**5. Conclusion**

*Lupus - Need to Know*

itself on ovarian function [90, 91] (**Figure 4**). It is possible that the underlying process is autoimmune oophoritis [92–94]. The clinical manifestations of these abnormalities are menstrual irregularity, amenorrhea, or premature ovarian failure. Menstrual irregularities are frequently observed in patients with SLE, and many of them are associated with the activity of the disease [95]. SLE itself induces dysfunction in the hypothalamic–pituitary-ovarian axis and elevates serum prolactin [35, 96, 97]. A study compared the levels of anti–müllerian hormone (AMH) as a marker of ovarian reserve between SLE patients and control subjects and found that SLE patients had significantly lower AMH levels than did the control subjects. No correlation was observed between disease activity and AMH levels [91]. Female SLE patients may have subfertility issues due to active disease, the use of immunosuppressive medications and delayed childbearing [98]. These findings show that SLE

SLE patients presenting with severe manifestations of the disease are treated with the alkylating agent cyclophosphamide [99, 100]. Cyclophosphamide is toxic to the ovaries [101–103]. SLE patients exposed to cyclophosphamide have a much higher risk of developing premature ovarian failure and infertility as compared to those receiving less toxic agents [91, 95, 104]. Cyclophosphamide leads to a decrease in reproductive life span and possibly premature ovarian failure. If the loss of ovarian function develops during or shortly after the completion of therapy, it is termed acute ovarian failure. For those who retain ovarian function after the completion of chemotherapy, a subset will go on to develop premature menopause before the age of 40 [105]. The clinical manifestations of ovarian damage in women at reproductive age vary from temporary irregular menses to amenorrhea, infertility, and premature ovarian failure depending on the magnitude of the damage. The probability of developing permanent ovarian failure depends on the following factors: patient's age and the type, dose, and duration of the treatment. If the patient is older and her ovarian reserve is low, they are less likely to retain or regain menstrual function than younger ones. Studies have documented that cyclophosphamide administration is the most significant risk factor for ovarian failure and that AMH is a sensitive and reliable marker of ovarian reserve and damage after exposure to cyclophosphamide in female patients with SLE [106–108]. In the case of cyclophosphamide administration in lupus patients fertility preservation may be attempted [108]. Currently, embryo or oocyte freezing are the established methods used for fertility preservation in patients receiving gonadotoxic treatment [109–111]. Other

itself has a negative influence on ovarian reserve and function.

*Factors adversely affecting ovarian function in systemic lupus erythematosus.*

**70**

**Figure 4.**

SLE is a systemic autoimmune disease which affects all organ systems and occurs frequently in female patients in the reproductive period. Estrogens appear to modulate the immune response, induce loss of self-tolerance, alter the Th1/Th2 balance in favor of the Th2 process, induce the survival of T and B lymphocytes and the production of autoantibodies. Estrogens appear to be involved in the pathogenesis of SLE. In SLE neuroendocrine system function is affected by the autoimmune process, the neuroendocrine system affecting in turn the disease process. Stress appears to affect disease expression in lupus patients. In SLE hypothyroidism occurs oftener than in the general population, hyperthyroidism occurs in the same rate as in the general population and Hashimoto's thyroiditis is present oftener than in a control population. Diabetes mellitus 1 occurs sometimes, diabetes mellitus 2 occurs less frequently than in the general population. Hyperparathyroidism has been observed in lupus patients. Addison's disease is extremely rare in lupus patients. Cushing's disease occurs infrequently in lupus patients. The ovarian function is affected in female SLE patients. Primary ovarian failure may occur due to autoimmune oophoritis. Cyclophosphamide in SLE is used and its use may be accompanied by the development of premature ovarian failure. The recognition of endocrine disease is important in SLE as symptoms may be similar to those of lupus, however management may be different. The recognition and treatment of an endocrine problem in SLE may guide treatment and lead to symptom amelioration and proper patient management.
