Ovarian stimulation and ovarian cancer
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Ovarian Stimulation and Ovarian Cancer . Bilgin GURATES, MD. I nfertility. 1% of US infants born in 2004 with ART In the United States nearly doubling between 1973 and 1991. ovulation-inducing drugs on cancer risk.

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Ovarian stimulation and ovarian cancer

Ovarian Stimulation and Ovarian Cancer

Bilgin GURATES, MD.


I nfertility

Infertility

  • 1% of US infants born in 2004 with ART

  • In the United States nearlydoubling between 1973 and 1991.


Ovulation inducing drugs on cancer risk

ovulation-inducing drugs on cancer risk

  • A number of investigations have attempted to address thelong-term effects of ovulation-inducing drugs on cancer risk,but most have had shortcomings.

    • small numbersof study subjects,

    • short follow-up times,

    • impreciseinformation on drug exposures and the indications for usage,

    • absence of information on other correlates of drug exposurethat could influence cancer risk.


Ovulation inducing drugs

Ovulation-inducing drugs

  • CC, in usesince the 1960s

  • hMG in usesince the 1960s

  • hCG have been used since 1932


Inconsistent information

inconsistent information

  • Increasedrisk of ovarian cancer

    • Rossing MA,NEnglJMed. 1994

    • Whittemore AS, Am J Epidemiol1992

  • No associationof ovarian cancer

    • Brinton LA, ObstetGynecol. 2004

    • Rossing MA,Am J Epidemiol. 2004

  • Increased risk of breast cancer (CC)

    • Lerner-Geva L, Breast Cancer Res Treat. 2006

    • Brinton LA,Hum Reprod.2004

  • Reduced riskof breast cancer (CC)

    • Jensen A,Cancer Epidemiol Biomarkers Prev. 2007

    • Venn A,Lancet. 1999


  • Background

    BACKGROUND

    • Three lines of evidence raise concern regarding potentialeffects of ovulation-inducing drugs on cancer risk.

      • 1. Mostcommonly used medications,

        • clomiphenecitrate andgonadotropins

        • in the etiology of both breast and ovariancancers

    • 2. E2 and P levels

    • 3. Someclinical and epidemiological studies


    I nfertility c ancers

    Infertility/Cancers

    • Anovulation, has been linked increased risks of

      • Endometrial and (Coulam CBObstet Gynecol 1983)

      • Possiblybreast cancers (Modan B, Am JEpidemiol 1998)

  • Other causes of infertility have also been related to the risks of subsequent cancers:

    • endometriosis to

      • ovarian (Borgfeldt CActa Obstet Gynecol Scand2004)

      • Breast(Brinton LAAm J ObstetGynecol 1997) cancers

    • tubal factor to

      • ovarian cancers (Ness RBAm J Epidemiol 2003).


  • Cancers

    CANCERS

    • Ovarian cancer

    • Breast cancer

    • Uterine cancer

    • Malignant melanoma

    • Non-Hodgkin lymphoma

    • Other Cancers

      • Cervicalcancer

      • Thyroid cancer

      • Persistenttrophoblastic tumors

      • Colon cancer


    Ovarian cancer

    OVARIAN CANCER

    Rossing MA, 1994

    Modan B, 1998

    Venn A, 1999

    Klip H, 2002

    Doyle P, 2002

    Brinton LA,2004


    Ovarian cancer1

    OVARIAN CANCER


    In summary

    InSummary

    • Ovulation-stimulating drugs mightpreferentially affectthe risk of borderline ovarian tumors is also suggested byseveral studies.

    • Based on the evidence to date, there is no conclusive linkbetween fertility drug use and ovarian cancer.

    • However,most of the studies have had relatively small numbers and/orshort follow-up.

    • Specificattentionshouldalso be focused on effectsamongwomenwhoremainnulligravid.


    Breast cancer

    BREAST CANCER


    Ovarian stimulation and ovarian cancer

    BREAST CANCER


    Ovarian stimulation and ovarian cancer

    BREAST CANCER

    InSummary

    Studiestodatehave shown both decreases as well as possible increases in risk.

    Additional studies that can account for effects of otherrecognized risk factors (including delays in fertility) should be undertaken.


    Endometrial cancer

    ENDOMETRIAL CANCER

    Twofold increase

    Nonsignificant increase

    (RR 1.8; 95% CI, 0.9 –3.3)


    Melanoma

    MELANOMA

    The available evidence does not allow any conclusions

    regarding this association. Further study may be warranted.


    Non hodgkin lymphoma

    Non-Hodgkin lymphoma


    Other cancers

    OTHER CANCERS

    • Cervicalcancer

      • Clomiphenewas reducedrelative to nonusers (RR 0.4; 95% CI, 0.2– 0.8),

  • Thyroid cancer

    • In a pooled analysis of 13 case-controlstudies from North America, Asia, and Europe, use of fertilitydrugs was found to be associated with a 60% increasein thyroid cancer risk (95% CI, 0.9 –2.9) [La Vecchia, 1999]

    • Asignificant four-fold excess risk associated with useof fertility drugs [Kolonel LN, 1990]

  • Persistenttrophoblastic tumors

    • no additional risk

  • Colon cancer

    • no relationship to fertility drugs


  • Thank you

    THANK YOU


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