily.
The beneficiary effects from DHEA become apparent after 2-4
months of supplementation. You should continue the tablet
until the night of the triggering injection for IVF (e.g.Pregnyl/
Ovitrelle).
Why is it not prescribed and how much does it cost ?
In the USA it is considered a food supplement and available
over the counter but in the UK this is not the case and, as
it is not a licensed drug, it cannot be prescribed through
pharmacies in the normal way. This drug can be purchased
through reputable health-food retailers. DHEA is classified as
a naturally occurring hormone precursor and is treated as a
health supplement; it is therefore available over the counter or
via the internet.
At Cheshire Womens Health we have organised the purchase
and provision of reliable stocks of DHEA that is available
in clinic. If you would like to purchase this please contact
CWH on 012444 677797 to arrange to collect this at your
convenience
How do I obtain treatment?
The easiest way to reliably obtain DHEA is via Cheshire
Womens Health and patients can purchase this at any time
by contacting the clinic, alternatively it can be purchased with
care over the internet
Complete Healthcare for Women
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DHEA and Androgen Supplementation for
Assisted Conception/Fertility
Testosterone Supplementation
How is and when is the testosterone given?
Why is the “male “hormone testosterone used?
Testosterone supplementation used to be given with a
specially designed patch that was at a dose that was suitable
for prescribing to women. Unfortunately this patch is no
longer available and instead supplementation is given using gel
designed for male use. This requires very careful prescribing
and use and you will be advised carefully by your clinician.
For patients with significantly decreased ovarian reserve
there is evidence that the levels of naturally occurring
androgens/ testosterone are much lower and that additional
supplementation with testosterone is required to produce
a more normal hormonal balance at the time of ovarian
stimulation
What evidence is there for benefit?
Unfortunately all the evidence for benefit of testosterone
supplementation comes from very small studies or from
pooling the data from many smaller studies ( a meta analysis).
In one small study of only 25 patients with previous multiple
poor responses to ovarian stimulation there was a 5 fold
increase in retrieved oocytes(5) In the largest study of 225
patients who had previously responded poorly there was an
increase number of eggs and embryos created in the patients
supplemented with testosterone and a higher pregnancy rate,
however the pregnancy rate per embryo transferred was not
different suggesting that whilst it may improve the recovery of
eggs it does not improve the quality of embryos(6)..
When should this be given?
It is recommended that the testosterone supplementation
is taken for a minimum of 5 days prior to starting ovarian
stimulation.
How can I obtain Testosterone supplementation ?
Testosterone supplementation is only available on prescription,
If your clinician feels that supplementation with testosterone
before your fertility treatment is advised you will be issued
with a prescription at the same time as your other fertility
drugs.
For more information with regard to DHEA and androgen
supplementation or to order DHEA please contact CWH on
01244 677797.
Who should use testosterone supplementation?
References
The evidence for benefit for Testosterone is only present in
patients with very diminished ovarian reserve, AMH < 1 or
when patients who have had a previous cycle of treatment
with DHEA supplementation have had a poorer than expected
response.
1. Association of basal serum testosterone levels with ovarian
response and in vitro fertilization outcome. Quin Y et Al.
Reprod Biol Endocrinol 2011 Jan 20;9:9.
What Side effects will I experience?
The treatment that we use is patch that has been regularly
used for long term supplementation for women who have
experienced the menopause after the surgical removal of their
ovaries, As such the dose is lower than normal patches and is
designed for long term use without any significant side effects.
As this supplementation is only used for the 2-3 weeks leading
up to your treatment we would not expect any side effects
other than occasionally irritation to the skin at the application
site in sensitive individuals.
Nuffield Health, The Grosvenor Hospital
Wrexham Road, Chester, CH4 7QP
t: 01244 684325
f: 01244 680812
Chester Wellness Centre
Wrexham Road, Chester, CH4 9DE
t: 01244 677797
f: 01244 674222
e: [email protected]
www.cheshirewomenshealth.co.uk
2. Update on the use of dehydroepiandrosterone
supplementation among women with diminished
ovarian reserve. Barad DH, et al, J Assist Reprod Genet
2007;24(12):629-34.
3., Miscarriage rates after dehydroepiandrosterone (DHEA)
supplementation in women with diminished ovarian reserve:
a case control study. Gleicher N, et al Reprod Biol Endocrinol
2009;7(7):108.
4. Live birth chances in women with extremely low-serum
anti-Mullerian hormone levels. Weghofer A, et al, Hum
Reprod 2011;26(7):1905-9.
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DHEA and Androgen Supplementation for
Assisted Conception/Fertility
5. Pretreatment with transdermal testosterone may improve
ovarian response to gonadotrophins in poor-responder IVF
patients with normal basal concentrations of FSH . Balasch et
al. Hum Reprod 2006;21(7):1884-1893
6. Effects of transdermal testosterone in poor responders
undergoing IVF: systematic review and meta-analysis..
Gonzalez-ComadrenM et al Reprod Biomed online. 2012 Jul
26 pii S1472-6483
Levels of AMH indicating age specific decreased
ovarian reserve
Age
AMH less than pmol/L
20-24
11.9
25-29
8.4
30-34
6.8
35-39
5.5
40-44
0.7
Nuffield Health, The Grosvenor Hospital
Wrexham Road, Chester, CH4 7QP
t: 01244 684325
f: 01244 680812
Chester Wellness Centre
Wrexham Road, Chester, CH4 9DE
t: 01244 677797
f: 01244 674222
e: [email protected]
www.cheshirewomenshealth.co.uk
Complete Healthcare for Women
Page 4