GnRH analogues for prevention of premature ovarian failure

Various glomerulonephritides unfortunately often require treatment with chemotherapeutic agents, such as cyclophosphamide. A potential adverse effect of these agents in females of child-bearing age, is premature ovarian failure. Nate previously posted about this. Since then, there have been a couple of papers published that address this dilemma further.


A meta-analysis of six randomized controlled trials reported that GnRH treated women had a higher odds of return of spontaneous menstruation than those not treated (OR 3.46; 95% CI 1.13 – 10.57), but this did not translate into a significant difference in the rate of spontaneous pregnancy after chemotherapy. However, many people are cautious in the interpretation of these results, given the small sample size in the trials, heterogeneity of protocols and varying follow-up times.




More recently, a randomized trial of triptorelin vs standard care in women with breast cancer was published. This study, performed in Italy, randomized 133 women to GnRH and 148 to standard care. Subjects were reviewed one year after the last cycle of chemotherapy for occurrence of early menopause (defined as no resumption of menstrual bleeding and postmenopausal levels of FSH and estradiol one year after cessation of chemotherapy).
The rate of early menopause was 25.9% in standard care vs 8.9% in the GnRH group (p for difference <0.001).


Whilst encouraging, these findings must be tempered by the fact that recovery of menses does not directly translate to fertility (limited data was available for this cohort at the time of publication). Furthermore, the chemotherapeutic regimens used, dosing and the duration of treatment make it hard to generalize the findings to a ‘nephrology disease’ population. There are alternative methods available, with somewhat stronger recommendations from experts in the field – these include embryonic cryopreservation.

HCG in Kidney Disease

That cardiac biomarkers, including Troponin and BNP, can be elevated in CKD or ESKD without necessarily having clinical significance is familiar to most of us. Whether you believe that an elevated Troponin in ESKD is due to diminished clearance or some constant low-level myocardial damage of unclear significance, most would be comfortable dismissing borderline positive results without suggestive signs or symptoms.

Recently I was asked an interesting question pertaining to pregnancy testing in CKD and ESKD. A dialysis patient had a serum HCG level that was borderline positive. The patient and her physicians wanted to know whether this could be a false positive related to her kidney disease or whether she may in fact be in the first weeks of a pregnancy. After searching the literature and conferring with my OB colleagues, here is what I found:

Here is a case report and a nice review of the topic. Not surprisingly HCG levels can be falsely elevated in CKD, though for quite a variety of reasons. These include decreased clearance of HCG, increased levels of other gonadotropins that cross react with the HCG assay, including LH and FSH, as well as other cross-reacting substances including cold agglutinins and heterophile antibodies.

How to distinguish? The urine HCG assay does not cross-react with these substances, and so, if the patient still makes urine, confirmatory testing with urine HCG is a reasonable first step. In ESKD patients who no longer make urine, progesterone levels can be used as a next step especially when more immediate knowledge of pregnancy status is required. If progesterone is low, viable pregnancy is unlikely, though serial serum HCG levels should be monitored to rule out non-viable pregnancy (egs, ectopic). If there is no urgency to determining pregnancy status, follow-up serum HCG to see if doubling occurs at expected intervals should be performed. In my patient's case, her serum HCG level one week later was the same as that one week prior, and the serum HCG was deemed to be elevated due to decreased clearance in ESKD.