Benefits and drawbacks of hormonal treatment/orchidopexy

Guy Bogaert

UZ Leuven KULeuven Dept of Urology, Herestraat, 49, B – 3000, Leuven, Belgium.

Correpondence; Prof Dr med. PhD em. Guy Bogaert Herestraat, 49, B – 3000, Leuven, Belgium.

Table of contents

Abstract
Résumé
Paper
References
Author

Abstract

Cryptorchidism is a symptom with multifactorial etiologies that range from endocrine signaling failure and epididymo-gubernacular mechanics to primary testicular dysgenesis. In contemporary practice, surgical orchidolyse and orchidopexy is standardized and widely successful at placing the testis in its normal scrotal environment; however, hormonal therapy remains controversial. This paper synthesizes translational and clinical evidence—including guideline positions, randomized trials, meta-analyses, long-term cohort data, and biopsy-based histology—to appraise the benefits and drawbacks of (1) primary hormonal treatment and (2) adjunctive hormonal therapy after successful orchidopexy, alongside (3) the benefits and limitations of orchidopexy itself. Special attention is given to fertility-relevant endpoints (Ad spermatogonia, inhibin B, semen analysis) and real-world outcomes such as paternity.

We conclude that primary hormonal therapy should not be used to induce descent, but carefully selected, low-dose, intermittent GnRH analog therapy after orchidopexy may benefit germ-cell maturation in boys with congenital true cryptorchidism and boys with bilateral ascending cryptorchidism and proven histological low fertility potential, whereas orchidopexy—performed expertly and early (ideally ≤12–18 months)—remains the gold standard for durable scrotal positioning, improved testicular growth trajectories, and facilitation of surveillance. The decision to offer adjuvant hormonal therapy should be individualized, biopsy-informed when feasible, and framed by shared decision-making about uncertain long-term fertility gains.

Key words Cryptorchidism hormonal treatment orchidopexy

Résumé

La cryptorchidie est un symptôme à étiologies multiples, incluant des défauts de signalisation endocrinienne, des anomalies épididymo-gubernaculaires et une dysgénésie testiculaire primaire. Si l’orchidolyse et l’orchidopexie sont aujourd’hui standardisées et efficaces pour rétablir la position scrotale, l’utilisation d’un traitement hormonal demeure controversée. Cette synthèse évalue, à partir de données translationnelles et cliniques (recommandations, essais randomisés, méta-analyses, cohortes à long terme, histologie testiculaire), les bénéfices et limites de (1) la thérapie hormonale primaire, (2) la thérapie hormonale adjuvante après orchidopexie réussie, et (3) l’orchidopexie elle-même. Une attention particulière est portée aux critères de fertilité (spermatogonies Ad, inhibine B, analyses de sperme) ainsi qu’aux résultats réels tels que la paternité. Les données disponibles indiquent que la thérapie hormonale primaire ne doit pas être utilisée pour induire la descente, mais qu’un traitement adjuvant par agoniste de la GnRH, à faible dose et de façon intermittente, peut améliorer la maturation germinale chez des garçons soigneusement sélectionnés présentant un faible potentiel de fertilité. L’orchidopexie précoce (≤12–18 mois) demeure toutefois la référence pour garantir une position scrotale durable, des trajectoires de croissance testiculaire favorables et une surveillance adéquate. L’indication d’une thérapie hormonale adjuvante doit être individualisée, idéalement éclairée par la biopsie, et discutée dans un cadre de décision partagée en raison de bénéfices fertiles à long terme encore incertains.

Mots-clés: traitement hormonal, cryptorchidie orchidopexie

Open slides

Introduction and standpoint

As pediatric urologists, we try to “mimic nature,” restoring a testis to its intended scrotal niche and supporting its maturation. Yet cryptorchidism is not a single disease: it is a final common phenotype produced by varied upstream defects—endocrine (e.g., impaired mini-puberty), mechanical (e.g., epididymo-gubernacular interface and processus vaginalis dynamics), and primary testicular production errors (intrinsic dysgenesis) [1,2]. In such heterogeneity, no single therapy will cure all.

In 2025, two pillars define management:

  • Surgical orchidolyse and orchidopexy (open or laparoscopic, depending on location) remains the gold standard to achieve and maintain scrotal position, with well-established techniques and high success rates when performed by experienced
  • Hormonal therapy (hCG, GnRH or LHRH analogs) is not supported as primary descent-inducing therapy in true undescended testes, but there is emerging and debated evidence that adjunctive low-dose, intermittent GnRH analog treatment following successful orchidopexy may promote germ-cell maturation and potentially improve later fertility in selected boys [1–5].

This review articulates the benefits and drawbacks of these approaches, aligns them with guidelines, and maps them to outcomes that matter for families—especially fertility and paternity—while weaving in pragmatic insights from clinical practice (e.g., diagnosis and timing) as presented in the symposium session.

Pathophysiologic frame: why treatment choice matters

Multifactorial origins

The pathogenesis of cryptorchidism involves:

  • Endocrine signaling (HPT axis, “mini-puberty,” androgens’ effects on downstream tissues),
  • Mechanical guidance (epididymal development, gubernacular swelling, patent processus vaginalis), and
  • Primary gonadal dysgenesis (intrinsic germ-cell deficits) [1,2].

Because etiologies differ, the response to hormones and the value of surgery alone differ across subgroups. Recognizing this, modern guidelines place primary emphasis on timely orchidopexy and selective use of hormones for fertility preservation rather than descent induction [1–3].

What endpoints should we value?

Beyond “the scrotal position of the testis,” relevant endpoints include:

  • Histology (presence of Ad spermatogonia; Nistal score) as a proxy for future spermatogenesis;
  • Serum markers (inhibin B, FSH/LH, testosterone) that reflect Sertoli/Leydig function;
  • Semen parameters in adulthood;
  • Paternity, acknowledging it is an imperfect, culturally and behaviorally confounded endpoint but ultimately family-important [1–3,6–9].

Primary hormonal therapy to induce testicular descent: benefits and drawbacks

Evidence of limited efficacy for descent

Multiple systematic reviews and meta-analyses—Cochrane and others—have shown modest and inconsistent descent rates with hCG or GnRH when used as primary therapy, with frequent re-ascent and no durable benefit compared with surgery [3–5]. Consequently, major guidelines advise against routine use of hormonal therapy to induce descent in true undescended testes [1–3].

  • The AUA guideline (2014, reiterated in later overviews) concludes that providers should not use hormonal therapy to induce testicular descent owing to low response rates and lack of sustained efficacy [2].
  • The EAU/ESPU guidance similarly does not recommend medical treatment to induce descent, but leaves room for post-surgical fertility-oriented regimens in selected boys [1].

Benefit: Rare cases (particularly canalicular testes close to the scrotum) may transiently descend with GnRH, possibly avoiding an operation in the short term.

Drawbacks: Low sustained success; risk of re-ascent; and with hCG, androgenic adverse effects (scrotal pigmentation, penile growth, behavioral changes), pain, and concerns about germ-cell apoptosis in some experimental and clinical reports [3–5,10,11].

Net: Do not use primary hormones to induce descent in true cryptorchidism. Proceed to timely orchidopexy.

Safety profile of hormones

  • hCG: Androgenic side-effects are common; some studies suggest increased germ-cell apoptosis and potential harm to future spermatogenesis, especially with higher/longer dosing [10,11].
  • GnRH/LHRH (e.g., buserelin): Nasal low-dose regimens are generally well tolerated, with mild local effects; systemic adverse events are uncommon at intermittent, low doses used post-orchidopexy in published series [4,5,9].

Surgical orchidolysis and orchidopexy: benefits and drawbacks

What orchidolysis and orchidopexy reliably delivers

  • Anatomic success: Experienced pediatric urologists achieve high, durable scrotal positioning, particularly when employing complete cremasteric dissection, division of the processus vaginalis high at the internal ring, and a tension-free dartos pouch placement (“subdartos”)—critical steps to prevent recurrence [1,2].
  • Testicular environment: Scrotal relocation represents a lower than the core body temperature, favoring germ-cell survival compared to retained abdominal/inguinal position.
  • Growth/Surveillance: Earlier surgery aligns with better testicular growth trajectories and enables palpation for tumor surveillance later in life [1–3].
  • Biopsy opportunity: In intra-operative contexts, biopsy permits risk stratification (Ad spermatogonia presence, Nistal score) to guide adjuvant decisions [6–9].

Timing matters

The consensus trend has shifted earlier: perform surgery by 12 months and no later than 18 months (corrected for prematurity), recognizing that many boys who are undescended at 6 months will not achieve spontaneous descent thereafter [1–3]. Earlier orchidopexy correlates with higher rates of favorable histology and better long-term function in population analyses and guideline syntheses [1–3].

Limits of surgery

  • Intrinsic dysgenesis: Some testes are histologically poor regardless of position; surgery alone cannot convert a Sertoli-only or severely depleted germ-cell compartment into normal spermatogenesis.
  • Ascending (acquired) testis: Even testes documented as scrotal in early childhood can ascend later, often with a patent processus vaginalis; vigilance and school-age examination programs remain important [12]. There are 2 peak moments for higher chance to develop ascending testis in the development of the child: 6-7 years and 11-12 years of It has been shown that fertility potential can be compromised in the ascending testis at this age, and this although the testis was previously documented in the scrotum.
  • Fertility not guaranteed: Orchidopexy improves the odds but is not synonymous with normal semen or paternity—especially in bilateral disease [6–9].

Post-orchidopexy GnRH/LHRH therapy aimed at fertility: benefits and drawbacks

Rationale: rescuing mini-puberty–linked germ-cell maturation

Ad (dark) spermatogonia emergence during mini-puberty is a key determinant of later sperm output. Histologic studies associate absence of Ad spermatogonia in cryptorchid testes with poor adult semen and subfertility. This has led to the hypothesis (spearheaded by Hadžiiselimović and collaborators) that low-dose, intermittent GnRH after the testis is in the scrotum may re-trigger or amplify HPT-axis signaling to promote germ-cell maturation (Ad transformation), benefiting future fertility [4,6–9].

What the data show

  • Histology: Several series report increases in germ-cell counts or Ad spermatogonia after nasal buserelin (e.g., 10 μg every other day for 6 months) in boys at high infertility risk on biopsy, compared with surgery alone [6–9]. Some cohorts documented durable histologic gains at follow-up biopsy approximately two years later [6–9].
  • Hormones: Improvements or favorable trends in inhibin B (Sertoli function) and LH/testosterone have been observed in long-term follow-ups of boys treated with adjunctive GnRH versus controls, though sample sizes are modest and selection biases possible [8,9].
  • Adult semen/paternity: Adult-age outcomes remain limited by loss to follow-up and cohort size. Available studies suggest possible semen quality advantages in treated boys, particularly those with bilateral disease and high-risk histology, but conclusive paternity benefits are not yet robustly demonstrated across independent centers [7–9].

Benefit: In selected high-risk boys (bilateral cryptorchidism, poor histology), post-orchidopexy low-dose GnRH may improve germ-cell maturation markers and hormonal milieu, plausibly translating into better semen in adulthood.

Drawbacks: The evidence base is not uniform; randomized, adequately powered, multi-center trials with adult endpoints are sparse. Access to buserelin or equivalent formulations varies by country; treatment necessitates months-long adherence. Families should be counseled that benefits are probable but not guaranteed.

Fertility and paternity after cryptorchidism: what should we tell families?

Unilateral vs bilateral

  • Unilateral cryptorchidism: Paternity rates approach the general population (≈90–94%) in many series when treated appropriately, although subtle semen abnormalities can occur [12].
  • Bilateral cryptorchidism: Paternity is reduced (≈60% range in classic cohorts), even with surgery; fertility counselling is essential .

These figures, cited in guideline summaries and classic cohorts, underline the heterogeneity of outcomes and the importance of early, expert care [1–3,].

Practical diagnosis and selection pitfalls (why some “failures” are preventable)

Although this paper focuses on treatment, outcomes are sensitive to accurate diagnosis and selection, themes repeatedly emphasized in our clinical program:

  • Differentiate retractile testes from true undescended; the cross-legged “frog” position and patience (2 minutes) help the cremasteric fibers relax, improving palpation accuracy. Over-diagnosis leads to unnecessary surgery; under-diagnosis delays needed care [1,2].
  • Avoid routine imaging (US/CT/MRI) before referral for palpable testes; imaging seldom changes management and may mislead. Ultrasound can aid in non-palpable or very obese infants but has modest sensitivity/specificity; diagnostic laparoscopy is the gold standard when the testis is truly non-palpable [2,13].
  • Recognize ascending (acquired) testis: School-age peaks in orchidopexy reflect acquired ascent; many of these boys have a patent processus vaginalis at surgery [12]. Vigilant pediatric screening programs matter.

Sound diagnosis ensures we apply the right therapy to the right child at the right time—the foundational benefit that underpins all downstream gains.

Putting it together: individualized, multifactorial care

A contemporary algorithm

  1. Confirm the phenotype
    • Palpable vs non-palpable; true undescended vs retractile; consider syndromic contexts (e.g., hypospadias, DSD). Avoid non-actionable imaging [2,13].
  2. Time surgery appropriately
    • Plan orchidopexy by 12 months (no later than 18 months), earlier if spontaneous descent seems unlikely after 6 months corrected age [1–3]. Use meticulous technique (complete cremasteric dissection, high ligation of processus vaginalis, careful spermatic vessel handling, tension-free subdartos placement).
  3. Consider biopsy when it will change management
    • Especially in bilateral disease and/or late presenters, biopsy (if local pathology expertise exists) can stratify infertility risk (Ad spermatogonia) and guide adjuvant GnRH discussions [6–9].
  4. Offer adjunctive low-dose, intermittent GnRH after successful orchidopexy selectively
    • Particularly in bilateral undescended testes with high-risk histology; counsel families about potential benefits (germ-cell maturation, hormonal markers) vs uncertainties (adult paternity) and practicalities (drug access, adherence) [4,6–9].
  5. Long-term follow-up
    • Growth, position, testicular consistency; adolescent counseling; adult fertility assessment when appropriate.

Where the field should go

  • Multi-center RCTs powered for adult outcomes (semen/paternity) to definitively test post-orchidopexy GnRH strategies;
  • Biomarker refinement (beyond biopsy): non-invasive surrogates of germ-cell health would democratize selection;
  • Mechanistic work on HPT-axis programming and epididymo-gubernacular mechanics to uncover new adjuncts (e.g., CGRP-pathway modulators).

Benefits and drawbacks—succinct comparative summary

Strategy

Key benefits

Key drawbacks / limits

Primary hormonal therapy (hCG, GnRH) to induce descent

Rare short-term descent inselected low canalicular testes

Low durable success, high re-ascent; hCG side-effects and possible germ-cell harm; not recommended by guidelines [1–5,10,11]

Orchidopexy (early, expert)

High durable scrotal position; improved environment; surveillance; enables biopsy-guided risk stratification

Cannot correct intrinsic dysgenesis; fertility not guaranteed, especially bilateral; requires anesthesia and surgical expertise [1–3,6–9]

Adjunctive low-dose, intermittent GnRH after successful orchidopexy

In selected high-risk boys, improves germ-cell markers (Ad spermatogonia), inhibin B trends; plausible semen benefit

Evidence heterogeneous; adult paternity benefit not conclusively proven; limited access to buserelin in some regions; months-long adherence [4,6–9,]

Conclusions

  • Surgery first: For true undescended testes, orchidopexy—performed early and expertly—remains the cornerstone with the most certain benefits.
  • No to primary hormones for descent purpose: Routine hormonal induction of descent is not recommended; benefits are small and transient; risks and re-ascent are real.
  • Yes, consider post-surgical GnRH selectively: After successful orchidopexy, low-dose, intermittent GnRH analog therapy( 6 months) may confer fertility-relevant advantages in biopsy-defined high-risk boys, particularly with bilateral disease. Families should be informed of potential gains and current uncertainties.
  • Measure what matters: Where possible, anchor decisions in histology (Ad-spermatogonia, Nistal score) and track inhibin B and long-term semen. Continue to pursue adult endpoints, including paternity.
  • Get the basics right: Accurate clinical diagnosis (no-touch patience, frog-leg positioning), avoidance of unnecessary imaging, and recognition of ascending testis will reduce overtreatment and undertreatment alike.

The overarching message is pragmatic: multifactorial condition, multifactorial care. We should keep our scalpel sharp, our endocrine lens focused, and our humility intact as we match the right patient to the right combination at the right time.

Declaration Section

  1. Ethics Approval and Consent to Participate Investigations were carried out in accordance 326 with the Declaration of Helsinki of 1975, revised in 2008.
  2. Consent for publication Not applicable
  3. Availability of data and supporting material Not applicable
  4. Competing interests Author/s declare that they have no competing interests
  5. Funding none

Acknowledgments

With appreciation to mentors and colleagues who shaped these perspectives, and to families whose long-term follow-up makes real-world outcome science possible.

References

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  2. Kolon TF, Herndon CD, Baker LA, Baskin LS, Baxter CG, Cheng EY et American Urological Assocation. Evaluation and treatment of cryptorchidism: AUA guideline. J Urol. 2014 Aug;192(2):337-45. doi: 10.1016/j.juro.2014.05.005.
  3. Ritzén EM, Bergh A, Bjerknes R, Christiansen P, Cortes D, Haugen SE, et Nordic consensus on treatment of undescended testes. Acta Paediatr. 2007;96:638-43. DOI: 10.1111/j.1651-2227.2006.00159.x
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  5. Cortes D, Thorup J, Petersen Efficacy of hormonal treatment for cryptorchidism: A review of the literature. Eur J Pediatr Surg. 1998;8(1):5-8.
  6. Hadziselimovic F, Zivkovic D, Bica DT, Emmons The importance of mini-puberty for fertility in cryptorchidism. J Urol. 2005 Oct;174(4 Pt 2):1536-9; discussion 1538-9. DOI: 10.1097/01.ju.0000181506.97839.b0
  7. Hadziselimović F, Herzog Treatment with a luteinizing hormone-releasing hormone analogue after successful orchiopexy markedly improves the chance of fertility later in life. J Urol. 1997 Sep;158(3 Pt 2):1193-5. doi: 10.1097/00005392-199709000-00130.
  8. Taran I, Elder Results of orchiopexy for the undescended testis. World J Urol. 2006 Aug;24(3):231-9. doi: 10.1007/s00345-006-0056-4.
  9. Ciongradi CI, Sârbu I, Iliescu Halițchi CO, Benchia D, Sârbu Fertility of Cryptorchid Testis-An Unsolved Mistery. Genes (Basel). 2021 Nov 26;12(12):1894. doi: 10.3390/genes12121894.
  10. Tseng CS, Huang KH, Chuang Does human chorionic gonadotropin therapy damage germ cells in cryptorchid testes? J Pediatr Surg. 2006;41:1203-7.
  11. Virtanen HE, Toppari Epidemiology and pathogenesis of cryptorchidism. Hum Reprod Update. 2008 Jan-Feb;14(1):49-58. doi: 10.1093/humupd/dmm027
  12. Lee PA, Coughlin MT, Bellinger Paternity and hormone levels after unilateral cryptorchidism: association with pretreatment testicular location. J Urol. 2000 Nov;164(5):1697-701. PMID: 11025752
  13. Shirazi M, Safavi S, Makarem A, Malekmakan Comparison Between Processus Vaginalis Sac Tightening Technique and the Conventional Technique in Orchiopexy Surgery Over 10 Years. Res Rep Urol. 2020 Mar 18;12:129-136. doi: 10.2147/RRU.S237824.

Guy Bogaert

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