Table 2.
Summary of studies on reproductive hormone levels in boys with cryptorchidism and men with a history of cryptorchidism in childhood*.
| First authors |
Study design Country of investigation Study subjects (n) |
Age at hormone measurements, hormonal tests | Comparisons | Hormone results |
|---|---|---|---|---|
| At birth | ||||
| Bay et al. (50) | Prospective study Finland and Denmark 3 groups of boys - transient cryptorchidism (cryptorchidism <3 months of age) - Persistent cryptorchidism (cryptorchidism persisted > 3 months of age) - Controls Finland - 21 transient cryptorchidism - 20 persistent cryptorchidism - 20 controls Denmark - 11 transient cryptorchidism - 1 persistent cryptorchidism - 26 controls |
At birth | Cryptorchid vs. non-cryptorchid boys | Cord blood INSL3 level in Finnish boys with cryptorchidism was significantly lower than in controls. (non-significant difference in Danish boys) |
| Fénichel et al. (157) | Prospective case-control study France 26 boys with transient cryptorchidism 26 boys with persistent cryptorchidism 128 controls |
At birth | Cryptorchid vs. non-cryptorchid boys | Cord blood INSL3 level in cryptorchid boys was significantly lower than in controls. LH, T, hCG, AMH, inhibin B, and SHBG levels: not different |
| Mini-puberty | ||||
| Gendrel et al. (158) | Longitudinal study France |
Every month from the age of 1 to 4 months | Cryptorchidism with spontaneous testicular descent vs. persistent cryptorchidism | Plasma FSH was not different between 2 groups. |
| 57 term cryptorchid boys - 35 unilateral cryptorchidism - 22 bilateral cryptorchidism Cryptorchid boys classified into two groups: -Spontaneous testicular descent -Persistent cryptorchidism > 6 months |
Plasma LH and T levels were significantly lower in persistently cryptorchid boys. | |||
| Baker et al. (159) | Case-control study United Kingdom Cases: 21 boys born preterm (mean gestational age of 30 weeks) - 11 boys with unilateral cryptorchidism - 10 boys with bilateral cryptorchidism Controls: 21 boys matched for gestational age, birthweight, duration of ventilation assistance and duration of phototherapy |
Mean age of blood sampling -2 days 5 days weekly until hospital discharge (mean age of 67 days) Only plasma T levels were measured. |
Cryptorchid vs. non-cryptorchid boys | At 2 days and after 6 weeks: Cryptorchid boys had significantly lower plasma T levels than controls. |
| De Muinck Keizer-Schrama et al. (160) | Longitudinal study The Netherlands Three groups of boys, aged <1 y: Cryptorchidism persisted > 1 y (n = 29) (untreated) Spontaneous descent within 1 y (n = 19) Controls (n = 160) |
At 3, 6, 12 months: Basal and peak LHRH-stimulated serum LH and FSH Basal T At 12 months: Basal and post-hCG stimulation: T, DHT, and T precursors |
Persistent vs. transient cryptorchidism vs. controls | Basal, peak LHRH-stimulated LH and FSH levels were not different between three groups, except basal serum LH in group 2 was higher than that of group 3. Basal and peak LHRH-stimulated serum LH and FSH levels had similar changes over time. Basal and post-hCG stimulated serum levels of DHT and T precursors were not different between three groups. |
| Hamza et al. (161) | Longitudinal study France and Egypt 84 boys with cryptorchidism (42 unilateral and 42 bilateral) No controls 1-year follow-up |
Blood hormone levels at the age of 2–5 days 3 months 6 months |
Unilateral vs. bilateral cryptorchidism | Blood FSH, LH, T levels of unilateral and bilateral cases were not different. |
| Cryptorchidism with spontaneous testicular descent vs. permanent cryptorchidism | Boys with spontaneous testicular descent showed peak levels of LH and T at 2–3 months of age. FSH levels did not show the peak. Boys with permanent cryptorchidism: very low FSH, LH and T levels during study |
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| Raivio et al. (162) | Cross-sectional study Finland Cryptorchid and non-cryptorchid boys (total n = 80) |
At 3 months | Testis located at scrotal or high scrotal position vs. higher position or non-palpable | Testicular location of all boys with detectable serum androgen bioactivity was at scrotal or high scrotal position (n = 26). All boys with testis located at suprascrotal, or inguinal position or testes were non-palpable (n = 16) had undetectable serum androgen bioactivity. Boys with testis located in scrotal or high scrotal position (n = 23) had significantly higher serum T levels than those with higher testicular location or testes were non-palpable (n = 11). |
| Barthold et al. (163) | Case-control study USA 20 boys with non-syndromic cryptorchidism (15 unilateral cryptorchidism) 26 non-cryptorchid boys |
Plasma levels: 2 months of age Urine samples: every month from the age of 7 days to 4 months |
Cryptorchid vs. non-cryptorchid boys | No difference between the groups in the hormone levels in plasma levels of FSH, LH, total T, FAI, inhibin-B, estradiol, and SHBG or urinary levels of FSH, LH, T, and estradiol. |
| Suomi et al. (49) | Prospective cohort study Finland and Denmark Finland - 88 cryptorchid boys - 300 non-cryptorchid boys Denmark - 34 cryptorchid boys - 399 non-cryptorchid boys |
At 3 months | Cryptorchid vs. non-cryptorchid boys |
Finnish boys• Cryptorchid boys had significantly higher FSH, LH levels, FSH/inhibin B ratio and lower inhibin B levels. • T levels of the two groups were not different. Danish boys• Cryptorchid boys had significantly higher FSH level than non-cryptorchid boys. Other hormones were similar between the two groups. |
| Bay et al. (50) | Prospective study Finland and Denmark Finnish boys - 28 transient cryptorchidism - 51 persistent cryptorchidism - 100 controls Danish boys - 26 transient cryptorchidism - 11 persistent cryptorchidism - 51 controls |
At 3 months | Cryptorchid vs. non-cryptorchid boys | Both countries: Serum INSL3, LH, T levels between cryptorchid cases and controls were not different. Serum LH/INSL3 was significantly higher in persistently cryptorchid boys than that of controls. Serum LH/T ratio was significantly higher in persistently cryptorchid boys than that of controls (only among Finnish boys). Serum levels of INSL3, LH, and T, and LH/INSL3 and LH/T ratios between transiently cryptorchid boys and persistently cryptorchid boys were not different. |
| Pierik et al. (164) | Case-control study The Netherlands 43 boys with cryptorchidism 113 controls |
At 1–6 months | Cryptorchid vs. controls | Serum FSH, inhibin B, and AMH levels: not different between the 2 groups. Cryptorchid cases had significantly lower T and NSBT levels. |
| Prepuberty | ||||
| Gendrel et al. (165) | Cross-sectional study France 154 boys who had history of - Unilateral cryptorchidism (n = 64) or - Bilateral cryptorchidism (n = 90) 46 controls |
1 month−15 y | LHRH test Cryptorchid boys vs. control levels |
Peak LH levels in boys with history of cryptorchidism were significantly lower than controls (from infancy to early pubertal stage). FSH levels of boys with history of cryptorchidism and controls: no difference |
| hCG stimulation test | Basal plasma T levels: no difference between cases and controls Peaked T levels: blunted in boys with a history of cryptorchidism from the age of 1 year until mid-puberty |
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| De Muinck Keizer-Schrama et al. (160) | Described above | |||
| Longui et al. (166) | Cross-sectional study Brazil Boys with a history of cryptorchidism, aged below 4 y (n = 11) Boys with a hypospadias (used as controls) (n = 8) |
mean age: 2.2 y | Boys with a history of cryptorchidism vs. controls | Basal LH and T concentrations were not different between the 2 groups Boys with a history of cryptorchidism had significantly lower basal inhibin and higher FSH levels than controls. After hCG plus human menopausal gonadotropin (hMG) treatment, the inhibin-to-FSH ratio was significantly lower in boys with a history of cryptorchidism. |
| Christiansen et al. (167) | Cross-sectional study Denmark 62 boys with untreated cryptorchidism (45 unilateral and 17 bilateral cryptorchidism) 156 healthy, prepubertal boys |
Median age 7.7 y, ranged from 4.1 to 13.6 y | Cryptorchid vs. non-cryptorchid boys | Basal inhibin B, T, FSH, and LH levels between cryptorchid cases and healthy controls: no difference |
| Unilateral vs. bilateral cryptorchidism | Basal levels of inhibin B, T, FSH, and LH between boys with unilateral and bilateral cryptorchidism: no difference | |||
| Hormone levels of cryptorchid boys after 3-week hCG injection (n = 18) | After hCG treatment in cryptorchid boys, T increased into the adult range and FSH and LH were suppressed. | |||
| Iwatsuki et al. (168) | Cross-sectional study Japan Four groups of boys: Surgical treatment for unilateral or bilateral cryptorchidism (n = 23) Hypospadias (n = 49) Cryptorchidism and hypospadias (n = 10) Hydrocele (n = 7) |
At age: <12.5 y 12.5 to 13.5 y > 13.5 y and by Tanner stages |
Compare four groups of boys | FSH levels in boys with both cryptorchidism and hypospadias was significantly higher than those of the other groups at ages 12.5–13.5 and >13.5 y, and during Tanner stages II and III. LH and T levels were not different among the groups. |
| Komarowska et al. (169) | Cross-sectional study Poland Boys with unilateral cryptorchidism (n = 105) Boys with inguinal hernia (controls) (n = 58) |
Age 1–4 y | Boys with unilateral cryptorchidism vs. non-cryptorchid boys | Serum AMH, INSL3, and inhibin B of the two groups were not different. |
| Hamdi et al. (170) | Cross-sectional study France Cases: boys operated for cryptorchidism (n = 27) controls (n = 27) Age range: 14–32 months |
Mean age Cases: boys operated for cryptorchidism: 26.6 months Control group: 24.4 months |
Cryptorchid vs. non-cryptorchid boys | Serum inhibin B, AMH and testosterone levels of the boys operated for cryptorchidism were significantly lower than that of non-cryptorchid boys. (T levels were detectable in 10 cases and 10 controls.) |
| Grinspon et al. (171) | Retrospective, cross-sectional study Argentina Cryptorchid group Untreated bilateral cryptorchidism (n = 186) Untreated unilateral cryptorchidism (n = 124) Apparently normal boys (controls) (n = 179) |
Median age 3 y (range 0.03–13.6 y) | Cryptorchid vs. non-cryptorchid boys | Median AMH standard deviation score (for age of normal boys) in the cryptorchid group was below 0. |
| Unilateral vs. bilateral cryptorchidism vs. controls in each age group - 1–5.9 months - 6 months−1.9 y - 2–8.9 y - ≥9 y |
Serum AMH level of boys with bilateral cryptorchidism was significantly lower than that of the unilateral cryptorchidism and control groups between the age of 6 months to 1.9 y and between 2 to 8.9 y. Serum FSH and LH levels were not different between the three groups at any ages. |
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| Puberty | ||||
| Gendrel et al. (165) | Described in the pre-pubertal section | |||
| Dickerman et al. (172) | Longitudinal study Israel 106 boys with cryptorchidism - unilateral (n = 77) - bilateral (n = 29) Follow-up at least two times per year from the age of 5–14 y (Mean age 11.6 y) |
Plasma FSH and LH levels before and after LHRH test Plasma T level before and after hCG stimulation test The hormone levels were compared with normal range. |
LHRH test: Unilateral vs. bilateral cryptorchidism vs. range for normal boys for chronological age at various pubertal stages according to data from previous studies | - Basal FSH level in boys with unilateral cryptorchidism during prepuberty and bilateral cryptorchidism at mid-puberty and full puberty: higher than normal reference range. - Basal LH in boys with bilateral cryptorchidism: higher than normal reference range. - Post LHRH test, FSH level in cryptorchid boys: higher than normal reference range. - Post LHRH test, LH level: higher than normal range in boys with unilateral cryptorchidism at prepuberty and at mid-puberty. |
| hCG stimulation test: unilateral vs. bilateral cryptorchidism vs. range for normal boys for chronological age at various pubertal stages | - At the start of puberty: Unilateral cryptorchidid boys: basal and post-hCG stimulated T levels were higher than normal reference range. - At mid-puberty: basal T level in bilateral cryptorchidism group, aged 14–16 y, was lower than normal reference range. - At the end of puberty: basal T level in unilateral group was lower than normal reference range. T level after hCG stimulation was lower than normal reference range in cryptorchid boys. |
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| Adulthood | ||||
| Lee and Coughlin (4) | Cohort study USA Men with a history of bilateral cryptorchidism (n = 8) Men with a history of unilateral cryptorchidism (n = 109) Control men (n = 53) |
Adult age | Unilateral vs. bilateral cryptorchidism vs. controls | Men with a history of bilateral cryptorchidism had significantly lower inhibin B, significantly higher FSH and LH levels than men with a history of unilateral cryptorchidism and control men. |
| Brazao et al. (173) | Retrospective case-control study The Netherlands Group1: subfertile men with orchiopexy in childhood (n = 64, including 32 unilateral and 32 bilateral cryptorchidism) Group 2: non-cryptorchid subfertile men (n = 128) Group 3: fertile men (n = 32) |
Median age: Group 1: 31 y Group 2: 33 y Group 3: 32 y |
Subfertile men with orchiopexy in childhood vs. non-cryptorchid subfertile men vs. fertile men | Inhibin B levels of men in group 1 were significantly lower than those of men in group 2 and 3 FSH and LH levels in group 1 were significantly higher than those of group 2 and 3 FAI: no difference |
| Andersson et al. (174) | Cross-sectional Denmark 357 infertile men, including 72 men with a history of cryptorchidism (median age: 33 y) 318 fertile men, including 42 men with a history of cryptorchidism (median age: 30 y) Self-reported data |
Adult age | Fertile vs. infertile men | Among both fertile and infertile men, history of cryptorchidism was associated with decreased serum inhibin B levels. Among infertile men, history of cryptorchidism was associated with higher LH level, lower T/LH ratio and lower estradiol level. |
| Rohayem et al. (175) | Retrospective case-control study Germany Men with a history of cryptorchidism with or without treatment (222 unilateral and 135 bilateral cryptorchidism) Men with no history of cryptorchidism and had normozoospermia and normal testicular size at adult age (n = 709) Age: 16–58 y |
Mean age: Previous unilateral cryptorchidism: 34 y Previous bilateral cryptorchidism: 33 y Control men: 35 y |
Men with vs. without a history of cryptorchidism | Mean FSH and LH levels: significantly higher in men with a history of cryptorchidism Mean total and free T levels: significantly lower in men with a history of cryptorchidism Estradiol: no difference |
| Men with history of unilateral vs. bilateral cryptorchidism | Men with a history of bilateral cryptorchidism: significantly higher mean FSH and LH levels Mean total and free T, estradiol levels: no difference |
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*
Some studies included subjects at different periods of life. The studies are described in the section, in which the main results are reported.
DHT, dihydrotestosterone; FAI, free androgen index; T, testosterone; y, year.