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New insights into sexual functioning and fertility in rheumatic diseases

https://doi.org/10.1016/j.berh.2004.01.002Get rights and content

Abstract

Sexuality is an often neglected area of quality of life in patients with rheumatic disease. Manifestations and symptoms of disease can impair sexual functioning, but this can be much improved by adequate intervention and counseling. Fertility is in general not reduced in rheumatic diseases, however, the time taken to achieve a pregnancy is often increased. An increased rate of pregnancy loss is observed in systemic lupus erythematosus and the antiphospholipid syndrome contributing to a reduced family size. Autoantibodies are present in most of the rheumatic diseases and can interfere with fertilization, implantation, embryonic development and placental function. Active disease disturbs the hypothalamic-pituitary-axis, giving rise to periods of gonadal dysfunction. Toxic effects of immunosuppressive drugs can induce transient or permanent gonadal failure in women and men.

Section snippets

Sexual functioning

Rheumatic disease can impair sexual functioning in several ways (Table 1). Physical problems, emotional problems and partnership difficulties arising from disease-related stress contribute to a less active and often less enjoyable sex life.1 Chronic pain, fatigue and low self-esteem can reduce an individual's sexual interest and thereby reduce the frequency of intercourse. The pleasure of intercourse can become diminished by pain of joint movement, or difficulty in finding positions that do not

Sex hormones and reduction of libido or fertility

Disturbances of sex hormone status can reduce libido and interfere with successful reproduction. In the following, some hormonal alterations occurring in rheumatic diseases and contributing to reproductive problems are presented. Several studies have investigated serum concentrations of hypophyseal, gonadal and adrenal hormones in women and men with rheumatic diseases and compared them to measurements in healthy, age-matched controls. No significant abnormalities in estrogen and progesterone

Fertility

Fertility is usually measured as the ability to conceive a child and fecundity as the time to achieving pregnancy. Rheumatic diseases can impair fertility and, more often, fecundity in several ways as indicated in Table 1. Complex interactions exist between active disease, autoimmunity, hormonal imbalance, sexual function and fertility.

Autoimmunity and reproductive failure

Autoimmune abnormalities have been associated with infertility.56 Antiphospholipid antibodies (aPLs) have received most attention since they were shown to be connected with pregnancy losses.57 aPLs react with negatively charged phospholipids and include the anticardiolipin antibody; lupus anticoagulant; antibodies to phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine; and antibodies to the cofactor β2 glycoprotein. Studies in mice showed that aPL not only induced pregnancy

Drugs and reproduction

Most antirheumatic drugs have no effect on the gonads. However, some drugs can cause reversible infertility like the nonsteroidal anti-inflammatory drugs (NSAID) in women and salazopyrin or methotrexate in men. Irreversible infertility is observed exclusively after treatment with alkylating agents like cyclophosphamide and chlorambucil (Table 4). Pulse cyclophosphamide combined with high doses of steroids has been shown to be the most effective treatment for lupus nephritis. This treatment is

Summary

Reversible or permanent infertility is multifactorial and includes the disease itself, drugs used to treat the disease, disease of the genital system, hypothalamic-pituitary-axis dysfunction, and autoimmunity. Sexual dysfunction is experienced equally by female and male patients and most often related to pain, fatigue and physical impairment. Disturbances of sexual functioning require open communication between patient and caregivers and adequate information given. Most disease-specific sexual

References (73)

  • S Yoshino et al.

    Sexual problems of women with rheumatoid arthritis

    Archives of Physical Medicine and Rehabilitation

    (1981)
  • F.W Kraimaat et al.

    Intrusiveness of rheumatoid arthritis on sexuality in male and female patients living with a spouse

    Arthritis Care Research

    (1996)
  • M Ostensen et al.

    Sex, reproduction, and gynecological disease in young adults with a history of juvenile chronic arthritis

    Journal of Rheumatology

    (2000)
  • F.N Skopouli et al.

    Obstetric and gynaecologic profile in patients with primary Sjögren's syndrome

    Annals of the Rheumatic Diseases

    (1994)
  • D Gordon et al.

    Androgenic status and sexual function in males with rheumatoid arthritis and ankylosing spondylitis

    Quarterly Journal of Medicine

    (1986)
  • S.T Vilarinho et al.

    Evaluation of the hypothalamic-pituary-gonadal axis in males with systemic lupus erythematosus

    Journal of Rheumatology

    (1998)
  • C.C Mok et al.

    Profile of sex hormones in male patients with systemic lupus erythematosus

    Lupus

    (2000)
  • S.M Sant et al.

    Cauda equina syndrome in ankylosing spondylitis: a case report and review of the literature

    Clinical Rheumatology

    (1995)
  • M Folomeev et al.

    Impotence in systemic lupus erythematosus

    Journal of Rheumatology

    (1990)
  • N.S Nowlin et al.

    Impotence in scleroderma

    Annals of Internal Medicine

    (1986)
  • M.A Aguirre et al.

    Gynecomastia and sexual impotence associated with methotrexate treatment

    Journal of Rheumatology

    (2002)
  • M Cutolo et al.

    Sex hormone status in women suffering from rheumatoid arthritis

    Journal of Rheumatology

    (1986)
  • F Flaisler et al.

    A study of ovarian function in rheumatoid arthritis

    Revue de Rhumatism

    (1995)
  • S.T Valtysdottir et al.

    Mental wellbeing and quality of sexual life in women with primary Sjögren's syndrome are related to circulating dehydroepiandrosterone sulphate

    Annals of the Rheumatic Diseases

    (2003)
  • D Gordon et al.

    Prolonged hypogonadism in male patients with rheumatoid arthritis during flares in disease activity

    British Journal of Rheumatology

    (1988)
  • B Tengstrand et al.

    Bioavailable testosterone in men with rheumatoid arthritis—high frequency of hypogonadism

    Rheumatology

    (2002)
  • R Tapia-Serrano et al.

    Testicular function in active ankylosing spondylitis. Therapeutic response to human chorionic gonadotrophin

    Journal of Rheumatology

    (1991)
  • D Mitra et al.

    Testosterone and testosterone free index in mild ankylosing spondylitis: relationship with bone mineral density and vertebral fractures

    Journal of Rheumatology

    (1999)
  • E.J Giltay et al.

    Serum testosterone levels are not elevated in patients with ankylosing spondylitis

    Journal of Rheumatology

    (1998)
  • F.J Jimenez Balderas et al.

    Ovarian function studies in active ankylosing spondylitis in women. Clinical response to estrogen treatment

    Journal of Rheumatology

    (1990)
  • Z Khalkhali-Ellis et al.

    Reduced levels of testosterone and dehydroepiandrosterone sulphate in the serum and synovial fluid of juvenile rheumatoid arthritis patients correlates with disease severity

    Clinical and experimental Rheumatology

    (1998)
  • J.F Skomsvoll et al.

    Number of births, interpregnancy interval, and subsequent pregnancy rate after a diagnosis of inflammatory rheumatic disease in Norwegian women

    Journal Rheumatology

    (2001)
  • A Kay et al.

    Subfertility before and after the development of rheumatoid arthritis in women

    Annals of the Rheumatic Diseases

    (1965)
  • Del Junco. Del Junco DJ: The relationship between rheumatoid arthritis and reproductive function (thesis). University...
  • J.L Nelson et al.

    Fecundity before disease onset in women with rheumatoid arthritis

    Arthritis & Rheumatism

    (1993)
  • T.D Spector et al.

    The pill, parity, and rheumatoid arthritis

    Arthritis & Rheumatism

    (1990)
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