DEHYDROEPIANDROSTERONE (DHEA)

DR.T.RAMANIDEVI MD DGO FICS FICOGDIRECTOR, JANANI FERTILITY CENTRERAMAKRISHNA 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 DHEASANDROSTENEDIONE

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/ AlzhiemersObesityType II DMImmune dysfunctionAutoimmune diseaseCancer

DEHYDRO EPIANDROSTERONE (DHEA)Low levels of DHEA is associated with Depression Loss of well being CVS problems Osteoporosis Erectile dysfunction Low libido

• Infertility

DHEA

1.DHEA TO IMPROVE OVARIAN FUNCTION1.DHEA TO IMPROVE OVARIAN FUNCTION

Reprod Biomed Online. 2009 Oct;19(4):508-13.

2.Pre conditions the ovary for 2.Pre conditions the ovary for ovulation inductionovulation induction

FERTILITY AND STERILITY SEP 2005

ACTION OF DHEAS

PROHORMONE IMPROVES

REDUCES OVARIAN APOPTOSIS RESERVE

IMPROVES AUGMENTS OVARIAN IGF -1

ENVIRONMENT

DHEA

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 AGEINGTESTOSTERONE EVALUATED

• UPPER 1/3 OF NORMAL

• NO DHEA

• LOW 2/3 OF NORMAL

• DHEA GIVEN

3.ROLE IN POF/POIIncrease 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 4.Reduces IVF cancellation ratesrates•DHEA supplementation shows increase in

IGF1 concentrations to potentiate gonadotrophin action in women with diminished ovarian reserves

•Increase in average embryo scores per oocyte in IVF cycle outcomes and reduces IVF cancellation rates

•DHEA supplementation facilitates gonadotrophins effect, it also reduces the dose of gonadotrophins in IVF cycles

Human reproductions sep 2006

Hum Reprod. 2010 Oct;25(10):2496-500. Epub 2010 Aug 21.

Hum Reprod. 2000 Oct;15(10):2129-32.

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 rates5.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 outcomeFertility 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

Control gp : 101 patients selected for IVF

Study gp : 88 women with poor ovarian reserve evidenced by inadequately poor response to OI

Had IVF (microdose agonist/gn max 450-600IU

Outcome –cumulative preg rate of 11 % IVF cancellation rate 26 % Miscarriages 44%

DHEA 25mg TID for 3.7± 0.3 months

62 had IVF, 9 had atleast one prior OI, 17 missed

Fertility and sterility vol 86,suppl 2, sep 2006

Conclusion : DHEA supplementation in women with diminished ovarian reserve, independent of age, leads to increased, and more rapid, conception rates

Outcome – Cumulative preg rate of 27% IVF cancellation rate of 10% Miscarriages 24%

REPORTED REPRODUCTIVE BENEFITSImproves 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

DEHYDRO EPIANDROSTERONE (DHEA)

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 usein treatment of PCOS

ROLE IN PCOs

Poorly responding PCOS

Where testosterone is decreased

Better response with DHEA

DEHYDRO EPIANDROSTERONE (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 normala. 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 DHEA- adrenal dysfunction or hypopituitarism

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