Is Hypogonadism Hereditary?

by Benjamin Bunting BA(Hons) PGCert

ben bunting BA(Hons) PgCert Sport & Exercise Nutriton  Written by Ben Bunting: BA(Hons), PGCert. Sport & Exercise Nutrition. L2 Strength & Conditioning Coach.

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Like a lot of health conditions, you may want to uderstand if hypogonadism is hereditary, so this article helps to address that question and we cover the following key points:

  • Causes of hypogonadism
  • Is hypogonadism hereditary?
  • Symptoms of hypogonadism
  • Conclusion 
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Hypogonadism refers to a condition in males in which the testes (male sex organs) function inadequately.

Their function is either absent or reduced and this results in low testosterone (T) levels[1]. Hypogonadism is diagnosed when a person has T-levels lower than 300 nanograms per deciliter (ng/dL)[2]. Having low testosterone is very challenging and can cause abnormal growth and functioning of the body.

Poor or absent functioning gonads can be precipitated by many reasons. Despite the more popular belief that hypogonadism develops in many elderly men, especially over the age of 65, the condition occurs in newborns too.

It can also be congenital and hereditary- terms that are often confused. Hereditary refers to the passing on of a trait in the lineage or through genes, while a congenital condition refers to a condition that is present since birth.

Congenital anomalies are not always but can be hereditary. Modern science has discovered that fact that hypogonadism, can be hereditary i.e., it can pass on from parents to the child[3].

Scientists have also been able to locate the causes of various hereditary hypogonadism cases. In this article, we will discuss some hereditary factors leading to or preceding hypogonadism.

Causes of Hypogonadism

To understand the hereditary link of abnormally low testosterone we first have to look at some of the main causes of this condition.

These causes can be divided into two groups, primary and secondary hypogonadism.

Primary hypogonadism refers to a condition in which the low levels of testosterone are attributed to the fault in the testes themselves, e.g., underdeveloped testes.

Contrastingly, secondary hypogonadism arises due to another underlying disease e.g., hypothyroidism. [4–6]

Primary Hypogonadism

Here are some diseases or conditions that are classified under primary male hypogonadism:

• Klinefelter syndrome – a male with two more X chromosomes and with one Y chromosome. Normally, boys have one X and one Y chromosome.
• Undescended Testes – testes in a fetus are mostly developed in a location
• Hemochromatosis – a condition in which there is iron overload. Excess iron is toxic to the testicles. [6–8]

Secondary Hypogonadism

Some of the conditions considered to be under the umbrella of secondary hypogonadism are:

Kallmann’s syndrome – abnormal development of the hypothalamus. Hypothalamus is an important part of the brain that regulates many hormones in our body including the production of testosterone. Dysfunctional hypothalamus can cause hypogonadism.
Pituitary disorders – pituitary gland functions similarly and in a close connection with the hypothalamus in regulating many of your body’s hormones. Loss of the pituitary gland or its functions may precipitate hypogonadism. [6–8]

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Is Hypogonadism Inherited?

According to the current literature hereditary hypogonadism could be classified into two categories. Idiopathic hypogonadism i.e., the exact behind it cannot be identified. Secondly, hereditary hypogonadism is due to other inheritable diseases.

Idiopathic hypogonadotropic hypogonadism (IHH)

IHH is a condition in which dysfunction is associated with the gonadotropin-releasing hormone (GnRH).

Low levels or absent GnRH around the second decade of life leave a person without sexual growth.

According to certain studies, there are genetic abnormalities, for example, inactivation of gene CDCD141, that lead to IHH and almost 50% of the cases were hereditary [9,10].

Hereditary Hemochromatosis (HH)

Hereditary hemochromatosis, as the name suggests, is an inherited disease that is characterized by iron overload.

The high levels of iron have deleterious (disturbing) effects on the gonadotropic axis. The gonadotropic axis refers to the GnRH release and its effect on the gonads.

HH often develops silently and causes low testosterone. Fortunately, due to advances in the pre-screening tools, the number of people affected is decreasing.[11,12]

Kallmann’s Syndrome (KS)

This condition is a subtype of hypogonadotropic hypogonadism characterized by the loss of GnRH hormone (leading to delayed or absent puberty) and the sense of smell.

Kallmann’s syndrome, in most cases, is inherited in an autosomal dominant (AD) pattern. AD is a pattern of inherited diseases, in which defect in only of the parent genes is enough to cause abnormalities.

Inheritance of KS, therefore, could be a reason for the inheritance of hypogonadism. [6,13–16]

Myotonic Dystrophy (DM 1)

DM1 is a multisystem disease affecting various normal body functions. It is characterized by muscular defects, testicular and tubular atrophy, cardiac anomalies, mental retardation, and cataracts [17,18].

Myotonic dystrophy is also inherited in an autosomal dominant (AD) pattern. Having an AD pattern shows that a person with myotonic dystrophy has a 50% chance to pass it on to each of their kids. [19]

Symptoms of Hypogonadism

is hypogonadism hereditary?

As mentioned above, testosterone is required for the development of various organs and their proper function.

The symptoms, therefore, vary according to the age of the individual being affected by the condition.

Testosterone and Fetal Development

Fetuses suffering from low testosterone most commonly have abnormal external sexual organs.

For instance, they may have:
• Female-looking external sex organs despite having male chromosomes (genetic material)
• Ambiguous sexual appearance
• Underdeveloped male sexual organs [6]

Puberty

A lot of people discover the disorder during puberty.

Hypogonadal males might have:
• Low muscle mass
• Sharp, feminine-like voice
• Absent or scanty facial hair
• Below average size of the penis
• Gynecomastia (enlarged breast tissue in men)6

Adults

Adults can experience a wide variety of symptoms associated with the hormonal ailment.

They may include:

These symptoms allude to the fact that hypogonadism is quite devastating at any age, especially congenital or hereditary hypogonadism.

How to Naturally Fix your Testosterone Levels 

Naturally, you can induce your testosterone production in several ways. Some common examples are:

  • Exercising regularly, especially weight training
  • Eating a balanced diet containing protein, omega-3 fatty acids, fibers
  • Enjoy adequate sleep
  • Reduce a stressful lifestyle
  • Spend more time doing what you like
  • Have a good sexual life
  • Use a natural supplement with clincially proven ingredients

Conclusion

Hypogonadism in males has various causes which can be hereditary and non-hereditary.

While several other inherited diseases can lead to hypogonadism, establishing the fact that having impaired gonads itself is hereditary needs more research.

The hereditary diseases associated with hypogonadism include hemochromatosis, idiopathic hypogonadotropic hypogonadism, Kallmann’s Syndrome, etc.

Therefore, it is not yet established that men with hypogonadism only are sure to pass it on to their offspring.

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References:

1. Prevalence, Diagnosis and Treatment of Hypogonadism in Primary Care Practice » Sexual Medicine » BUMC. Accessed January 15, 2022. https://www.bumc.bu.edu/sexualmedicine/publications/prevalence-diagnosis-and-treatment-of-hypogonadism-in-primary-care-practice/
2. What You Need to Know About Low Testosterone What You Need to Know About Low Testosterone | News | UW Health. Accessed January 15, 2022. https://www.uwhealth.org/news/what-you-need-to-know-about-low-t
3. Rejuve Health Clinics Low Testosterone: Could your genes be to blame? • Rejuve Health Clinics. Accessed January 15, 2022. https://www.rejuvehealthclinics.com/male/low-testosterone-genes-blame/
4. Donnelly P, White C. Testicular dysfunction in men with primary hypothyroidism; reversal of hypogonadotrophic hypogonadism with replacement thyroxine. Clinical endocrinology. 2000;52(2):197-201. doi:10.1046/J.1365-2265.2000.00918.X
5. Vaz de CR, Maria AJ, Ferreira F, Gomes V, Wessling A, Joao BM. Hypogonadotropic hypogonadism in a patient with long-term primary hypothyroidism. Endocrine Abstracts. 2017;49. doi:10.1530/ENDOABS.49.EP1055
6. Male hypogonadism - Symptoms and causes - Mayo Clinic. Accessed January 15, 2022. https://www.mayoclinic.org/diseases-conditions/male-hypogonadism/symptoms-causes/syc-20354881
7. Hypogonadism: MedlinePlus Medical Encyclopedia. Accessed January 16, 2022. https://medlineplus.gov/ency/article/001195.htm
8. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone Therapy in Men with Hypogonadism: An Endocrine Society. Journal of Clinical Endocrinology and Metabolism. 2018;103(5):1715-1744. doi:10.1210/jc.2018-00229
9. Turan I, Hutchins BI, Hacihamdioglu B, et al. CCDC141 Mutations in Idiopathic Hypogonadotropic Hypogonadism. The Journal of Clinical Endocrinology & Metabolism. 2017;102(6):1816-1825. doi:10.1210/JC.2016-3391
10. Topaloğlu AK. Update on the Genetics of Idiopathic Hypogonadotropic Hypogonadism. Journal of Clinical Research in Pediatric Endocrinology. 2017;9(Suppl 2):113. doi:10.4274/JCRPE.2017.S010
11. McDermott JH, Walsh CH. Hypogonadism in Hereditary Hemochromatosis. The Journal of Clinical Endocrinology & Metabolism. 2005;90(4):2451-2455. doi:10.1210/JC.2004-0980
12. el Osta R, Grandpre N, Monnin N, Hubert J, Koscinski I. Hypogonadotropic hypogonadism in men with hereditary hemochromatosis. Basic and Clinical Andrology. 2017;27(1). doi:10.1186/S12610-017-0057-8
13. Costa-Barbosa FA, Balasubramanian R, Keefe KW, et al. Prioritizing genetic testing in patients with kallmann syndrome using clinical phenotypes. Journal of Clinical Endocrinology and Metabolism. 2013;98(5). doi:10.1210/JC.2012-4116
14. Valdes-Socin H, Almanza MR, Fernández-Ladreda MT, Debray FG, Bours V, Beckers A. Reproduction, smell, and neurodevelopmental disorders: Genetic defects in different hypogonadotropic hypogonadal syndromes. Frontiers in Endocrinology. 2014;5(JUL). doi:10.3389/FENDO.2014.00109
15. Kim SH. Congenital hypogonadotropic hypogonadism and Kallmann syndrome: Past, present, and future. Endocrinology and Metabolism. 2015;30(4):456-466. doi:10.3803/ENM.2015.30.4.456
16. Kallmann syndrome: MedlinePlus Genetics. Accessed January 16, 2022. https://medlineplus.gov/genetics/condition/kallmann-syndrome/#inheritance
17. Sarkar PS, Paul S, Han J, Reddy S. Six5 is required for spermatogenic cell survival and spermiogenesis. Human molecular genetics. 2004;13(14):1421-1431. doi:10.1093/HMG/DDH161
18. Kim W bin, Jeong JY, Doo SW, et al. Myotonic Dystrophy Type 1 Presenting as Male Infertility. Korean Journal of Urology. 2012;53(2):134. doi:10.4111/KJU.2012.53.2.134
19. Myotonic dystrophy | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program. Accessed January 16, 2022. https://rarediseases.info.nih.gov/diseases/10419/myotonic-dystrophy