How Does Growth Hormone Therapy Affect Fertility?

HGH plays an important role in fertility which is often overlooked

Recombinant human growth hormone (rhGH) is used to treat children with growth hormone deficiency (GHD), not only to improve final adult height, but also to improve body composition and bone health and promote healthy sexual development during puberty. Its role in early development is well known, and it continues to play a role in sexual health into adulthood. This article will look at the effect of low, normal and high endogenous levels of GH on fertility, as well as the effect of GH therapy.

Hormones Required for Male and Female Fertility

When people think of male and female fertility, the first hormones that often spring to mind are testosterone and oestrogen, respectively. This is understandable, since these are the hormones that are commonly administered in cases of delayed puberty to promote the development of secondary sexual characteristics.1 Although these are important for development and fertility, several other hormones work together to ensure normal sexual functioning.

It is important to note that there is no hormone that is specific to one sex. Instead, different levels of each sex hormone are found in both males and females. It is also worth noting that even though they are referred to as sex hormones, they are involved in functions that extend beyond sexual function. We will begin by looking at the hormones most commonly associated with sexual development and fertility and the roles they play in each sex.

FSH and LH

In men, FSH stimulates Sertoli cells in the testes, which support the production of sperm cells. LH stimulates Leydig cells in the testes, which produce the hormones testosterone and dihydrotestosterone, which are important for spermatogenesis.2,3

In women, these hormones are responsible for the growth of follicles in the ovaries and the release of eggs. LH also promotes the synthesis of androgens, which are necessary for follicle development.4,5

Testosterone and DHT

In men, these hormones both promote the growth of hair, muscles, the penis and testes during puberty. High levels of testosterone signal the pituitary to reduce FSH and LH production to regulate hormone levels and sperm production. This feedback mechanism is why abnormally elevated testosterone levels can reduce sperm production, reducing fertility.6 Despite being important for sperm production, healthy sperm can still be produced if testosterone levels are low.7

In women, testosterone also promotes hair and muscle growth, but to a lesser extent than in males. Androgens can also regulate follicular development and are a precursor to oestrogens.8

Oestrogen

In men, testosterone can be converted into oestrogen. Although testosterone is typically associated with increased sex drive, oestrogen also contributes to this, including enhancing the ability to maintain an erection. Just as we have seen with testosterone, the greatest benefit is received when hormones are kept within strict ranges. High levels of oestrogen are not desirable in men, as too much of this hormone can lead to gynecomastia, erectile dysfunction, infertility and low libido.9,10

In women, oestrogen is important for sexual development during puberty and is also responsible for regulating the menstrual cycle, the growth of the lining of the uterus and egg maturation.11

Prolactin

In men, prolactin acts on the testes and vas deferens and can suppress sperm production when levels are high. It acts on Leydig cells to regulate testosterone levels and sperm production.12

In women, this same hormone promotes breast tissue growth and milk production during and after pregnancy. Since men also have a small amount of breast tissue, high prolactin levels can also cause gynecomastia and lactation in men.13

TSH

When levels of TSH are either too high or too low, this can negatively impact fertility. In men, sperm production and quality are reduced. Libido is also decreased and erectile dysfunction may be experienced.14

In women, ovulation can become dysregulated and the chances of miscarriage increase when this hormone is not within normal ranges.15

This very basic overview gives us some idea of the role of well-known hormones in sexual development and function, so where does GH come into sexual health?

Growth Hormone and Its Involvement in Reproduction

Growth hormone is often overlooked regarding its role in reproduction, even though it is essential to the development of the reproductive system during puberty. In adulthood, it continues to be an important hormone for fertility.

It can affect the activity of other hormones by:

  • Enhancing the effects of FSH and LH16
  • Increasing the secretion of testosterone and oestradiol17
  • Mimicking the effects of prolactin18
  • Regulating thyroid hormones19

In the female reproductive system, GH regulates folliculogenesis, oocyte maturation and helps to maintain pregnancy while in its early stages. It:

  • Stimulates the expression of FSH and LH, increasing sensitivity to gonadotropins and the production of oestradiol.
  • Increases the receptiveness of the uterus to implantation
  • Promotes the growth and maintenance of the endometrium
  • Enhances progesterone synthesis
  • Regulates the development of the placenta.

GH expression leads to an increase in IGF-1, which also mediates many of these actions.20

In males, GH is required not only for sexual development during puberty, but also for:

  • Testosterone synthesis
  • Supporting spermatogenesis
  • The functioning of accessory sex organs such as the prostate gland and seminal vesicles.21

The importance of GH for fertility becomes even clearer when we look at examples of where GH levels are below normal levels.

The Effect of GHD on Fertility

GHD can be caused by congenital factors, such as genetic mutations or defects in brain structure. It can also be acquired in childhood or adulthood due to tumours, cancer treatments, traumatic brain injuries, infections or autoimmune diseases that lead to damage to the pituitary. There are also many cases where the cause of GHD is not known.

Because of the prominent role of GH during puberty and for normal sexual function, a deficiency in GH can lead to reduced fertility. We can see evidence of this in clinical studies where GH therapy is used in an attempt to improve fertility and pregnancy outcomes.

How GH Therapy Affects Fertility in GHD Patients

In women with GHD, rhGH can restore ovulation and improve fertilisation rate. One study that looked at IGF-1 levels during GHRT treatment found that women with higher IGF-1 levels had improved pregnancy rates and were less likely to suffer a miscarriage.22

In boys with GHD who were treated with rhGH, testicular volume increased significantly compared with the growth of untreated children of the same age. Given that testicular volume can indicate higher fertility, this would suggest that GH treatment is of benefit to the fertility of boys with GHD who are beginning puberty.23 In men with congenital GHD, GH therapy was found to work with exogenous gonadotropins to markedly improve spermatogenesis.24

How GH Therapy Affects Fertility in Non-GHD Patients

Research has found that GH therapy in those without GHD can be of benefit in some cases. GH may enhance the responsiveness to gonadotropins by upregulating the expression of gonadotropin receptors.25 GH appears to be of greatest benefit to women with diminished ovarian reserve,26 while those with normal ovarian response do not experience any significant benefit.27,28

In men with idiopathic oligozoospermia, GH treatment did not offer any improvement in sperm count after 5 months of treatment,29 but another study looking at the effect of GH on men with normogonadotropic idiopathic oligoasthenospermia found that semen volume, sperm count and motility increased in all patients after 6 months of treatment.30 This suggests that, under certain circumstances, there may be some benefit to GH treatment for those with non-GHD-related infertility, but the conditions under which it will offer greatest benefit have yet to be clearly defined.

How Supraphysiological GH Affects Fertility

We have seen how GHD leads to impaired fertility and how, in some cases of infertility not caused by GHD, GH therapy can improve sexual health. We will now look at the effects of pathologically and pharmacologically elevated GH levels on fertility.

In cases of endogenous acromegaly, the disrupted pulsatile secretion of gonadotropin-releasing hormone leads to hypogonadotropic hypogonadism in up to half of patients, which lowers LH, FSH and testosterone levels.31

Pharmacologically induced acromegaly can lead to abnormally high spikes in IGF-1 levels, which suppresses the secretion of gonadotropins. In men, this causes testosterone production and sperm quality to decrease.32,33

In women, elevated GH can cause the menstrual cycle to become disrupted and increase the chances of developing gestational diabetes and gravid hypertension.34

These examples show us that there is an optimal range that GH levels should fall within and deviating from this can have a negative impact on sexual health.

Conclusion

GH therapy is a useful tool in promoting normal pubertal development and improving the fertility of those with GHD and certain non-GHD-related infertility. It is still not fully understood which non-GHD populations will benefit most from GH therapy. Where GH levels are chronically raised above normal physiological levels, we can observe a negative impact on fertility, emphasising the importance of maintaining normal GH levels.

References

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