Several Factors Contribute to Impaired Fertility in Women, Men With CKD

Women and men with chronic kidney disease (CKD) are at risk for a number of fertility and sexual complications, which can stem from a range of sources, such as treatment, the nature of the disease, and depression related to CKD, according to a review.

The review, published in the Advances in Clinical and Experimental Medicines, compiled 85 studies to assess the full spectrum of fertility abnormalities in women and men with CKD before and after kidney transplantation, which can help support physicians in making adequate and informed treatment decisions regarding patients with renal diseases.

Fertility disorders are common among people with CKD and impact women and men with similar severity and in different ways. Interruptions to sexual life and procreation can lead to worsened quality of life and mental health issues in patients with CKD. Additionally, these interruptions are often overlooked or ignored by physicians.

In women, fertility disturbances can manifest as sexual function disorders, endocrine abnormalities that can lead to irregular menstrual cycles, impaired ovarian function, and reduced ovarian reserve. Fertility issues in men often presents as erectile dysfunction (ED), endocrine abnormalities, and testicular damage along with impaired spermatogenesis.

Women with CKD experience impaired fertility most commonly with stage 5 CKD, also known as end-stage renal disease. Women younger than 40 years old treated with hemodialysis therapy have a higher prevalence of primary ovarian insufficiency compared with the general population. They are also more like to experience menopause about 4.5 years earlier than women without kidney disease. Pregnancy in women on chronic dialysis therapy is rare, occurring about 40 times less frequently than the general female population.

Sexual function disorders occur in about 60% to 70% of women treated with hemodialysis. Sexual function disorders in women with CKD may be caused by decreased libido and hypoactive sexual desire disorder, depression and adverse effects of antidepressant medications, peripheral neuropathy, anemia, and cardiovascular disorders.

Endocrine abnormalities that cause irregular menstrual cycles can be caused by hyperprolactinemia, low estradiol concentration, or disturbed pulsatile secretion of gonadotropin-releasing hormone, luteinizing hormone (LH), follicle-stimulating hormone (FSH). Hyperprolactinemia occurs in 30% to 60% of women with CKD.

Damage from uremic toxins and a low amount of anti-Müllerian hormone (AMH) can lead to impaired ovarian function and reduced ovarian reserve, which is a term used to describe the quality and quantity of follicles that are present in the ovaries.

Not much is known about the prevalence and pathogenesis of fertility dysfunction in male patients with CKD. However, the prevalence of ED occurs in 70% to 80% of men with CKD, much higher than the general population.

Several factors can cause ED in men with CKD, including cardiovascular disorders, decreases in nitric oxide synthesis, autonomous dysfunction of the nervous system, depression and antidepressant medications, peripheral neuropathy, anemia, zinc deficiency, adverse effects of antihypertensive medications, obesity, and cigarette smoking.

Endocrine abnormalities in men may be caused by elevated LH and FSH concentrations and hyperprolactinemia. However, low levels of total testosterone and free testosterone can contribute as well.

Similarly to women, fertility may be impaired by low AMH concentrations. Other factors, such as Sertoli cell atrophy, testicular fibrosis, morphological extra-testicular disturbances, and decreased number and motility of sperm cells can cause testicular damage or impaired spermatogenesis. Men with spermatogenesis often have oligozoospermia, asthenozoospermia, decreased ejaculate volume, and abnormalities in the heads and tails of spermatozoa.

Kidney transplantations in women have shown to improve female fertility. However, fertility is often not stable. Pregnancy occurs 4 times more frequently in women who have undergone transplant surgery, which is still about 10 times less frequently compared to the general female population. Hormone stabilization, normal sexual function, and regular menstrual cycles often return following kidney transplantation as well.

In men, studies have shown that kidney transplantations can normalize levels for testosterone, LH, and FSH. Alas, transplant surgery can’t fully repair the morphological damages to the testes and will not normalize semen quality in comparison with men without CKD. Increases in spermatogonium, spermatozoon, and spermatocyte counts have been observed. No increases in Sertoli cell numbers or changes in serum AMH levels have been reported. Studies assessing whether kidney transplantation can improve ED have produced conflicting results.

Reference

Kuczera P, Więcek, Adamczak M, et al. Impaired fertility in women and men with chronic kidney disease. Adv Clin Exp Med. 2022;31(2):187-195. doi:10.17219/acem/141188