The publisher's final edited version of this article is available at Cancer J See other articles in PMC that cite the published article. As survival rates for hematopoietic stem cell transplantation HSCT have grown in the past two decades with improved management of acute toxicities, 1 — 2 attention to long term complications has become more salient to clinicians, researchers, and survivors themselves.
Sexual dysfunction has been defined as one of the most common long term issues following HSCT. HSCT is a procedure designed primarily for hematologic malignancies such as leukemia and lymphoma, although some solid tumors and non-malignant diseases such as aplastic anemia are also treated with this aggressive treatment method.
Prior to the transplant, to prepare the body to receive stem cells, the conditioning regimens always include chemotherapy, usually supralethal doses of an alkylating agent such as cyclophosphamide or busulfan, and often including total body irradiation TBI at a dose of cGy or higher.
This process lowers immune defenses so that stem cells from either marrow or peripheral blood, donated from oneself autologous or from another person allogeneic can be infused. If the transplant is allogeneic, survivors are at risk for chronic graft versus host disease GVHD , where the donor immune cells identify the body as foreign and attack it. Chronic GVHD can manifest anywhere in the body and often involves the skin, liver, eyes, mouth, sinuses and gut.
Chronic GVHD is managed with the use of immunosuppressants that often include high dose corticosteroids along with a calcineurin inhibitor such as cyclosporine or other newer agents that suppress immune recovery and bring a host of potential additional complications.
This increasingly widely used methodology for treating hematologic malignancies seems to spare gonadal function along with other organ systems, but risks for chronic GVHD remain.
The population of HSCT survivors who receive high dose treatment is usually well under the age of 50, and most often relatively healthy until their diagnosis. Since treatment is so arduous and potentially toxic, major comorbidities are exclusions for eligibility for transplant.
Thus women are frequently premenopausal and many men and women report active sex lives until the start of cancer treatment. While some transplant recipients have had several cycles of treatment prior to HSCT, others may have had little exposure to previous chemotherapy effects.
The dramatic changes brought by treatment can make sexual adjustments more challenging than those of older adults already experiencing adaptations to aging-related physiological changes. This context begins to explain some of the deficits seen even many years after treatment in these HSCT survivors. Medical Factors Contributing to Sexual Dysfunction Numerous components of medical treatment impact sexual function, including chemotherapy, TBI, medications for chronic GVHD, and the other treatments for symptoms or side effects that are commonly used in cancer patients, such as anti-depressants.
Alkylating agents are particularly toxic to gonadal function and consequently nearly all HSCT recipients are infertile following treatment although infertility is not guaranteed, leaving a level of uncertainty unless confirmed with fertility testing.
TBI is also toxic to gonadal function and can contribute to genital tissue sensitivity, atrophy or scarring. These treatments impair the production of testosterone at least for the first year for males, and induce ovarian failure for most women. Treatments are known to permanently damage function of the hypothalamic-pituitary-gonadal axis.
Most females have primary ovarian failure with consequent low endogenous estrogen levels, and vaginal tissue atrophy is a risk. Chronic GVHD may also contribute to vaginal introital stenosis and mucosal changes that contribute to dyspareunia, vaginal irritation, and increased sensitivity of genital tissues. Chronic GVHD can also cause inflammation, rash and sensitivity in the skin of the penis.
Most males recover Leydig cell function by one year, returning testosterone levels to within normal range. The type and dose of chemotherapy are factors to consider when identifying potential effects of treatment. This treatment not only suppresses endogenous hypothalamic and adrenal hormones, but also has major impacts on physical features and body image, along with potential for emotional lability and depression. Over time it creates cushingoid features with weight and fat gain along with loss of muscle.
Major joint problems are not uncommon and include avascular necrosis that can require joint replacement. With all of these changes, it is not surprising that feelings of attractiveness and sexual responsiveness suffer. For many survivors who experience this treatment and its effects, sexual activity is put on hold for years and can consequently be difficult to re-initiate without intervention. In this circumstance, a combination of medical and behavioral treatments may be needed.
The work to date in this area has focused on women and evidence of chronic GVHD effects specific to male genital tissue or sexual functioning has been very limited. When addressing sexual dysfunction in research or clinical care, it is important to consider contributions from biological effects on psychosocial factors. For example, low levels of testosterone in both males and females and years of high dose corticosteroid treatments for chronic GVHD are associated with decreased sexual desire and depressed mood.
Depression and anti-depressant use, along with insomnia are known risk factors for sexual dysfunction in the general population and occur widely in transplant recipients. Thus a full medical exam is needed for HSCT survivors who report sexual dysfunction. Consequently, separation of these factors is somewhat artificial. Figure 1 contains a conceptual model of sexual dysfunction that includes physiological and psychological aspects.
Fatigue, depression, insomnia, body changes, even pain or other physical discomforts may have biologic roots, but they also have cognitive and emotional consequences that can actively contribute to inhibiting sexual activity or responsiveness. If one barely has the energy to maintain mandatory daily activities to promote health, it can be hard to imagine saving time and energy for sex.
For survivors of HSCT this is a common experience in the months after treatment. In addition, appearance changes in hair loss, muscle loss, skin rashes, skin sensitivity or dryness, scars and weight changes influence body image which in turn contributes to sexual self-consciousness. Another barrier to return to sexual activity is the expectation that responsiveness should return to as it was before diagnosis. These worries and lack of communicating concerns are often also reflected in reduced intimacy, since emotional intimacy and physical expressions of closeness for many couples are seen as precursors to intercourse.
Patterns set in the months after returning home can turn into habits that continue for many years.