Advances in Peritoneal Dialysis, Vol. 27, 2011

Gynecologic Issues in Chrysostomos A. Dimitriadis,1 Joanne M. Bargman2 Peritoneal Dialysis

This paper reviews the issues associated with the of significant loss in PD patients and may be reproductive system in the special population of responsible for iron deficiency and consequent “re- female patients with end-stage renal disease on sistance” to erythropoietin treatment. Menstrual flow peritoneal dialysis (PD). We summarize current has been reported to be heavier and to contain clots knowledge concerning cancer screening tests, elec- in dialysis patients. This heavy menstrual flow may tive and urgent gynecologic procedures, and the become a particular problem in women on warfarin issues of menstruation, contraception, pregnancy, therapy. In complicated cases, the need for suppres- and delivery in these patients. Finally, we present sive hormonal therapy to stop or reduce menstruation the potential effects of gynecologic problems on PD may be considered. In addition, tranexamic acid and the complications of PD that can present with (Cyklokapron: Pfizer, New York, NY, USA), an an- symptoms of the female genitalia. tifibrinolytic agent, can be used to reduce the amount of menstrual blood loss in selected cases (1). Key words Cyclic hemoperitoneum, cancer screening tests, preg- Cyclic hemoperitoneum nancy, gynecologic disease A clinical finding associated with menstrual is hemoperitoneum. Its presentation can vary from Introduction minor bloody contamination of the dialysate effluent, Women comprise a significant portion of the peri- giving it a light red discoloration, to the appearance toneal dialysis (PD) population. This paper reviews of gross blood in the effluent bag, which can be up- the special characteristics of common gynecologic setting (Figure 1). These signs can be accompanied issues in those women, including menstruation, by diffuse abdominal tenderness, attributed to a mild female-specific cancer screening tests (Pap smears chemical resulting from exposure of the and mammograms), contraception, pregnancy, and to blood. However, as frightening as this the impact of gynecologic disease on PD therapy. bloody effluent might be for the patient, the blood loss is usually not as severe as it looks. Discussion

Menstruation A considerable number of women of reproductive age with end-stage renal disease will continue to menstruate while on PD or will resume menses af- ter a period of uremia-associated amenorrhea. The implications of these menstrual cycles for fertility are unclear, but conception should be assumed to be a possibility. Menstrual bleeding can be a potential source

From: 1University Department of Nephrology, Aristotles University of Thessaloniki, Hippokration General Hospital, Thessaloniki, Greece, and 2Home Peritoneal Dialysis Unit and Department of Nephrology of the University of Toronto, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada. f i g u r e 1 Hemoperitoneum associated with menstrual bleeding. .102 Dimitriadis and Bargman

The causes of hemoperitoneum in PD patients t a b l e i “Benign” causes of hemoperitoneum can be divided into “benign” and “serious.” Among Menstruation the benign causes, those associated with the female Ovulation reproductive system account for most of the cases Bleeding or ruptured ovarian cysts (Table I). They include menstruation, ovulation, or Bleeding or ruptured renal cysts bleeding associated with the rupture of ovarian cysts. Trauma Serious causes can include bleeding associated with benign or malignant disease of intraperitoneal organs (such as , , and ) or even bleeding originating from the retroperitoneal space, complicating renal or (that is, a leaking abdominal aneurysm, renal cysts or tumors). Other serious causes of hemoperitoneum include bleeding as a complication of a medical procedure, varying from endoscopy and to erosion of an intra-abdominal vessel associated with placement of a PD catheter. Finally, hemoperitoneum can also be related to bleeding diatheses, including coagulopa- thies, and to severe uremia (2). A history of the timing of hemoperitoneum in relation to the menstrual cycle can be useful in associating it either with ovulation or with menstruation. Ovulation can sometimes lead to minimal intraperitoneal bleeding resulting from the rupture of an ovarian follicle during the ovulation process, typically in the middle of the menstrual cycle. Menstruation, on the other hand, can lead to hemoperitoneum by two possible mechanisms: f i g u r e 2 Laparoscopic view of lesions of bowel-wall endometrio- retrograde uterine bleeding and endometriosis of the sis. From Camara et al. (3), by permission of Oxford University peritoneal cavity. The first cause can be described as Press. retrograde menses, because uterine endometrial tissue can flux retrogradely into the fallopian tubes, which Because of the upsetting presentation of this open into the peritoneal cavity, allowing menstrual condition, every female patient of menstrual age blood to enter. In the case of peritoneal endometriosis, should be advised at the time of PD training about bleeding actually originates in the peritoneal cavity, the possibility of hemoperitoneum. This approach because of the presence of ectopic endometrial tissue is advisable regardless of whether the patient is (Figure 2) that sheds just like uterine endometrium at currently menstruating, because the reappearance of the time of menses (3), following the same hormonal menses after initiation of PD and resolution of uremia- signaling. Both causes typically result in a cyclic associated amenorrhea has been well described. hemoperitoneum that, in rare cases, can also be associated with the cyclic appearance of symptoms Cancer screening tests of mild peritonitis as a result of the presence of blood It is widely appreciated that routine Pap smears and in the peritoneal cavity. mammograms are recommended as screening tests Menses-related hemoperitoneum can potentially for cervix and breast cancer for women in the general be complicated by the development of intraperitoneal population. Dialysis patients show an increased inci- adhesions or catheter dysfunction because of obstruc- dence of virus-associated cancers. Large population tion by clots. It can be treated with flushes to rinse out studies have shown that these patients have higher the blood and with intraperitoneal heparin to prevent odds of cervical cancer, but not (for example) breast clot formation. cancer (4). Therefore, in the first instance, Pap smears Gynecologic Issues in Peritoneal Dialysis 103 are particularly indicated for dialysis patients who are Pregnancy at higher risk for cancer of the cervix. The literature contains no studies of pregnancy These screening tests do not pose any particular in PD with large numbers of patients; only very hazard to female PD patients; however, procedures small case series have been reported. Pregnancy that are more invasive—such as a cervical cone biop- on PD, although it occurs less often, appears to be sy—can be complicated by polymicrobial peritonitis more successful than in the setting of conventional with vaginal flora–associated bacteria. Experience thrice-weekly hemodialysis. However, in either at our centers leads us to recommend that any gyne- case, pregnancy has a better outcome if dialysis is cologic procedure more invasive than a Pap smear started after the patient has already conceived than (that is, endometrial or cervix cone biopsy) should when the patient becomes pregnant while already be performed with an empty peritoneal cavity and on dialysis (7). after the patient has received prophylactic antibiotics Several modality-specific characteristics have appropriate for vaginal flora. been postulated to confer an advantage for PD over The use of a cancer screening procedure in PD conventional hemodialysis. First, PD is associated patients should always be individualized for the pre- with more hours of dialysis, and duration of dialysis dicted survival of the patient. It has been suggested has been closely associated with outcome, beyond that the application of such protocols in older diabetic adjustment for the dose of small-solute clearance. dialysis patients would be expected to prolong their The prolonged and gentle dialysis provided by PD survival by only 5 – 15 days (5). That finding renders can avoid hypotensive episodes that compromise the test low-value in older patients with an overall placental blood flow. Another difference with he- poor life expectancy (6). modialysis that might contribute to a more favorable pregnancy outcome on PD is the absence of a need Contraception for anticoagulation. Pregnancy occurs less often in PD patients than in On the other hand, a potential problem with PD patients on hemodialysis (7), and this difference has during pregnancy is the enlarging uterus. The eventual been postulated to possibly be attributable either to result is a limitation on the peritoneal volume avail- less-adequate dialysis or, more plausibly, to mechanical able for dialysis. This consequence can be handled problems associated with PD technique. The PD fluid by changing the dialysis regimen, diminishing the might possibly wash away the eggs released by the dwell volume, and increasing the exchange frequency. ovaries during ovulation, because they have to traverse Another risk is impaired catheter drainage because of the peritoneal cavity to reach the Fallopian tubes. blockage by the growing uterus (10). Intrauterine devices for contraception are dis- Other potential maternal complications that couraged because there are anecdotal reports of should be expected are a worsening of hypertension peritonitis associated with their use in PD patients and an increase in the requirements for erythropoi- (8). This risk has to be balanced against the risks etin and iron. of an unwanted pregnancy and of the use of other Before delivery, the patient should drain the di- contraceptive methods. alysis fluid. Administration of antibiotic prophylaxis The potential risks of oral contraceptives include for procedure-associated peritonitis is prudent. Most exacerbation of underlying hypertension and a higher deliveries described in the literature have been by thrombotic risk, especially if the patient has ongoing Caesarean section. Even in that case, PD can usually heavy residual proteinuria. On the other hand, oral be resumed 2 days after delivery, with the use of small contraceptives have several potential benefits. Apart dialysate volumes and frequent exchanges. It should from reliable birth control, they also offer hormonal be noted that the infant of an end-stage renal disease supplementation that might be beneficial, because patient is born with a blood urea nitrogen level simi- many dialysis patients are sex-hormone-deficient (9). lar to that of its mother, which can result in osmotic Reacquiring a menstrual cycle might also be helpful diuresis and dehydration. by removing the unopposed estrogen exposure effect The risks for preterm labor and small-for- of amenorrhea and its carcinogenic potential for the gestational-age infants are common in pregnancies in uterine endometrium. hemodialysis or PD patients. Moreover, PD-associated 104 Dimitriadis and Bargman peritonitis can precipitate labor. The appearance of hemodialysis in the immediate postoperative period, and hemoperitoneum may be a helpful indication of an PD was successfully resumed after 2 – 3 weeks (13). obstetrical complication such as abruptio placentae or bleeding of the uterine wall. Summary Fetal complications include polyhydramnios. Menstruation resumes or continues in many women The reported incidence varies significantly, ranging on PD. It can be heavy and a source of significant from 18% to 100%, as do rates of intrauterine death. blood loss, and it is occasionally associated with he- Respiratory distress syndrome also seems to occur moperitoneum. Contraception should be considered with a high incidence that has been reported by for these patients after an individualized evaluation certain authors to vary from 14% to 80% in preterm and discussion of the risks and benefits of the various and small-for-gestational-age infants. However, contraceptive methods. Cervical and breast cancer overall infant survival has recently been reported to screening tests pose no particular problems in PD, be 76% (11). but would be indicated mainly in patients with a good overall prognosis. It is reported that PD patients can PD-specific problems associated with gynecologic successfully carry a pregnancy to live birth, but the disease complication rate is higher than that seen in the gen- A rare PD complication that has been reported in eral population. Finally, the presence of dialysate in female patients is catheter obstruction because of the pelvis has led to many reports of complications envelopment by fimbriae of the fallopian tube (12). involving the internal and external genitalia. Another well-described complication of the raised intra-abdominal pressure associated with PD is uter- Disclosures ine prolapse. This condition can often be managed The authors have no conflicts of interest to declare. conservatively with a vaginal pessary and a change of PD prescription—for example, use of nightly in- References termittent PD or low-volume day dwells to lower the 1 Marret H, Fauconnier A, Chabbert-Buffet N, et al. intra-abdominal pressure. Clinical practice guidelines on menorrhagia: manage- Leakage of peritoneal fluid through a patent ment of abnormal uterine bleeding before menopause. processus vaginalis has been associated with the Eur J Obstet Gynecol Reprod Biol 2010;152:133–7. appearance of labial edema. However, that compli- 2 Lew SQ. Hemoperitoneum: bloody peritoneal di- cation occurs less often than scrotal edema in male alysate in ESRD patients receiving peritoneal dialy- patients does, because men more often have a patent sis. Perit Dial Int 2007;27:226–33. processus vaginalis on account of the presence of the 3 Camara O, Herrmann J, Egbe A, et al. 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