Reproductive and Sexual Sequelae of Neuroendocrine Tumour Therapies

Review finds chemotherapy has proven fertility harm in NET patients, while somatostatin analogues appear relatively safe — but data on sexual function is nearly absent

Journal: Endocrine-related Cancer | Published: 2026-04-15 | Type: Review | PMID: 41921030 Authors: Shekhda KM, Shah PM, Biddanda A, Grossman A, Caplin M — Neuroendocrine Tumour Unit, ENETS Centre of Excellence, Royal Free Hospital, London; UCL Hospital; London North West University Healthcare NHS Trust Funding/COI: Not listed for either

Summary

Neuroendocrine tumours (NETs) are slow-growing cancers increasingly diagnosed in younger patients, yet the reproductive and sexual consequences of their treatments have been almost entirely ignored in the literature. This review synthesizes what little data exists across four treatment classes: somatostatin analogues (SSTAs), everolimus/sunitinib, peptide receptor radionuclide therapy (PRRT), and chemotherapy. The headline finding is a vacuum: for most NET therapies, fertility and sexual function data are so sparse the authors can barely draw conclusions.

Claims

• Chemotherapy: Well-established gonadotoxicity; the review endorses fertility preservation counseling before initiation — the only concrete, evidence-backed recommendation in the paper
• Somatostatin analogues (octreotide, lanreotide): No strong evidence of fertility harm; multiple reported pregnancies during SSTA treatment with generally favorable maternal and fetal outcomes
• PRRT (lutetium-177 DOTATATE): Gonadal effects poorly characterized; the radionuclide component raises theoretical gonadotoxic concern but clinical data are insufficient to quantify
• Molecular targeted therapy (everolimus, sunitinib): Fertility impact "as yet poorly defined"; animal data suggest harm but human reproductive outcomes are not well studied
• Sexual dysfunction: Data described as "very limited" across all NET therapies
• Receptor expression: NETs can express estrogen receptors (ER), progesterone receptors (PR), and testosterone receptors (TR); the authors flag this as a reason to test tumor tissue for receptor status before initiating hormonal therapy for sexual dysfunction — but note this recommendation "warrants additional studies"

Study Quality

This is a narrative review, not a systematic review or meta-analysis — no PRISMA flow, no predefined inclusion criteria, no pooled statistics. The authors summarize existing literature across four drug classes and two endpoints (fertility, sexual function), but the evidentiary base they are summarizing is itself weak: small case series, animal studies, and indirect inferences from oncology toxicity data. No sample sizes, effect sizes, or p-values appear in the abstract, which is consistent with a paper that found there is very little to synthesize.

The review is authored from a specialist NET center (Royal Free, ENETS-accredited), which lends clinical credibility. However, without a documented search strategy or explicit quality appraisal of included studies, it functions more as an expert opinion piece with citations than a rigorous evidence synthesis.

Red Flags

• No declared funding source or conflict of interest statement — unusual for a review paper and an immediate credibility question given that somatostatin analogues are expensive branded drugs with significant commercial interest
• Narrative review format means cherry-picking of favorable SSTA pregnancy outcomes cannot be ruled out
• The "many patients have conceived successfully" framing on SSTAs is anecdotal — no denominator, no comparison group, no definition of "many"
• ER/PR/TR receptor-status recommendation is speculative: the authors themselves say it "warrants additional studies," so the mechanism linking NET receptor expression to treatment response for sexual dysfunction is unestablished
• No quantitative data whatsoever in the abstract — every claim is directional, not numerical

Strengths

• Fills an acknowledged gap: reproductive sequelae in NET patients are genuinely understudied, and naming that gap has value
• Covers both male and female patients, and addresses both fertility and sexual function rather than conflating them
• The chemotherapy fertility harm point is well-supported in broader oncology literature even if NET-specific data are thin
• Clinical setting (ENETS Centre of Excellence) means authors have real patient exposure to the problem they are describing

Verdict

This review is a well-intentioned acknowledgment that a literature gap exists, not a paper that closes it. Its value is largely rhetorical: it makes the case that researchers should study this. For a reader wanting numbers — what proportion of PRRT patients experience gonadal failure, what is the magnitude of SSTA's effect on testosterone, how common is sexual dysfunction post-everolimus — this paper offers almost nothing. The absent funding and COI disclosures are a legitimate concern in a review covering branded somatostatin analogues. File it as a signpost pointing to an unstudied problem, not as evidence for any clinical conclusion.