28 replies to this topic

[fola]

I think that restriction is only if you're over 35 and a smoker.  This increases the risk of blot clots and other heart issues.  Either way, for the most part, BC pill are generally considered safe. 

[fola]

I'm going to tell my docs about what your doc told you.  Personally, I've been freezing, sluggish and puffy since starting TKIs, but every time they tested my thyroid, it came out in the low-normal range.  Sounds a lot like what was happening to you.  Thanks for the info Beth. 

[fola]

Hi all,

An important update.  I got the results of my recent full spectrum hormone levels and everything was normal except my FSH which was very high.  Basically, it looks like Gleevec is pushing me into menopause which should be at least 20 to 25 years down the road.  I've only ever been on a 400 mg dose of Gleevec for the past 2.5 years.  However, from what I've read, it looks like increased dosage or continued long term usage can cause premature ovarian failure. 

This is extremely depressing news.  I keep trying to get use to being sick and maybe having a somewhat normal future, but it seems like there's always bad news.  I've read through posts here and on several other forums and it seems that we women are all having the same problems.  I.e. heavy periods, inconsistent periods, weight gain, bloating and wonky hormones.

From reading through some research papers, it appears that the blocking of cKit may be primarily responsible for disrupting endocrine related reproductive hormones in both men and women.

I'm not sure what to do.  I really didn't think I'd have to start worrying about menopause, osteoporosis (due to premature menopause) and increased risk of heart disease for at least a couple decades.  I guess I was wrong.

I feel like my whole life passed me by and I never got to experience it. 

I'm just a bag of impotent rage with no outlet.

[pammartin]

Hi Fola,

I haven't looked into the research concerning this thread in detail because I am past this stage, but I wonder if the CML does not have some effect on early menopause also.  I have spoken with a few women who are around my age and had no signs of menopause then when the CML began cooking it seemed to throw our bodies into an early menopause, even before the TKI's were introduced to the body.  I am interested in the research you have found and reviewed, would you mind providing links to a few of the papers you mentioned?  I will go back and read through the thread and make sure I didn't miss ones you might have already posted.  I will not insult you or any other who is facing the possibility of early menopause by stating I know how you feel, because I do not.  Some times there seems no end to the side effects, symptoms, ongoing problems, and negative evidence we face taking these drugs, that part I can relate too, in some way they touch us all.  Find an outlet to push that rage into, because held in it will wreck havoc throughout your system, adding to your other difficulties.   You are far more than a bag, you feel, and that is the hardest part of being human.

[fola]

Hi Pam,

Pre-official diagnosis, they ran every test on me they could think of, including endocrine level tests.  I tested normal every time.  Aside from the CML, my hormonal system appeared to be functioning normally with no elevations or physical symptoms related to reproductive or hormonal imbalances.  So as I started Gleevec, that changed.  Heavier longer periods, extreme cyclical bloating, heavy cramping, lower back pain, weight gain, inability to lose weight (no matter how much I exercised or how little I ate - I even kept a detailed journal).  My docs had been testing my FSH levels and they have been increasing since starting Gleevec.

I think some think that early menopause may be linked to CML because the average age of female patients tend to be around menopausal years or older, however, for most of us, I don't think this is the case.  I just don't understand why my doctors did not warn me of this possibility.  I think they should have been monitoring FSH levels in all younger women on this drug.  I had to ask for the test because I kept complaining that I felt "out of sorts."

Here are some links with some info:

Papers

Primary Ovarian Insufficiency Associated with Imatinib Therapy - N Engl J Med 2008;  358:1079-1080: http://www.nejm.org/...56/NEJMc0707841

More on Ovarian Insufficiency with Imatinib - N Engl J Med 2008;  358:2648-2649: http://www.nejm.org/...056/NEJMc080707

Gynecomastia during imatinib mesylate treatment for gastrointestinal stromal tumor: a rare adverse event: http://www.biomedcen...230X-11-116.pdf

Effect of Imatinib on Human Luteinized Mural Gran-Ulosa Cell Viability: http://epub.theoncol...issue/49503/141

Endocrine side effects of broad-acting kinase inhibitors: http://erc.endocrino.../17/3/R233.full

The Obstetric Hematology Manual (2010) (pg. 247) "

Articles

Gleevec May Disrupt Ovarian Function: http://abcnews.go.co...=4510687&page=1

Blog Posts - many women all over the world have similar complaints.

Gleevec linked to Menopause: http://www.cmlsupport.org.uk/node/5700

Pre-menopause: http://www.cmlsupport.org.uk/node/5679

For the Gals: http://talkbloodcanc...ode/1320?page=1

Fertility in Women Diagnosed with CML: http://preservationo.../fertility-cml/

http://epub.theoncol...issue/49503/141

[fola]

Also forgot to point out that the above link to the Gynecomastia paper reported increased FSH levels in men who were being treated with Gleevec for GIST.  So increased FSH levels are not just a problem for women.

[Pin]

Fola, I'm so sorry to hear this - it seems as though just when we think we might just have things under control something like this happens I want to thank you also for sharing your story - I have a number of the symptoms you've listed so I will be asking my doctor about this, it's obviously a really important issue for you and all of us and there are other young women our age on this site who this is very relevant to so it is good when we can share our experiences for both information and support. I hope you have someone you can talk with and please do come on here as well. Big hugs - Pin xxx.

[fola]

Thanks Pin and everyone for their support.  For me, this forum has been a life line.  CML is rare enough and it is especially rare among younger patients.  Most of the times our doctors don't know what to do with us.  I really don't think I'm unique in this occurrence.  I think a lot of doctors don't test women (or men) for FSH if they are under a certain age and are not on traditional chemo.  Personally,  I think this is a mistake.  Especially considering all of our similar symptoms.

I'll be seeing a round of specialists soon to figure out what to do.  Aside from fertility, Premature Ovarian Failure (Ovarian Insufficiency) has a huge impact on our general health.  I.e. bone density, heart health, etc.  No one knows whether TKI induced POF/OI is reversible with TKI cessation, but considering that we're expected to stay on these drugs for life, it may not matter. 

[fola]

Hi all,

Found a paper from 2011 confirming that Gleevec (Imatinib) most likely does cause ovarian malfunction.  Both Dr. Druker and Dr. Mauro are authors on this paper.  Very interesting read concerning a 17 year old girl. 

http://theoncologist.alphamedpress.org/content/16/10/1422.abstract

Will Imatinib Compromise Reproductive Capacity?

1. Alberuni M. Zamah
   
   

   ^a

   ,
2. Michael J. Mauro
   ^b
   ,
3. Brian J. Druker
   ^b
   ,
4. Kutluk Oktay
   ^c
   ,
5. Merrill J. Egorin
   ^d
   ,
6. Marcelle I. Cedars
   ^a
   and
7. Mitchell P. Rosen ^a
8. ^aUCSF Medical Center, Center for Reproductive Health, San Francisco, California, USA;
9. ^bOHSU Medical Center, Knight Cancer Institute, Portland, Oregon, USA;
10. ^cNew York Medical College, Institute for Fertility Preservation, Valhalla, New York, USA;
11. ^dUniversity of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA
12. Correspondence: Mitchell P. Rosen, M.D., UCSF Center for Reproductive Health, UCSF Medical Center, Department of Obstetrics, Gynecology and Reproductive Sciences, Division of Reproductive Endocrinology and Infertility, San Francisco, California 94122, USA. Telephone: 415-353-7475; Fax: 415-353-7744; e-mail: RosenM{at}obgyn.ucsf.edu

• Received April 18, 2011.
• Accepted July 20, 2011.
• First published online in THE ONCOLOGIST Express on September 23, 2011.

• Disclosures: Alberuni M. Zamah: None; Michael J. Mauro: None; Brian J. Druker: Research funding/contracted research: Institution receives funding from Novartis for clinical trials; Kutluk Oktay: None; Merrill J. Egorin: None; Marcelle I. Cedars: None; Mitchell P. Rosen: None.

  The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. No financial relationships relevant to the content of this article have been disclosed by the independent peer reviewers.

Abstract

Imatinib mesylate is the first in a family of highly effective, minimally toxic, targeted agents used widely to treat Philadelphia-positive leukemias and selected other cancers, leading to a steady rise in the prevalence of patients using such therapy. Because failure of therapy would require conventional gonadotoxic chemotherapeutics, many female patients using imatinib may choose to preserve fertility. Herein, we provide evidence of a potential negative effect of imatinib on ovarian function by reporting the first case of a woman who showed a severely compromised ovarian response to gonadotropin stimulation while on imatinib, with a normal ovarian response after stopping this medication.