Related Experiment Video
Updated: Apr 1, 2026
Author Spotlight: Unveiling the Role of TMOD3 in Platinum Resistance and Immune Infiltration in Ovarian Cancer
Published on: August 2, 2024
The impact of oxaliplatin on the gonads: from bedside to the bench
Mattan Levi1, Ruth Shalgi1, Baruch Brenner2
1Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Study Hypothesis:
What is the impact of oxaliplatin on gonadal function?
Study Finding:
Our results in both the clinical and pre-clinical settings indicate that oxaliplatin exerts moderate transient gonadal toxicity.
What Is Known Already:
Recent studies have indicated a significant increase in survivorship of colorectal cancer patients of reproductive age, who may then face fertility concerns. The impact of oxaliplatin on gonadal function is yet to be discovered.
Study Design, Samples/Materials, Methods:
Eleven female (<43 years) and eight male (<45 years) patients recently diagnosed with colorectal cancer, who were candidates for oxaliplatin-based protocol, were enrolled into the study. FSH, estradiol, anti-Müllerian hormone (AMH) and menstrual pattern were measured in female patients, whereas FSH, inhibin-B, testosterone, and steroid-hormone binding globulin were measured in male patients. Hormones were measured at baseline and 6 months post-treatment (last chemotherapy administration) in men and women. In the animal model, pubertal mice were injected with oxaliplatin and sacrificed 1 week, 1 month and 3 months later. Ovarian reserve was estimated by serum AMH measurements. Testicular function was evaluated by serum inhibin-B and sperm evaluation. Gonadal apoptosis (TUNEL), proliferation (Ki-67), repair (PCNA), ovarian reserve (AMH) and testicular reserve (DAZL) were measured by immunohistochemistry.
Main Results And The Role Of Chance:
In all women, AMH decreased post-treatment, but remained above the detection limit in 9/11 patients (P < 0.05). FSH was elevated, but did not exceed the premenopausal range in 9/11 patients. All patients remain menstruating or resumed menstruation post-treatment. In female mice oxaliplatin induced transient apoptosis at 1-month post-treatment. In men Inhibin-B was slightly reduced post-treatment. In male mice oxaliplatin did not affect spermatozoa concentration, but was associated with transient, moderate reductions of spermatocytes-spermatogonia numbers and spermatozoa motility.
Limitations, Reasons For Caution:
Future prospective large-scale studies are warranted in order to affirm these outcomes.
Wider Implications Of The Findings:
Due to high survival rates of colorectal cancer patients of reproductive age that were diagnosed at early stages of the disease, the issue of treatment-induced gonadotoxicity gains significance. Since at the individual level there might be a risk of infertility, a detailed discussion and referral to fertility preservation prior to initiation of treatment is recommended. Nevertheless, oxaliplatin-based protocols appear to be less gonadotoxic than other chemotherapeutic protocols.
Large Scale Data:
None.
Study Funding And Competing Interests:
This study was supported by the Israeli Science Foundation (ISF) grant 13-1816 (I.B.-A.). There is no conflict of interest.
Insights
Oxaliplatin causes moderate, temporary damage to gonadal function in colorectal cancer patients. Fertility preservation discussions are recommended before treatment due to potential infertility risks.
Area of Science:
- Oncology
- Reproductive Endocrinology
- Pharmacology
Background:
- Colorectal cancer survivorship is increasing in reproductive-aged individuals.
- Fertility concerns are a significant issue for these patients.
- The specific impact of oxaliplatin on gonadal function requires further investigation.
Purpose of the Study:
- To evaluate the impact of oxaliplatin on gonadal function in colorectal cancer patients.
- To assess both clinical and pre-clinical effects of oxaliplatin on reproductive health.
Main Methods:
- Enrolled 11 female and 8 male colorectal cancer patients undergoing oxaliplatin treatment.
- Measured key reproductive hormones (FSH, AMH, estradiol, inhibin-B, testosterone) at baseline and 6 months post-treatment.
- Utilized a pre-clinical mouse model to assess ovarian and testicular toxicity, apoptosis, proliferation, and reserve.
Main Results:
- In women, anti-Müllerian hormone (AMH) decreased, but remained detectable in most patients; FSH elevated within premenopausal ranges, and menstruation was preserved.
- In men, inhibin-B showed a slight reduction.
- Animal models showed transient gonadal apoptosis and moderate reductions in spermatogonia and sperm motility post-oxaliplatin exposure.
Conclusions:
- Oxaliplatin exhibits moderate, transient gonadal toxicity.
- Referral for fertility preservation discussions is crucial before initiating oxaliplatin-based chemotherapy.
- Oxaliplatin-based protocols may be less gonadotoxic compared to other chemotherapy regimens.
Related Concept Videos
02:07Oogenesis
01:24Gonadal and Placental Hormones
In males, testosterone is the primary gonadal androgen. It plays a central role in the maturation of male reproductive organs — the penis and testes. Additionally, testosterone is instrumental in the development of secondary sexual characteristics — a deep voice as well as facial and pubic hair...