Transcript Dehydroepiandrosterone sulfate

DEHYDROEPIANDROSTERONE
(DHEA)
DR.T.RAMANIDEVI MD DGO FICS FICOG
DIRECTOR, JANANI FERTILITY CENTRE
RAMAKRISHNA NURSING HOME
TRICHY
Introduction
5-Dehydroepiandrosterone (5-DHEA)
• 19-carbon endogenous natural steroid hormone
• It is the major secretory steroidal product of the
adrenal glands and is also produced by the gonads
and the brain
• DHEA converted to
-50% of circulating testosterone in men
-75% estrogen in women in perimenopausal age group
- 100% in postmenopausal women
DHEA
DEHYDRO EPIANDROSTERONE (DHEA)
• Derived from cholesterol
• Androgen precusor
• Maximum concentration at 20’s
• Decreases to 10-20 % by 80’s
DEHYDRO EPIANDROSTERONE (DHEA)
CHOLESTEROL
PREGNENOLONE
DHEA
DHEAS
ANDROSTENEDIONE
TESTOSTERONE
OESTROGEN
DEHYDRO EPIANDROSTERONE (DHEA)
• Supplements are made from substances called
“Disogenin”
• “Disogenin” is rich in soy and wild yams.
• Only micronised forms of dhea are absorbed.
DEHYDRO EPIANDROSTERONE (DHEA)
• Metabolised in liver
• 50-70 % excreted by renal system
• Half life : 7 - 38 min.
Mechanism of action
Effect of Oral DHEA may be due to weak
androgenic or estrogenic activity and to the
fact that it is metabolized to androgens and
estrogens
NORMAL LEVEL OF DHEA – 80µg/dl
to 320µg/dl
DEHYDRO EPIANDROSTERONE (DHEA)
Low levels of DHEA is associated with
Ageing/ Alzhiemers
Obesity
Type II DM
Immune dysfunction
Autoimmune disease
Cancer
DEHYDRO EPIANDROSTERONE (DHEA)
Low levels of DHEA is associated with
 Depression
 Loss of well being
 CVS problems
 Osteoporosis
 Erectile dysfunction
 Low libido
• Infertility
Role of DHEA in
infertility
Role of DHEA
other than
infertility
Clinical
application of
DHEA
Interactions,
contraindications
and side effects
of DHEA
DHEA
1.DHEA TO IMPROVE OVARIAN FUNCTION
Increase antral
follicles
Increase no of
mieotically active
oocytes
Decrease
follicular
atresia
Increase
ovarian
steroidogenesis
DHEA
Reprod Biomed
Online. 2009
Oct;19(4):508-13.
2.Pre conditions the ovary for
ovulation induction
DHEA supplementation for
production of estrogen in the
ovaries
Improves follicular dynamicsenhances aromatase activity
required for improved E2 levels
Better ovarian function in women
with increased resistance to OI –
increase no of oocytes and embryos
favoring clinical pregnancies
FERTILITY AND STERILITY SEP 2005
ACTION OF DHEAS
PROHORMONE
IMPROVES
REDUCES
OVARIAN
APOPTOSIS
RESERVE
DHEA IMPROVES
AUGMENTS
IGF -1
OVARIAN
ENVIRONMENT
Who require DHEA?
• Women with
▫ Physiological ovarian ageing
( all above age 40 )
▫ Premature ovarian ageing
( Below the age of 38)
DEHYDRO EPIANDROSTERONE (DHEA)
Physiological Ovarian Ageing
• All women above age of 40 with decreased
fertility
• Poor ovarian reserve due to age
DEHYDRO EPIANDROSTERONE (DHEA)
Premature ovarian ageing
• Function of the ovary is impaired
• FSH level above 95 % tile
• AMH below 95 %tile for her age
DEHYDRO EPIANDROSTERONE (DHEA)
PREMATURE OVARIAN AGEING
TESTOSTERONE EVALUATED
• UPPER 1/3 OF NORMAL
• LOW 2/3 OF NORMAL
• NO DHEA
• DHEA GIVEN
3.ROLE IN POF/POI
Increase in oocyte production after treatment with DHEA
DEHYDRO EPIANDROSTERONE (DHEA)
• AMH – GOLD STANDARD ASSESSMENT
OVARIAN RESERVE
DEHYDRO EPIANDROSTERONE (DHEA)
• AMH increases in parallel with length of DHEA
supplementation
• This increase is more pronounced in younger
POF than older DOR patients
• Improvement in AMH levels predicts pregnancy
success.
Gleicher et al, rep.biomed online 2010.,
4.Reduces IVF cancellation rates
• DHEA supplementation shows increase in IGF1
concentrations to potentiate gonadotrophin
action in women with diminished ovarian
reserves
Hum Reprod. 2010 Oct;25(10):2496-500. Epub 2010 Aug 21.
• Increase in average embryo scores per oocyte in
IVF cycle outcomes and reduces IVF cancellation
rates
Hum Reprod. 2000 Oct;15(10):2129-32.
• DHEA supplementation facilitates
gonadotrophins effect, it also reduces the dose of
gonadotrophins in IVF cycles
Human reproductions sep 2006
Effect of dehydroepiandrosterone on oocyte and embryo
yields, embryo grade and cell number in IVF
(Ref. 1 Human Reproduction 2006; 21: 2845-2849
5.Reduces miscarriage rates
• DHEA supplementation has shown to have
progestogenic effects in women with age related
poor ovarian function to support conception and
prevent miscarriages
• DHEA
augument gonadotrophin secretion
augment HCG secretion to support corpus
luteum for production of progesterone to
support pregnancy
• Overall reduces miscarriages and improve
cumulative pregnancy outcome
Fertility and sterility sep 2006
Miscarriage rates after dehydroepiandrosterone (DHEA)
supplementation
Ref. 1 Reproductive Biology and Endocrinology 2009, 7:108 )
Effect on pregnancy rate and speed of
conception
Study gp : 88 women with
poor ovarian reserve
evidenced by inadequately
poor response toConclusion
OI
Control gp : 101 patients
selected for IVF
: DHEA
supplementation in women with
diminished
reserve,
DHEA 25mg TID for
3.7± 0.3 monthsovarianHad
IVF (microdose
independent of age,agonist/gn
leads to
max 450-600IU
increased, and more rapid,
62 had IVF, 9 had atleast one
prior OI, 17 missedconception rates Outcome –cumulative preg rate of 11 %
IVF cancellation rate 26 %
Miscarriages 44%
Outcome – Cumulative preg rate of 27%
IVF cancellation rate of 10%
Miscarriages 24%
Fertility and sterility vol 86,suppl 2,
sep 2006
DEHYDRO EPIANDROSTERONE (DHEA)
REPORTED REPRODUCTIVE BENEFITS
Improves egg/embryo numbers & quality
Spontaneous pregnancies
High IVF pregnancy rates
Shortens time to conceive
Cumulative pregnancy rates increases
Barad et al,j Assist.rep. Genet 2007
DOSAGE FOR USE IN INFERTILITY
• Administration of DHEA for 2 months 80µg/day
increased the level of DHEA to 544+/- 55µg
• Administration of DHEA ,four months prior to
IVF cycles increases the response of the ovaries
to gonadotrophin treatment and also improves
the overall outcome
Fertility and sterility sep 2005
DEHYDRO EPIANDROSTERONE (DHEA)
Dosage
- 25 mg three times a day
- Stay with DHEA till pregnancy
- Stop after pregnancy is confirmed
Is there a role in PCOS ?
• All patients with PCOS have increased
senstivity to androgens upto 70% have
elevated androgen levels and other 30% are
in the high normal range
• Hence initial conversion of DHEA to
androgens does not favour its use
in treatment of PCOS
DEHYDRO EPIANDROSTERONE (DHEA)
ROLE IN PCOs
Poorly responding PCOS
Where testosterone is decreased
Better response with DHEA
DHEA
OUTSIDE INFERTILITY
• Used in HSDD (100mg twice daily for 6 weeks )
• Increases the bone mineral density in
postmenopausal women
• Improving symptoms of depression, schizophrenia
and slowing the progress of Alzheimer’s diseases
• Treating SLE- Increased E2 and reduced DHEAS
levels in lupus patients may help induce cytokine
abnormalities early in disease
DHEA
1.HOW IS IT USED ?
2.WHEN IT IS ORDERED ?
• Concentrations of DHEAS are often measured, along with other hormones such
as FSH, LH, prolactin, estrogen, and testosterone, to help diagnose polycystic
ovarian syndrome (PCOS) and to help rule out other causes of infertility,
amenorrhea, and hirsutism
• It may be measured when a woman presents with signs and symptoms such as
amenorrhea, infertility, and/or those related to virilization. These changes vary
in severity and may include:
• A deeper voice
• Hirsutism
• Male pattern baldness
• Muscularity
• Acne
• Decreased breast size
• DHEAS levels may be ordered, along with other hormones, to investigate and
diagnose the cause of precocious puberty in young boys.
3.WHAT DOES THE TEST RESULT MEAN ?
• Normal DHEA and Androgens – adrenal gland
functioning is normal
a. In PCOS, DHEA is elevated or normal (b’coz primary androgens are
from ovaries )
b. Rarely it may be normal in adrenal tumors, when it is not secreting
the hormone
• Elevated level of DHEA – Adrenal tumors an increased
level of DHEA is not diagnostic.it usually indictaes further testing to
pinpoint the cause of hormonal imbalance
• Low level of DHEAhypopituitarism
adrenal dysfunction or
What dose is used?
• The following doses have been studied in scientific research:
In postmenopausal women and in elderly men: Doses of 25-50 mg
daily are commonly used
• For treatment of schizophrenia: Increasing doses of DHEA of 25 mg
OD for 2 weeks, 25 mg BD for 2 weeks, and 50 mg BD for 2 weeks
• For replacement of hormones when the adrenal glands are not
working well (androgen deficiency): 25-50 mg given daily as a single
dose
• For systemic lupus erythematosus (SLE): 200 mg per day along with
conventional medical treatment, but doses up to 600 mg per day
have been used
• For improving bone mineral density in people with weak bones
(osteoporosis): 50-100 mg per day
• For erectile dysfunction: 50 mg per day
DHEA
INTERACTIONS
Anastrozole (Arimidex)
Exemestane (Aromasin)
Insulin
Letrozole (Femara)
Medications changed by the liver (Cytochrome P450 3A4 (CYP3A4)
substrates)
Some medications changed by the liver include lovastatin (Mevacor),
ketoconazole (Nizoral), itraconazole (Sporanox), fexofenadine (Allegra),
triazolam (Halcion), and many others.
Tamoxifen (Nolvadex)
Triazolam (Halcion)
Medications for inflammation (Corticosteroids)- Decreases the effect of
DHEA
SIDE EFFECTS
•
•
•
•
•
Acne
Hair loss
Stomach upset
High blood pressure.
Some women can have changes in menstrual
cycle, facial hair growth, and a deeper voice after
taking DHEA
DHEA is UNSAFE when used in larger amounts
and long-term.
CONTRAINDICATIONS
DHEA supplementation is contraindicated in those with breast,
uterine, prostate and ovarian malignancy
Liver diseases
Pregnancy and breast-feeding
Hormone-sensitive conditions such as breast cancer, uterine cancer,
ovarian cancer, endometriosis, or uterine fibroids
Diabetes
Mood disorders
Polycystic ovary syndrome (relative)
Cholesterol problems
TAKE HOME MESSAGE
• Improves ovarian function especially in poor
responders
• Prohormone – helps in preparation of ovaries
before OI/ IVF
• Increase the quality of oocytes and average
embryo scores
• Increases the oocyte production in POF/POI
• Improves pregnancy outcome
• Decreases the rate of miscarriages