Common Gynecologic Issues in Patients Post-Kidney Transplantation

Women who undergo kidney transplantation face a broad spectrum of gynecologic concerns that span reproductive, peri‐menopausal, and postmenopausal stages of life. While many conditions mirror those seen in the general population, their presentation, evaluation, and management are shaped by the interplay of transplant‐related anatomy, immunosuppression, and altered hormonal regulation unique to KTR. Careful screening for malignancy, judicious use of contraceptives, early recognition of AUB, and proactive management of menopausal symptoms are critical to safeguarding both graft function and overall health. Evidence to guide care in this population remains limited, underscoring the need for collaborative research and multidisciplinary approaches. Ultimately, optimizing women's health for KTR requires balancing transplant outcomes with gynecologic outcomes.

As the frequency of kidney transplants increases and posttransplant survival outcomes improve, there is a growing patient population requiring comprehensive longitudinal healthcare. Restoration of renal function after transplant often leads to improved reproductive health, yet persistent hormonal alterations and chronic immunosuppression distinguish kidney transplant recipients (KTR) from the general population. End stage renal disease (ESRD) commonly disrupts menstrual function, with many premenopausal women on dialysis having irregular or absent menstrual cycles [ 1 , 2 ]. Impaired kidney function causes uremia and hyperprolactinemia, leading to disruption of luteinizing hormone and gonadotropin releasing hormone (GnRH) secretion.[ 3 ] Chronic inflammation and metabolic disturbances associated with chronic kidney disease (CKD) further impair GnRH secretion and downstream ovarian function. While kidney transplant does restore menstrual function for the majority of amenorrheic patients, hormonal abnormalities like increased estrogen and decreased progesterone often continue.[ 2 , 4 ] Persistent CKD‐related gonadal dysfunction contribute to anovulation, abnormal uterine bleeding, and premature menopause. Patients’ estrogen is therefore often unopposed, increasing their risk of endometrial hyperplasia and neoplasm [ 3 ]. Additionally, the immunosuppressive therapy required to prevent rejection complicates cancer screening, management of common gynecologic conditions, and surgical decision‐making. Thus, multidisciplinary care integrating transplant, nephrology, endocrinology, and gynecology is essential. This narrative review highlights common gynecologic issues encountered in KTR across their lifespan, emphasizing diagnostic considerations, therapeutic options, and areas where clinical practice must diverge from general population guidelines. Literature search strategy included review of PubMed, Google Scholar, and Scopus for dates January 2000 through October 2025 using combinations of keywords such as kidney transplant, renal transplant, solid organ transplant (SOT) combined with gynecologic topics such as contraception, menstruation, menopause, hormone therapy, cancer screening, and pelvic floor dysfunction. Articles were selected based on relevance to gynecologic care in KTR, with priority given to clinical guidelines, meta‐analyses, systematic review articles, and research studies with larger sample sizes and more recent publication. We present recommendations according to the available literature and existing guidelines, with acknowledgement of the strength and quality of evidence. Given the narrative nature of this review, a formal evidence‐grading system was not systematically applied. Overall, due to sparse or conflicting data, many recommendations are based on low‐level evidence and expert opinions. We limited the scope of this review to gynecologic concerns given the complexity of obstetric care in KTR. A separate article is necessary for adequate coverage of pregnancy and delivery in this population. KTR are at increased risk for certain gynecologic cancers and therefore require unique screening considerations (Table  1 ).[ 5 , 6 , 7 , 8 ] Major guidelines include those from the American Society of Transplantation (AST), Kidney Disease Improving Global Outcomes (KDIGO), United States Preventative Services Task Force (USPSTF), American College of Obstetricians and Gynecologists (ACOG), and American Society for Colposcopy and Cervical Pathology. Gynecologic cancers and their screening guidelines in KTR compared to the general population.[ 5 , 6 , 7 , 9 , 10 , 11 ]. Average risk = women without Lynch Syndrome, BRCA, or other genetic mutations predisposing to this type of gynecologic cancer. Many recommendations in KTR are based on observational data, with few randomized controlled trials specific to this population. Screening guidelines also vary internationally; providers should refer to their national guidelines alongside international recommendations and individual patient risk assessment when determining appropriate screening strategies. Overall, screenings in female KTR are recommended for common malignancies, including breast and cervical cancers.[ 5 , 6 , 7 , 8 ] While specific cervical cancer guidelines exist for KTR, most other screening recommendations mirror those for the general population. Non‐gynecologic cancer screening is beyond the scope of this review but is outlined by organizations such as KDIGO and USPSTF [ 7 ]. There are no specific screenings for uterine (including endometrial) or ovarian cancers in KTR. Current data from the most comprehensive meta‐analyses suggests no significant increase in risk for either cancer compared to the general population; however, data remain limited and conflicting.[ 9 , 10 ] Breast cancer incidence in KTR is similar to the general population, and screening recommendations are the same: women aged 40 to 74 years old should undergo mammogram every 1 to 2 years [ 6 , 11 , 12 ]. Cervical, vulvar, and vaginal cancers in KTR are more common, develop more rapidly, and may be more aggressive in immunosuppressed patients due to impaired immune clearance of oncogenic strains of human papillomavirus (HPV), leading to persistent infection and malignant potential.[ 7 ] Cervical cancer screening in KTR is generally recommended annually with pelvic examination and pap smear starting at age 21, with HPV testing added after age 30.[ 13 ] Annual exams also enable inspection for anal, vaginal, and vulvar cancers. [ 7 ] Unlike recommendations for the general population, no upper age limit has been established for cervical cancer screening in KTR.[ 6 ] The 3‐dose multivalent HPV vaccine provides protection against cervical, vaginal, and vulvar cancers and is recommended before renal transplant for individuals age 9 to 45. [ 6 , 14 ] If not given pretransplant, vaccination afterwards is recommended; however, immunogenicity is reduced.[ 14 ] In addition to cancer prevention, HPV vaccination decreases the risk of HPV‐associated cutaneous and anogenital warts, which are more prevalent and often more numerous in KTR due to prolonged immunosuppression.[ 15 ]

The authors declare no conflicts of interest.

As the general population of patients eligible for transplantation ages, menopause and perimenopause will be relevant to the care of more KTR. Perimenopause is the transitional period preceding menopause and typically begins 5 years before the last menstrual period. During this time, declining follicular activity results in hormonal changes that cause irregular menstrual cycles and menopausal symptoms, including cognitive, psychologic, vasomotor, and genitourinary changes.[ 66 ] Menopause is defined as the permanent cessation of menstrual bleeding due to the loss of ovarian follicular activity and is diagnosed clinically after 12 months of amenorrhea.[ 66 ] After this point, a woman is postmenopausal. The average age of menopause in the general population is 51 years, while the average age of menopause in KTR is 45.5 years.[ 67 ] This discrepancy is likely due to persistent CKD‐related HPG‐axis dysregulation and immunosuppressive medications in KTR. When a woman has cessation of ovarian function between ages 40 and 45, this is defined as early menopause. Primary ovarian insufficiency refers to loss of ovarian function before age 40.[ 66 ] Early menopause in the general population is associated with more‐severe menopausal symptoms and increased risk for fracture, cardiovascular disease, diabetes, dementia, depression, and overall increased mortality.[ 66 ] Because early menopause is more common in KTR, increased screening for these comorbidities is needed in this population.[ 1 , 67 ] Hormone replacement therapy in menopause (mHRT) is indicated for alleviation of menopausal symptoms.[ 68 ] Food and Drug Administration (FDA)‐approved indications include the treatment of moderate to severe vasomotor and genitourinary symptoms, prevention of osteoporosis in postmenopausal women, and mitigation of adverse outcomes seen in early menopause or primary ovarian insufficiency.[ 69 ] mHRT risks differ depending on the type, dose, duration of use, route of administration, and timing of initiation.[ 69 ] In KTR, local (i.e., transvaginal) estrogens can be administered as creams, tablets, or rings.[ 70 ] Vaginal estrogens have minimal systemic absorption and are therefore preferred for long‐term management of KTR with genitourinary symptoms.[ 68 ] Systemic mHRT generally involves oral or transdermal estrogens with the addition of oral progestins or LNG‐IUD. Side effects include nausea, weight gain, headaches, and vaginal bleeding. Risks include venous thromboembolism, gallbladder disease, and breast cancer.[ 69 ] KTR often have elevated baseline cardiovascular risk (e.g., CKD, hypertension, diabetes, metabolic effects of immunosuppressive therapy), complicating use. [ 24 ] Transdermal estrogen may be theoretically preferable over oral administration because it bypasses first‐pass metabolism, resulting in lower venous thromboembolic risk; however, data specific to KTR are limited.[ 69 , 71 , 72 ] Cardiovascular effects of mHRT also depend on timing of initiation, with diminished risk if started before 60 years of age or within the first 10 years of menopause.[ 69 ] Extended duration of use and advancing age increase risk, and therefore treatment duration is recommended to be the minimum amount of time needed to alleviate symptoms.[ 69 ] However, in early menopause without contraindications, mHRT is recommended until the average age of menopause.[ 70 ] Contraindications for systemic mHRT include AUB, liver disease, prior estrogen‐sensitive cancer, cardiovascular disease, stroke, and thromboembolic risk.[ 69 ] Few studies have investigated the safety and efficacy of mHRT in KTR. One study of oral progestin with transdermal estradiol in KTR showed symptom relief without increased risk of endometrial or breast cancer; however, KTR experienced a higher rate of liver dysfunction requiring discontinuation of therapy.[ 71 ] Therefore, careful clinical monitoring of kidney and liver function is recommended in KTR using mHRT. Overall, mHRT use in KTR requires individualized risk assessment, shared‐decision‐making, and consideration of alternative options. FDA‐approved mHRT includes bioidentical and non‐bioidentical hormones.  Both forms are available in various routes of administration, each of which has unique side‐effect profiles.[ 73 ]  Compounded hormone formulations are prepared in compounding pharmacies and have not undergone the FDA‐approval process for production, standardization of dosing, and safety. [ 69 , 73 ] There are additional routes of administration with popular compounded hormones including pellets and troches, however, concern exists over lack of standardized dosing and absorption. Therefore, FDA‐approved hormone options are always preferred for initial mHRT prescribing.[ 73 ] Vasomotor symptoms, including hot flashes and night sweats, begin in perimenopause and last a mean duration of 7 to 9 years.[ 70 ] These symptoms can significantly impact mood, sleep, productivity, and relationships.[ 74 ] While non‐pharmacologic options such as cognitive behavioral therapy, hypnosis, weight loss, and lifestyle modifications exist; pharmacologic options are more frequently used.[ 70 , 75 ] mHRT is considered the most effective treatment and is indicated for moderate to severe vasomotor symptoms in the general population without contraindications.[ 76 ] Limited data specifically in KTR suggest that using oral progestins with transdermal estradiol effectively relieves vasomotor symptoms with high patient satisfaction.[ 71 , 72 ] Again, many KTR may have contraindications to mHRT, requiring shared decision‐making and monitoring of kidney and liver function.[ 71 ] Nonhormonal FDA‐approved medications for the general population include paroxetine, a selective serotonin reuptake inhibitor (SSRI), and neurokinin (NK) receptor antagonists (fezolinetant, elinzannetant), both of which significantly reduce vasomotor symptoms in randomized trials.[ 70 , 77 ] It should be noted that these medications do not have any effect on other menopausal symptoms, nor do they aid in osteoporosis prevention.[ 77 ] Data on using SSRIs for vasomotor symptoms in KTR are limited; however, SSRIs are regularly used in KTR for psychiatric disease. Altered pharmacokinetics and interactions with immunosuppressants require low starting doses and close monitoring if initiated for vasomotor relief.[ 78 ] Fezolinetant, a NK‐3 receptor antagonist, and elinzanetant, a dual NK‐1 and NK‐3 receptor antagonist, are novel agents that reduce vasomotor symptoms by targeting hyperactivity of hypothalamic neurons involved in temperature regulation.[ 77 ] Common adverse effects include headache, gastrointestinal disturbances, and hepatic transaminase elevations that may require closer monitoring of hepatic function. Contraindications include hepatic impairment and severe renal impairment/ESRD.[ 77 , 79 ] Given variable renal function in KTR and potential interactions with immunosuppresants, caution is warranted and consultation with a transplant pharmacist is recommended.[ 80 ] Other medications are well‐studied and commonly used off‐label for relief of vasomotor symptoms, including other SSRIs and serotonin norepinephrine reuptake inhibitors (SNRIs), gabapentin, and oxybutynin.[ 70 , 76 ] While no studies investigate these medications for safety or efficacy for vasomotor symptoms in KTR, SSRI and SNRIs are commonly used in KTR for psychiatric treatment without adverse effects.[ 78 ] Gabapentin is frequently prescribed for neuropathic pain in KTR and requires renal dose adjustments and avoidance of opioids or benzodiazepines.[ 78 , 81 ] Oxybutynin for vasomotor symptoms has not been studied in KTR; however, improper dosage increases risk for urinary retention and should be used with caution in patients with renal or bladder impairment.[ 82 ] While over‐the‐counter supplements are readily available, they have been found to be no more effective than placebo.[ 70 ] Furthermore, these supplements have not been studied for any indications in KTR and have the potential for irregular dosages, hepatotoxicity, or harmful drug interactions.[ 76 ] Recent evidence suggests stellate ganglion block, where anesthetic is injected around the anterior cervical spine, may relieve vasomotor symptoms.[ 70 ] Although not specifically studied in KTR for this indication, nerve blocks in KTR have been safely performed without affecting graft function.[ 83 ] The usual precautions for infection mitigation in immunosuppressed patients should be observed. Genitourinary syndrome of menopause (GSM) encompasses genital, sexual, and urinary signs and symptoms associated with changes to the labia majora/minora, clitoris, vestibule/introitus, vagina, urethra, and bladder resulting from decreased estrogen.[ 84 ] Symptoms include dryness and irritation, dyspareunia, and urinary complaints such as dysuria, urgency, and recurrent UTI.[ 85 ] KTR are particularly at risk for UTI due to functional, anatomic, and immunologic issues relating to kidney disease, transplant surgery, and immunosuppressive medications.[ 74 ] GSM generally worsens with increasing duration of estrogen deficiency (i.e., time post menopause).[ 84 ] Exam findings include pale, dry, and thin vulvar tissue with loss of labial fullness. The vaginal mucosa will likewise be pale, with increased dryness and decreased rugae. First‐line treatment is local vaginal estrogen therapy.[ 85 ] Vaginal estrogen has minimal systemic absorption at standard doses and can therefore be used safely to prevent UTI and alleviate symptoms for the majority of KTR.[ 68 ] Notably, systemic mHRT does not prevent UTI in GSM and is not effective for comprehensive treatment of GSM.[ 68 ] Other treatment options include localized testosterone and DHEA.[ 86 ] Osteoporosis in menopause is driven by estrogen deficiency, which leads to decreased bone mass, deterioration of bone microarchitecture, and subsequent increased fracture risk.[ 87 ] mHRT is indicated for primary prevention of osteoporosis and may be particularly beneficial in KTR, who are at increased risk due to early menopause, ESRD‐related osteomalacia, and chronic immunosuppression.[ 88 ] However, as discussed above, mHRT comes with multiple risks, particularly in the KTR population. Decisions regarding treatment should include shared decision‐making with exploration of risks and alternative options. Bisphosphonates are effective for treating pre‐existing osteoporosis and improving bone density in KTR. KDIGO guidelines recommend bisphosphonates for the first 12 months after kidney transplant. However, no data are availible to support bisphosphonate use in KTR after the first year posttransplant.[ 89 ] Despite this lack, many centers perform annual DEXA screening and use bisphosphonates for osteoporosis management in KTR (regardless of menopausal status).[ 90 ] Other management strategies include vitamin D supplementation, calcitriol/alfacalcidol, denosumab, calcitonin, and teriparatide.[ 89 , 91 , 92 , 93 ] Overall, limited, low‐ to moderate‐certainty evidence exists regarding treatment of bone disease in KTR.[ 91 ] Therefore, individualized treatment approaches that account for patient‐specific factors such as renal function, safety profiles, and fracture risk are essential. Providers should also use serum studies, including abnormal levels of calcium, phosphate, parathyroid hormone, alkaline phosphatases, and 25‐hydroxyvitamin D, to guide management.[ 89 ] Similar to reproductive‐age women, AUB in perimenopause has multiple etiologies (Figure  1 ). Workup and treatment should be tailored based on history and physical. A special consideration in peri‐menopausal women is anovulatory cycles due to declining ovarian reserve. Patients may present with changes in cycle length, menses volume, or spotting; often with accompanying menopausal symptoms.[ 30 , 94 ] Evaluation should include endometrial sampling given the risk for hyperplasia and carcinoma from unopposed estrogen in anovulatory cycles.[ 94 ] Treatment in perimenopausal KTR mirrors that of reproductive‐age women and includes progesterone‐based options (e.g., IUD) and surgical options like endometrial ablation or hysterectomy.[ 28 , 29 , 30 , 34 , 94 ] Postmenopausal bleeding is defined as vaginal bleeding occurring more than 1 year after cessation of menses.[ 95 ] This is always considered abnormal and necessitates further evaluation. Etiologies include endometrial atrophy, endometrial polyps, and endometrial hyperplasia or carcinoma. In addition to the history and physical described previously for AUB, ACOG recommends TVUS or endometrial sampling for evaluation.[ 95 ] With the ultrasound‐based strategy, TVUS is used to determine endometrial thickness, and sampling is indicated if the endometrium exceeds 4 mm. Persistent bleeding despite a negative endometrial biopsy warrants hysteroscopy with dilation and curettage.[ 94 ] Treatment depends on underlying pathology: Bleeding associated with friable, atrophic endometrium is benign and can be managed with reassurance.[ 96 ] Bleeding due to polyp can be treated with polypectomy.[ 48 ] Endometrial hyperplasia without atypia can be managed with progestins.[ 28 ] Hysterectomy is indicated for patients with hyperplasia with atypia and for patients without atypia who fail medical therapy.[ 42 ] Cases of endometrial carcinoma should be referred to gynecologic‐oncology.[ 30 ] Non‐endometrial sources, including mHRT and ovarian or vaginal malignancy, should be considered if evaluation is negative.[ 28 ] UTI is the most common infectious complication in KTR and a major cause of morbidity and mortality.[ 97 ] Most UTIs occur within the first 3 months posttransplant, but risk persists long term, particularly in postmenopausal women with GSM.[ 74 ] Immunosuppression, altered urologic anatomy, and organs from deceased donors increase the risk.[ 98 ] Gram negative bacteria are the most common uro‐pathogens, with rising rates of multi‐drug‐resistant organisms.[ 74 , 99 ] Asymptomatic bacteriuria is frequent; however, routine screening and treatment are not recommended, as they provide no clear benefit and may promote antimicrobial resistance.[ 97 , 98 , 99 ] Symptomatic UTI classically presents with dysuria, frequency/urgency, and suprapubic pain. Allograft or costo‐vertebral tenderness may indicate upper tract involvement, as the native kidneys also remain susceptible to infection. Fever, malaise, or sepsis syndrome without localized urinary tract symptoms are also possible.[ 98 ] Due to immunosuppresion, all symptomatic UTIs in KTR are classified as complicated UTIs.[ 99 ] Symptomatic UTIs require prompt diagnosis and antimicrobial therapy. Urine culture should be collected and empiric antibiotics initiated based on local resistance patterns. Based on culture results and susceptibility, the appropriate antimicrobial can be chosen.[ 98 ] Prevention strategies include minimizing indwelling catheters and stents and optimizing glycemic control. Routine Pneumocystis prophylaxis with TMP‐SMX in posttransplant patients may prevent some UTIs.[ 97 , 98 , 99 ] Pelvic organ prolapse (POP) is characterized by the descent of pelvic organs into or beyond the vaginal canal due to weakening of muscles, fascia, and ligaments. Women may be asymptomatic or experience pelvic pressure, urinary or fecal symptoms, and/or sexual dysfunction.[ 100 ] POP can increase post‐void residuals, increasing the risk for UTI and reflux nephropathy.[ 101 ] Severe prolapse may lead to urinary tract obstruction, hydronephrosis, and unrecoverable renal dysfunction. [ 102 ] Prompt diagnosis and management are therefore important to prevent graft injury. Diagnosis is aided by history, pelvic exam, and standardized tools such as the Pelvic Organ Prolapse Quantification staging and Baden‐Walker system.[ 100 ] Attention should be paid to symptoms of bladder outlet obstruction.[ 102 ] Exam should assess the external genitalia and vaginal mucosa for atrophy, irritation, or ulceration. A split‐speculum technique with Valsalva can investigate anterior, apical, and posterior prolapse.[ 100 ] Post‐void residual measurement and urodynamic studies help assess urinary dysfunction.[ 100 ] Few studies examine POP in KTR, and no specific management guidelines exist. If graft function is stable and the patient is asymptomatic, observation with close follow‐up is recommended.[ 101 , 102 ] Pelvic floor physical therapy is indicated for symptomatic women. Pessaries, first‐line in the general population, are not contraindicated in KTR; however, infection risk of indwelling hardware in immunocompromised patients is a concern.[ 103 ] KTR using pessaries therefore require education on pessary care and close follow‐up.[ 104 ] Surgery may be indicated if conservative management fails. Case reports suggest pelvic reconstructive surgeries are feasible in KTR.[ 40 , 101 , 105 ] A vaginal approach is often chosen, though abdominal approach may be considered for patients at high risk of recurrence.[ 106 ] Perioperative considerations include locations of the transplanted kidney and ureter and management of immunosuppressive medications. While impaired inflammatory response in immunosuppressed patients may theoretically affect incorporation of synthetic mesh graft implants, mesh itself has not been associated with increased infection risk in KTR.[ 101 ] Overall, surgical interventions in KTR have improved POP symptoms without complications.[ 40 , 101 , 105 ]

Pregnancy soon after transplant increases maternal and fetal risks, making contraceptive counseling essential.[ 16 ] Prior to transplant, patients with childbearing potential must secure durable birth control methods. AST recommends deferring pregnancy for at least 1 year after SOT to allow graft stabilization and surgical recovery, based on moderate‐quality observational evidence.[ 17 ] Afterward, immunosuppression should be optimized for pregnancy. For example, mycophenolate mofetil is teratogenic and should be discontinued at least 6 weeks before conception and replaced with safer alternatives (Table  2 ). [ 7 , 16 , 18 , 19 , 20 ] Common immunosuppressive medications in KTR [ 7 , 16 , 18 , 19 , 20 ]. Pregnancy after transplant carries increased risks for hypertensive diseases, gestational diabetes, preterm birth, and caesarean delivery.[ 16 , 21 ] While data on graft loss are limited, delaying pregnancy until stable graft function is reached appears to lessen risks.[ 16 ] With appropriate counseling and stable immunosuppression, KTR may attempt pregnancy with support from their transplant and obstetric teams. A detailed discussion of pregnancy management in KTR is beyond the scope of this gynecology review, however, consultation with maternal‐fetal medicine specialists is important to minimize risks in planned posttransplant pregnancies. Contraception is therefore critical for ensuring graft health and preventing complications. The Center for Disease Control and Prevention (CDC) U.S. Medical Eligibility Criteria for Contraceptive Use provide guidance for contraceptive use in SOT recipients.[ 22 ] Combined hormonal contraceptives (CHC), defined as estrogen‐containing contraceptives, are acceptable in patients with uncomplicated graft function. Options include oral pills, transdermal patches, and vaginal rings. CHC are generally contraindicated in patients with complicated graft anatomy or function due to risks such as hypertension and thrombosis (Table  3 ).[ 16 ] Contraception in KTR using the CDC classification system [ 16 ]. Complicated graft condition = defined per the CDC as acute or chronic rejection or graft failure. CDC classes: 1 = no restrictions, 2 = benefits outweigh risks, 3 = risks may outweigh benefits, 4 = unacceptable risks. In the general population, CHC are not recommended for women with cardiovascular disease or cardiovascular risk factors such as diabetes and obesity, which are highly co‐morbid among patients with kidney disease and transplantation.[ 23 ] Furthermore, the development of cardiovascular disease posttransplant can be fatal, as cardiovascular disease is the leading cause of death in KTR with functioning allografts.[ 24 ] Limited data suggest CHC are effective in KTR without increased thrombosis or graft dysfunction.[ 23 ] However, one study found that 43% of oral CHC users and 30% of transdermal CHC users required antihypertensive medication adjustment during an 18‐month study period.[ 25 ] Given these risks and the availability of alternatives, CHC are preferred for patients with stable kidney function, well‐controlled blood pressure, and no other contraindications. Progestin‐based contraceptives include progestin pills and subdermal implants, injectable depot medroxyprogesterone acetate (DMPA), and levonorgestrel intrauterine devices (LNG‐IUD). Progestin‐only pills do not increase thrombosis or hypertension risk; however, they require strict adherence to maintain efficacy and limit breakthrough bleeding.[ 22 ] Implants have favorable safety profiles but lack KTR‐specific data and may cause irregular bleeding.[ 16 ] Although data are limited in KTR, DMPA is associated with thrombosis and reversible bone density loss in the general population.[ 22 ] Since baseline osteomalacia is prevalent in KTR due to kidney disease, steroid use, and earlier menopause, bone density should be considered prior to initiation.[ 23 ] Current observational evidence indicates that LNG‐IUD are effective and safe in transplant recipients.[ 23 ] Early theoretical concerns about reduced efficacy and increased risk of pelvic infection in immunosuppressed patients have not been seen.[ 23 ] Copper IUDs are also effective in KTR but are associated with heavier menstrual bleeding. Because anemia is common in ESRD and often persists posttransplant, copper IUDs may be less ideal for KTR perioperatively.[ 16 ] When a KTR of reproductive age presents with AUB, the potential etiologies are similar to those in the general population. Limited evidence indicates that AUB occurs at increased rates in KTR compared to the general population.[ 26 ] The PALM‐COEIN algorithm is helpful in classifying these etiologies as structural (PALM—polyp, adenomyosis, leiomyoma, malignancy/hyperplasia) and non‐structural (COEIN—coagulopathy, ovulatory dysfunction, endometrial, iatrogenic, not otherwise classified) (Figure  1 ).[ 27 ] The following recommendations are largely extrapolated from general population guidelines and expert consensus, as transplant‐specific data are limited. Etiologies of abnormal uterine bleeding using the PALM‐COEIN algorithm [ 27 ]. Created in BioRender. Graham, M. (2026) https://BioRender.com/dzd3ov0 . Evaluation follows the PALM‐COEIN framework and includes history, physical, laboratory tests, and imaging. History should include menstrual history (regularity, frequency, duration, volume) and relevant medical history including medications. Physical exam should include speculum and bimanual exam to localize pathology (uterus vs. vulvar, vaginal, cervical, or rectal).[ 28 ] Laboratory workup includes pregnancy tests, complete blood count, ferritin, coagulation panels, thyroid and liver function tests, updated cervical cancer screening, and endometrial sampling.[ 29 , 30 ] Transvaginal ultrasound (TVUS) is the optimal imaging modality for suspected structural pathology. Follow‐up imaging may be warranted, including hysteroscopy and saline‐infusion sonohysterography for intracavitary lesions.[ 30 ] Small studies indicate that hysteroscopic procedures are safe in KTR and can be conducted in‐office.[ 31 ] In premenopausal women less than forty five years old without risk factors for unopposed estrogen, endometrial sampling is not routinely required for AUB.[ 30 ] However, ESRD is associated with increased endometrial cancer risk due to increased estrogen in the setting of hypothalamic‐pituitary‐gonadal (HPG) axis immaturity.[ 3 ] Immunosuppression posttransplant further increases cancer risk.[ 6 ] Without clear screening guidelines, careful review of symptoms and patient education on abnormal bleeding are essential in KTR. Medical therapy with contraceptive agents, including CHC and progestins, is first‐line treatment for AUB and can be implemented during evaluation. [ 16 ] As discussed above, CHC use requires caution and is limited to select KTR without contraindications.[ 32 ] Standard medical therapies in the general population, such as nonsteroidal anti‐inflammatory drugs, gonadotropin‐releasing hormone agonists, and tranexamic acid, are unsafe or insufficiently studied in KTR and should generally be avoided.[ 33 ] If surgical treatment for AUB is warranted, considerations include complex anatomy and infection risk. Limited case reports and series demonstrate that gynecologic surgeries are feasible and safe in KTR. Hysteroscopic polypectomy/myomectomy and first‐ and second‐generation endometrial ablation have been successfully performed in KTR without graft dysfunction, infectious complications, or need for immunosuppressive modification.[ 31 ] A retrospective study of 62 KTR reported successful hysteroscopic endometrial ablation, with 87% of patients reporting decreased bleeding and 100% of patients without complications.[ 34 ] Fertility‐preserving options include polypectomy and myomectomy; endometrial ablation is appropriate for those not desiring future fertility. Importantly, endometrial ablation does not prevent pregnancy, requiring concurrent contraception. Uterine artery embolization (UAE) is another option for control of AUB in the general population who do not desire future fertility. A handful of case reports detail UAE being successfully performed in KTR.[ 35 ] However, UAE carries multiple risks to the graft, including contrast exposure and complex vascular anatomy. Strategies such as judicious use of contrast and radial artery access may mitigate some risks.[ 36 , 37 ] Given the lack of literature and multiple risks, a careful risk‐benefit discussion can guide treatment decisions. Hysterectomy is a definitive solution to AUB in patients who do not desire future fertility. Multiple case reports and small series have demonstrated safety and efficacy in KTR. Minimally invasive approaches are favored due to fewer complications and faster recovery, though open surgery may be needed for large uteri or adhesions.[ 38 , 39 , 40 , 41 , 42 , 43 ] In both, preoperative imaging is essential to define pelvic anatomy, including location of the transplanted kidney and its ureter as well as vasculature anastomoses. Intraoperative cystoscopy has been shown to detect ureteral injuries during hysterectomy with a sensitivity of 80%–90%.[ 44 ] While retrograde ureteral injection and prophylactic stent placement have been considered for the reduction of ureteral injury, these interventions have not consistently decreased the rate of ureteral tract injury and may increase the rate of urinary tract infection. [ 36 , 45 , 46 , 47 ] Perioperative co‐management of immunosuppression regimens and infection prevention is also vital.[ 40 , 43 ] Endometrial polyps typically present with intermenstrual bleeding. The incidence of polyps increases with age and occurs at similar rates in KTR and the general population.[ 48 ] Polyps can be diagnosed on transvaginal ultrasonography, hysteroscopy, or endometrial sampling. Because there is an increased risk for malignancy within a polyp, polyps should be removed via polypectomy. Removal has been shown to reduce AUB in 75% to 100% of patients with endometrial polyps.[ 30 ] Adenomyosis is defined as endometrial tissue present in the myometrium and may cause heavy, painful, and/or prolonged menstrual cycles.[ 30 ] Adenomyosis is more common in multiparous women and those who have undergone uterine surgery, such as dilation and curettage, Cesarean delivery, or myomectomy. Physical exam may reveal an enlarged, tender uterus. Diagnosis is made via TVUS or MRI. Progesterone‐based therapy is first line, with LNG‐IUD being the most effective for adenomyosis. If symptoms persist, surgical intervention with hysterectomy is warranted.[ 30 ] Leiomyomas (fibroids) are a common cause of heavy menstrual bleeding in reproductive‐age women. Their prevalence is higher among African‐Americans, who are disproportionately affected by ESRD.[ 49 ] Symptoms include heavy, painful, and/or prolonged menstrual bleeding, as well as bulk symptoms like pelvic pressure, pain, constipation, and urinary incontinence. In KTR, large fibroids can damage the graft through ureteral obstruction.[ 49 ] Exam may demonstrate an irregularly enlarged uterus. Fibroids can be diagnosed via pelvic ultrasound; with hysteroscopy, MRI, and saline‐infusion sonography as subsequent modalities for further characterization.[ 30 ] Asymptomatic fibroids require no treatment but should be monitored via TVUS due to potential for enlargement and graft impact.[ 32 ] Medical therapies (CHC, progestins) are first‐line treatments for symptomatic fibroids without graft dysfunction. Surgical treatment is necessary for refractory symptoms, bulk symptoms, or graft risk. Fertility‐preserving options include hysteroscopic and laparoscopic procedures such as myomectomy. Fibroid embolization and radiofrequency ablation are generally reserved for women desiring uterine‐sparing—though not necessarily fertility‐sparing‐treatment. Hysterectomy is definitive therapy for those not desiring future fertility.[ 49 ] Endometrial hyperplasia typically presents as heavy or irregular bleeding and is more prevalent in KTR.[ 26 ] A small, retrospective single‐center study of KTR with AUB undergoing dilation and curettage from 1999 to 2004 reported a 69% rate of hyperplastic lesions compared with 33% in non‐transplanted patients evaluated for the same indication.[ 50 ] These KTR were receiving calcineurin inhibitor‐based immunosuppression, with a higher prevalence in those on cyclosporine compared to tacrolimus (71% vs. 29%).[ 50 ] More recent data from a small retrospective study of SOT with AUB (1986–2017) reported a 17.2% prevalence of endometrial hyperplasia, with all cases occurring in KTR.[ 26 ] The prevalence of hyperplasia also varied by immunosuppressive regimen, with no cases of hyperplasia in patients receiving mTOR inhibitors compared to 14.1% in those on a cyclosporine‐based regimen.[ 26 ] These estimates should be interpreted with caution, as they reflect highly selected cohorts of symptomatic women undergoing diagnostic evaluation and may not be generalizable to all KTR. However, they suggest that immunosuppressive regimen may influence the risk of endometrial hyperplasia in this population. CKD also contributes to elevated risk for endometrial hyperplasia, with CKD‐driven HPG‐axis dysfunction causing unopposed estrogen stimulation.[ 3 , 42 , 48 ] Other causes of unopposed estrogen, like obesity, anovulation, and nulliparity, increase this risk.[ 32 ] Endometrial hyperplasia is diagnosed through endometrial sampling and classified by the presence of atypia. First‐line treatment of hyperplasia without atypia in KTR is LNG‐IUD, which leads to regression of the hyperplastic lesion.[ 50 ] Some experts advocate for adjustment of immunosuppressive regimen, including consideration of mTOR inhibitors.[ 26 ] If hyperplasia persists, or if relapse occurs after completion of medical treatment, hysterectomy is recommended. Some experts suggest a period of progestin treatment for 6 months before proceeding to operative treatment in KTR, compared to the 12‐month guideline for the general population.[ 42 ] In patients with endometrial hyperplasia with atypia, hysterectomy is first‐line treatment. KTR have both bleeding and thrombotic risks. ESRD is associated with platelet dysfunction, vessel damage, and clotting factor deficiencies.[ 51 ] There is conflicting evidence on the effect of kidney transplant on bleeding and thrombotic risk.[ 32 ] One etiology for increased bleeding risk in KTR, and thus a potential etiology for AUB, is posttransplantation thrombocytopenia (PTTCP). In a cohort of 2118 KTR, 8.9% developed PTTCP, with bleeding in one‐third of those patients.[ 52 ] Evaluation includes CBC with hematology consultation as needed. Women are often amenorrheic and anovulatory prior to transplant due to HPG‐axis disruption.[ 1 ] Resumption of ovulation typically occurs within 1–12 months posttransplant.[ 4 ] However, due to persistent dysregulation of the HPG‐axis, many of these cycles are anovulatory and can result in heavy and irregular menstruation. While often related to persistent HPG‐axis disruption, conditions such as polycystic ovarian syndrome (PCOS) and thyroid dysfunction may also lead to anovulation. PCOS is the most common endocrinopathy among women in the United States and results in androgen excess and insulin resistance, leading to anovulation and unopposed estrogen.[ 30 ] Diagnosis is based on the Rotterdam criteria, stating that patients must have at least 2 of the following: clinical or chemical findings of hyperandrogenism, irregular menses, and/or polycystic ovaries on imaging.[ 53 ] CHC are the first‐line treatment for resumption of ovulation and regulation of menses in appropriate KTR.[ 54 ] Progestin‐only therapy will prevent endometrial hyperplasia and potential AUB but will not treat underlying anovulation. Metformin is a common therapy to aid in resumption of menses in patients with PCOS.[ 54 ] Multiple studies demonstrate the safety of metformin in KTR, with no associated risk for drug‐induced lactic acidosis.[ 55 ] Furthermore, weight loss can improve metabolic outcomes and restore ovulation. Thyroid disorders are more prevalent in KTR than in the general population and can also cause AUB.[ 3 , 4 , 56 ] Hypothyroidism tends to cause heavy and irregular menstrual bleeding, while hyperthyroidism more often causes infrequent or light menses.[ 30 ] Changes in vital signs, weight, and energy can alert the clinician to possible thyroid dysfunction and pursuit of appropriate lab work; treatment restores normal menstruation. Pelvic pain is a common complaint in reproductive‐age women and can arise from gynecologic and non‐gynecologic pathology. Differentiating acute from chronic pain is important due to the urgent need for intervention in many causes of acute pain, such as ectopic pregnancy, adnexal torsion, sexually transmitted infections (STI), and appendicitis.[ 57 ] Chronic pelvic pain, defined as pelvic pain lasting more than 6 months, has a broad differential and risk of morbidity.[ 58 ] History should include information about the relationship of the pain to menses, aggravating and alleviating factors, quality, and location. Exam, lab work, and imaging can be tailored based on history. Common gynecologic causes of chronic pelvic pain are endometriosis, leiomyomas, and a history of pelvic inflammatory disease (PID). Post‐surgical pain, such as from adhesions, may complicate diagnosis and exacerbate other chronic pelvic pain. Evidence for transplant‐specific evaluation and management of these pathologies is extremely limited, and thus, recommendations for KTR are largely extrapolated from general population data and expert consensus. Endometriosis can manifest as cyclic pain with menses and presents similarly in KTR as in the general population. No data exists on the prevalence of endometriosis in KTR or other SOT patients. Pathogenesis of endometriosis is complex, consisting of local and systemic inflammation in conjunction with paradoxical immunosuppressive features that allow ectopic tissue to evade immune clearance.[ 59 , 60 ] So although KTR are chronically immunosuppressed, there is a paucity of data on whether this is disease modifying either way.[ 59 ] Patients with endometriosis may report dyspareunia, back pain, and/or dyschezia.[ 61 ] Physical exam may demonstrate tenderness in the posterior vaginal fornix, uterine motion tenderness, a fixed and retroverted uterus, and/or tender adnexal masses. Lab tests are low yield in endometriosis and imaging findings do not provide definitive diagnosis; laparoscopic visualization is considered the gold standard for diagnosis. However, given the associated risks of surgery in KTR, empiric treatment of suspected cases is often warranted. Medical treatment options for KTR include progestins as well as CHC.[ 61 ] If endometriosis is refractory to medical management, surgical treatment can be considered; however, sparse literature exists on its effectiveness in KTR specifically.[ 62 ] PID can cause pelvic pain, both acutely and from subsequent adhesions. Although STI occur at lower rates in KTR compared to the general population [ 63 ], STI are common in reproductive age women generally. Routine posttransplant care should include counseling on STI prevention with barrier use, abstinence, and/or regular STI testing in sexually active patients. In immunocompromised patients, PID may present with absent or atypical symptoms and carries an increased risk of sepsis.[ 63 ] History should include sexual history and evaluation for symptoms such as dysuria, vaginal discharge, pelvic pain, or fever. Physical exam should assess for cervical‐motion, uterine, and adnexal tenderness. Empiric treatment is warranted for patients with pelvic pain and tenderness, after excluding other causes. Laboratory workup should include pregnancy test, STI screening, urinalysis, and vaginal cultures. Imaging with TVUS to assess for tubo‐ovarian abscess, free pelvic fluid, and/or thickened fallopian tubes may be helpful. Computed tomography and diagnostic laparoscopy are also helpful; however, diagnostic evaluation should not delay empiric treatment, particularly in immunocompromised patients.[ 64 ] No transplant‐specific guidelines exist for treatment of PID but guidelines for general population apply to other groups of immunocompromised patients and should likewise be used for KTR. For mild‐to‐moderate PID, outpatient management with a broad‐spectrum regimen such as ceftriaxone, doxycycline, and metronidazole is typical. Hospitalization, placement of drains, and intravenous therapy should be considered for those with tubo‐ovarian abscess, severe PID, or who fail outpatient management.[ 65 ]