This article examines the current evidence available on fertility in Wilson’s disease, which is a rare disease of copper metabolism that has pathological effects on many organ systems in the body.  

It is an autosomal recessive disorder that leads to an accumulation of copper in the brain, liver and other vital organs. Copper buildup can also affects the body’s endocrine systems. The incidence rate of Wilson’s disease in Ireland is 17.0 per million live births and it is indicated that one in 122 of the population is a gene carrier.¹

All sources with information on the topic of fertility in Wilson’s disease are included in this article regardless of their level of evidence. Literature searches included the SCOPUS, British Medical Journal and Medline databases. This review looked at information from a case study, review article of a large number of cases, some case series and a cohort study. The sources found did not contain enough information or have a large enough patient sample to come to definitive conclusions about fertility in Wilson’s disease, but as the prevalence of this disease is small this is to be expected to some extent. 

The lack of adequate information on the topic could lead to difficulty for both patients and healthcare workers and is clearly an area where more research is required, particularly in the area of fertility effects of the disease in males.

Case study: endocrine problems

The effect of Wilson’s disease on endocrine systems is highlighted in a case report of a woman who presented solely with endocrine disturbances. 

The patient presented with symptoms associated with excessive insulin and prolactin release. However, prolactin levels were repeatedly tested and found to be normal. An MRI scan preformed on the patient showed a hypoactive area of the pituitary gland that was found to have no hormonal function. 

An ultrasound on the woman showed features of polycystic ovary syndrome but no abnormalities in androgen levels were detected. The patient’s hormonal disturbances had led to menstrual abnormalities progressing to amenorrhoea. 

A diagnosis of Wilson’s disease was given after a liver biopsy was performed. After four months of treatment with zinc acetate the patient’s menstrual cycles returned to normal and galactorrhoea disappeared.²

This case study is important as it shows an association between Wilson’s disease and endocrine disturbances. The fact that the symptoms resolved with treatment is also important as this suggests although hormonal disturbances can occur and fertility may be affected in untreated women, there is hope that treatment can restore normal function and fertility.

Case series: abnormal ovarian function

One case series involved four women diagnosed with Wilson’s disease who reported abnormal ovarian function.  All patients had normal adrenal, thyroid, pituitary and hypothalamic function on testing. However, the women all had low levels of oestradiol, high total testosterone (T), normal free T, and mildly elevated androstenedione. 

The authors theorised that an interference of ovarian follicular aromatase activity possibly due to copper intoxication could be the cause of the ovulatory disturbances of Wilson’s disease. This case series highlights the effects Wilson’s disease can have on the fertility of female reproductive system, as functioning ovaries are required for normal fertility function. We are not told if any women in the case series had problems with conception or what treatment they were receiving, so it is difficult to draw conclusions from this study.³

Case report: amenorrhoea

Another report also notes amenorrhoea among 46 female patients, along with infertility and miscarriages. 

Hypogonadism, gynaecomastia and impotence were found among the 27 male patients. The study found that only untreated symptomatic women had trouble conceiving, four out of 31 such patients needed hormone therapy to achieve a pregnancy. 

The study found that female patients, who were asymptomatic, had mild symptoms or patients who were properly treated had no problems becoming pregnant. 

However, the report found that the rate of miscarriage was higher than normal in both groups, 26% of untreated and in 26.6% of treated women reported having a miscarriage. 

The study also examined fertility problems in male patients but as only one man complained of impotence no comparisons could be made between the study groups of symptomatic versus non-symptomatic and treated versus non-treated. 

This study seems to suggest that symptomatic untreated women are more likely to experience fertility problems than asymptomatic and treated women. It also showed a higher rate of miscarriages among both patient groups.⁴

Cohort studies: miscarriage and stillbirth

An article containing information from retrospective analysis of a cohort study of 59 pregnancies in 16 women with Wilson’s disease was also analysed. 

The report found that in the sample group there were 24 miscarriages and three stillbirths. The rate of miscarriage in the group was much higher than in the general population, 40.7% compared to 5% in the general population.

The study also noted recurring miscarriages were more common especially among the untreated group. This case series suggests that Wilson’s disease may be linked to an increased rate of miscarriages in women with the condition. 

The authors theorise that copper deposits in the uterus may interfere with implantation and also that multi-organ involvement resulting in liver disease, endocrine disorders, or anaemia may also contribute. 

The article fails to mention the treatment and symptom status of the patients.⁵

Summary of Wilson’s disease 

A review on movement disorders and pregnancy contained information from a number of earlier studies involving Wilson’s disease. One study showed elevated rates of miscarriages among women with Wilson’s disease and the other showed that drug treatments for the condition did not seem to have any adverse effects on fertility or pregnancy.⁶ The information available on fertility in Wilson’s disease seems to suggest that untreated symptomatic women may experience fertility problems including amenorrhoea. 

There is also an indication that Wilson’s disease may be linked to an increased rate of miscarriage. 

There is no information available on male fertility in relation to Wilson’s disease. The area of fertility in the condition is one that clearly needs to be studied in greater detail and at the moment there is a poor selection of information available for healthcare professionals.

References

1. Reilly M, Daly L, Hutchinson M. An epidemiological study of Wilson’s disease in the Republic of Ireland. J Neurol Neurosurg and Psychiatry 1993; 56(3): 298-300
2. Krysiak R, Handzlik-Orlik G, Okopien B. Endocrine symptoms as the initial manifestation of Wilson’s disease. Yale J Biol Med 2012; 85(2): 249-254. [Epub 2012] 
3. Kaushansky A, Frydman M, Kaufman H, Homburg R. Endocrine studies of the ovulatory disturbances in Wilson’s disease (hepatolenticular degeneration). Fertil Steril 1987; 47(2): 270-273
4. Tarnacka B, Rodo M, Cichy S, Czonkowska A. Procreation ability in Wilson’s disease. Acta Neurologica Scandinavica 2000; 101(6): 395-398
5. Sinha S, Taly AB, Prashanth LK et al. Successful pregnancies and abortions in symptomatic and asymptomatic Wilson’s disease. J Neurol Sci2004; 217(1): 37-40
6. Kranick S M, Mowry EM, Colcher A et al. Movement disorders and pregnancy: a review of the literature. Movement Disorders 2010; 25(6): 665-671