Does Growth Hormone Suppress the Gonadal Axis?
No, recombinant human growth hormone (rhGH) therapy does not suppress the gonadal axis or cause hypogonadism in humans. In fact, the evidence demonstrates that GH and the gonadotropin-releasing hormone (GnRH)-gonadotropin system are interconnected and mutually supportive rather than antagonistic.
Key Evidence from Guidelines and Research
The available clinical data consistently shows that rhGH therapy does not impair gonadal function:
In Adult Males with GH Deficiency
rhGH replacement does not suppress gonadotropins or testosterone production. A controlled study in GH-deficient adult males found no effect of GH treatment on basal testosterone levels, testicular response to hCG stimulation, or pituitary FSH/LH response to GnRH challenge 1. Another study in adult males with organic GH deficiency showed that while total testosterone decreased during rhGH treatment, this was due to decreased sex hormone-binding globulin (SHBG), and calculated free testosterone remained unchanged—meaning bioavailable testosterone was preserved 2.
In Pediatric Populations
Long-term follow-up of boys treated with rhGH shows normal gonadal development and function. A study of boys with non-GH-deficient short stature treated with rhGH demonstrated normal testicular volume, regular androgenization, and hormone levels within normal adult range after completion of pubertal development, with semen parameters within almost normal limits 3.
Mechanistic Understanding
The relationship between GH and the gonadal axis is actually synergistic rather than suppressive 4. GH and IGF-1 stimulate GnRH and kisspeptin neurons, support luteinizing hormone release, and regulate gonadal steroidogenesis. Conversely, sex steroids (particularly estradiol) potentiate GH secretion. This crosstalk is most prominent during puberty when the synergistic rise of sex steroids, GH, and IGF-1 creates an anabolic environment.
Important Clinical Considerations
Monitoring Requirements
According to the Endocrine Society guidelines, thyroid and adrenal function should be monitored during GH therapy 5, as GH replacement can lower free T4 levels and unmask central hypoadrenalism. However, the guidelines do not recommend routine monitoring for gonadal suppression because this is not an observed effect.
Subtle Hormonal Changes
While rhGH does not suppress the gonadal axis, it may cause subtle hormonal shifts: one study found slightly elevated estradiol levels and decreased prostate-specific antigen during GH treatment, though both remained within normal range 1. These represent minor anti-androgenic effects at the biochemical level without clinical hypogonadism.
Animal vs. Human Data
Be cautious interpreting animal studies. While prepubertal rhGH treatment in male rats showed earlier puberty onset and elevated testosterone 6, direct neuronal studies in mice showed rhGH does not directly affect GnRH neuronal activity 7. Human clinical data should take precedence over animal models.
Clinical Bottom Line
When evaluating a patient on rhGH therapy with concerns about gonadal function, look for:
- Actual clinical signs of hypogonadism (decreased libido, erectile dysfunction, loss of secondary sexual characteristics)
- Measure free testosterone rather than total testosterone, as SHBG changes can be misleading 2
- Consider other causes of hypogonadism rather than attributing it to GH therapy
- Remember that GH deficiency itself does not mask central hypogonadism 2, unlike its masking effect on hypothyroidism and hypoadrenalism
The concern about gonadal suppression from rhGH therapy is not supported by clinical evidence and should not be a barrier to appropriate GH replacement therapy.