interesting question.Thank you for your detailed information.
It sounds like you have had a very thoughtful and in depth evaluation.
Ovarian vein sampling is, I believe , the most high tech test we have for sorting out where the testosterone is coming from.
definitely, taking out the ovaries would be the next step.
The question you should ask your reproductive endocrinologist is whether an ovary that contains a testosterone producing tumor will be able to produce a viable egg for pregnancy.
In general testosterone producing tumors can be malignant such as a sertoli leydig cell tumor. There is a benign condition called stromal hyperthecosis where testosterone is produced. I don't think it usually produces this much. An endocrinologist would know for sure.
I suppose another option would be to undergo a laparoscopy and have biopsies of the ovaries. The risks of that approach would be: could have bleeding requiring the removal of the whole ovary, cause scarring and infertility, or missing the actual lesion in the ovary.
Finally, unrelated to the testosterone, you should ask your reproductive endocrinologist what are the realistic odds of fertility at age 40. How good are your eggs? Many women donot have enough "egg power" and look into donor egg options.
please let us know what happens
Thank you for the update.I actually circulated around your question to my smart reproductive endocrinology colleagues at Mass General Hospital. Here are some comments so far
From Dr Jan Shrifren
These T levels are quite high, but appears she has had an extraordinarily thorough evaluation and no evidence of an ovarian or adrenal tumor. Would not advise oophorectomy unless childbearing were complete and hyperandrogenic symptoms were not controlled with medical management. Certainly not necessary and would delay childbearing even further, but for reassurance, OCPs and/or a trial of ovarian suppression w/ Lupron w/ estrogen (OCP) add-back should result is significant reductions in T levels.
Unfortunately, fertility at age 40 is never great, but high estrogen levels associated w/ ovarian hyperstimulation likely will reduce circulating free androgens. A pure FSH protocol would be preferable.
Interested in the thoughts of my fellow REIs, but see no clear reason she should not initiate fertility treatment and keep those precious ovaries!
from Dr Thomas Toth:
I would want to make sure she has had 17OHP to eliminate late onset congenital adrenal hyperplasia ( probably done if seeing endocrinologists for more rare etiologies). My first thought is stromal hyperthecosis and would want to make sure she was not insulin resistant and benefit from metformin therapy. I am sure the remainder of smarter colleagues will have thoughts and suggestions we can consider as well before making surgical decision
another of my great colleagues has commented:
Dr Aaron Styer:
Thank you for considering us in this extraordinary case. I am also impressed by the comprehensive evaluation that this woman has received. I am in complete agreement with Jan regarding not performing bilateral oophorectomy unless childbearing complete or hyperandorgenic symptoms not controlled by medical therapy. Unfortunately, the literature contains conflicting data regarding the utility of Lupron or OCP suppression of pituitary LH to exclude androgen producing ovarian tumor. Many of these tumors can be dependent on LH, just as theca cells are for steroidogenesis. To this end, suppression of testosterone during pituitary downregulation may not be reassuring to exclude an androgen producing tumor.
In lieu of an obvious ovarian mass, she should proceed with the assistance of a reproductive endocrinologist to expedite her course to conception given age and uncertain reason for excessive ovarian androgen production. Unfortunately, as you know, some of these tumors may not ever be visualized as they can be located in the ovarian hilum (Leydig cell tumor). After childbearing completed, there are some reports of initial elective laparoscopic unilateral oophorectomy to confirm presence of tumor if bilateral elevated T, then followed by removal of contralateral ovary if tumor confirmed in first ovary.
Finally got better info on results from ovarian vein sample. It's a little different from how I depicted (confusion in phone/verbal conveyance of numbers) and has 2 additional figures I didn't have originally.
Distal Vena Cava: 514
LOV vein: 314
ROV vein origin: 317
Proximal Inferior vena cava: 789
They couldn't get 100% into the R ovarian vein and had to go with a spot a bit "back" from truly in the vein is my understanding. So, both ovaries are actually producing similar levels of testosterone. I also saw a medical endocrinologist (vs reproductive one) yesterday and she's running various tests to try to see if this could be Cushing's or any other endocrine/thyroid/pituitary based causes. She also mentioned possibility that perhaps my PCOS-related insulin issues might have triggered ovarian cells to shift to the testosterone production somehow. Overall though, she seemed to be echoing the gynecological oncologist, that with no visual tumors on scans, issues occurring on both sides simultaneously, and now given both sides seem "equal" in their production....seems doubtful it is tumor or cancer-driven.
Investigation continues, and if tumor/cancer issues circle back I'll be sure to update here!
Thank you, Dr. Goodman, for your insights.
Investigation is still ongoing and yes, I'm blessed to have what seems to be a good team of physicians trying to figure it out. Indeed, the ovarian sampling seems cutting edge! No radiologist in my area had any experience with it, and I believe it was a new/rare procedure for the one who did it (required traveling on my part to the Washington DC area).
This issue was discovered prior to Day 3 testing and efforts to test my egg quality & quantity. Initial discussions are that this high a testosterone level makes even harvesting viable eggs out of the question, and the extended time with xposure to excess androgens could have affected quality of any eggs I have.
Perhaps the oncologist (we are still awaiting a final gameplan from him) will go the route of biopsies as you mention. So far I'm not able to find anything that really addresses whether having a testosterone-secreting tumor in both ovaries simultaneously actually would make it likely its something besides tumors and a general endocrinology issue (I see a medical endo this week for that testing).
I will definitely keep the thread updated as I know my situation isn't super common and hopefully the info will help someone else too.
Thanks, and have a great holiday!
Wow. Thanks so much Dr. Goodman and colleages! Your help is appreciated and provided some great additional information and viewpoints - I'll share this thread with my RE also.
I am indeed insulin resistant along with a family connection to insulin issues (maternal grandfather juvenile diabetes, maternal aunt hypoglycemic, me PCOS/IR); I know the endocrinologist is checking further into that in bloodwork being done tomorrow based also on her point about insulin perhaps driving triggering the cells to produce testosterone somehow. Also doing 24 hour urine collection and more bloodwork on typical endocrine type items such as FSH/LH, DHEA, DHEAS, and so forth. Metformin is something she seemed to feel was in my future on top of the discussions already had about it being definitely something for conception treatment given PCOS.
Hyperthecosis is one of the phrases I know my RE has mentioned also so I think that's being considered in the testing and investigation.
The medical reduction methods and conception course items are not yet something we've stepped into yet, thought I'll be sure to discuss with my RE to see if that is a step planned once and if general endocrine drivers are ruled out in my case.
Thanks so so much!
Just an update: My case is being referred to NIH by my repro endo after her review of info I provided along with extensive discussions amongst her practice's colleages. She mentioned that including review of the information you and your colleages provided, so thank you again for your time and responses.
I won't have my appoint there til next month; meanwhile results of testing and further input from the general medical endocrinologist are still pending.
thank you for the update
please keep us posted