Sexual and reproductive health screening and counseling in adolescent and young adult transplant recipients

Adolescents and young adults with and without chronic illnesses partake in risk‐taking behavior. Clinicians in transplant clinics should be aware of the prevalence of risk‐taking behavior in their adolescent and young adult solid organ transplant patients in order to provide complete care. Creating an environment where teens and young adults feel comfortable discussing risky behavior is important and includes creating a privacy policy and increasing comfort of the healthcare provider in asking sensitive questions. This review is intended to help the providers in the transplant clinic screen for and counsel about risk‐taking behaviors with their adolescent and young adult patients, specifically around sexual and reproductive health.

Risk behavior surveillance system (YRBS) surveys high school students throughout the country on health-related behavior questions on sexual health, substance use, and other risk-taking behavior. 2roughout the past 10 years, some risk behaviors have been on the decline (recent sexual activity and current alcohol use), and some risk behaviors are on the rise (experiences of violence and suicidal ideation). 3gardless of the trends, risks can have consequences.In the general population, AYA are more likely than adults over 25 years to binge drink, smoke cigarettes, have casual sex partners, engage in violent and other criminal behavior, and have fatal or serious automobile accidents, the majority of which are caused by risky driving or driving under the influence of alcohol.Because many forms of risk behavior initiated in adolescence elevate the risk for the behavior in adulthood (e.g., drug use), and because some forms of risk-taking by adolescents put individuals of other ages at risk (e.g., reckless driving, criminal behavior), public health experts agree that reducing the rate of risk-taking by AYA would make a substantial improvement in the overall well-being of the population. 4e following are not specific recommendations for the transplant provider but the information is available in general and form standard of care for general care of AYA patients.Some data focuses on adolescents (generally 12-18 years of age) and some focus on young adults (generally 18-24 years of age).

| CONS ENT AND CONFIDENTIALIT Y
In order to get AYA patients to disclose risk-taking behaviors that may impact their health and well-being, the first step is to set up a clinic privacy policy.Studies have shown that concerns about privacy decreased willingness of AYA in the general population to seek healthcare and communicate concerns. 5In this study, 17% of surveyed teens reported foregoing healthcare because of concerns parents would find out.Assurance of confidentiality increased willingness to disclose sensitive information from 39% to 46.5%.However, 67% of teens who were assured confidentiality were willing to return for future visits vs. 53% if no mention of confidentiality.In looking at sexual health in particular, 50% of the surveyed sexually active females <18 years old would stop using the clinics if parental notification for prescription contraceptives were mandatory.An additional 12% reported that they would delay or discontinue the use of specific services, such as services for sexually transmitted infections if parents were notified.Only 1% of the teens reported that they would also stop having intercourse. 6 contrast, parents of adolescents in the general population surveyed overwhelmingly believe that the doctor should inform them about all conversations, even when the teen preferred the parent not be told. 7Mothers have reported the belief that confidentiality between their daughters and clinicians might promote risky behavior and undermine their ability to protect their daughters.Research also indicates that parents hold conflicting views about confidentiality.
Parents have been shown to support confidentiality between adolescents and doctors, yet hold simultaneous desires to be provided with details of what is discussed.Parents have also indicated support for parental notification laws, yet were concurrently able to identify a range of negative effects associated with these. 8Navigating the balance of autonomy, independence, and self-discovery may be even more complex with adolescent SOT recipients due to involvement of the parent/guardian in the complex medication regimens and frequent appointments necessary to maintain the patient and allograft health.
Despite the necessary involvement of the parent/guardian in the healthcare of an adolescent SOT, it is not reasonable to expect AYA patients to discuss sensitive and personal information unless confidentiality can be assured.All AYA and families should be told about confidentiality at the beginning of the first visit.
Interviewing the AYA patient in the room alone (i.e., without a parent/guardian present) for at least a portion of the visit is the standard of care for all healthcare visits.The terms of a confidential visit should be explained to the patient and parent; all information disclosed by the adolescent remains confidential (within the confines of the state's confidentiality laws) unless he or she reveals a risk of rendering harm to himself or herself or others, such as with suicidal or homicidal ideation.Specific state laws and policies can be found on the Guttmacher Institute website (Guttm acher.org).
It is important to discuss the clinic's confidentiality policy with patient and parent/guardian before it becomes an issue and to make sure that patient and parent both have opportunity to discuss concerns.A possible appointment set up to encourage privacy is shown in Table 1.Physicians should discuss confidentiality with the patient and the parent or guardian, if present, at the first clinic visit.The clinician should stress that they have the same goal as the parent/guardian: the health and well-being of the patient.
While physicians should respect patients' privacy and confidentiality, they should also encourage communication between the patient and their parents.Parental support can be a valuable tool in helping AYA meet their healthcare needs, especially with SOT recipients.

| HOW TO INTERVIE W AYA
Healthcare providers, like those in any other profession, have likely developed a set of beliefs regarding particular situations based on knowledge, training, experience, and personal views.
Healthcare providers interfacing with AYA may be confronted with situations where their own particular belief system may be tested and assumptions may be challenged.These assumptions may include patients live in a home with two parents, all adolescents go to school on a regular basis, all AYA are heterosexual, and AYA with chronic illnesses do not engage in risk-taking behavior.These assumptions can lead to patients receiving poor | 3 of 10 CODY treatment, receiving inaccurate diagnoses, or experiencing delays in diagnosis.It is important for clinicians not to make assumptions based on age, appearance, or any other factor, but rather to ask nonjudgmental questions in a respectful, caring fashion.It is also important for clinicians to increase their comfort in asking sensitive questions by practicing with every patient; if a healthcare provider is uncomfortable talking about risk-taking behavior, the patient will be uncomfortable too.
Here are some tips for discussing sensitive topics with AYA patients in the general population, that can be applied to the AYA transplant population: 1. Make your patient feel comfortable by establishing a rapport before asking sensitive questions.
2. Normalize the questions.Let your patient know that you ask everyone these questions.
3. Start with less-sensitive questions and transition into asking more-sensitive questions.
4. Pose your questions in a nonjudgmental manner.
5. Ask open-ended questions instead of yes/no questions (e.g., "Tell me about your alcohol use," instead of "Do you drink alcohol?") 6. Try not to react overtly, even if you feel uncomfortable or embarrassed.Pay attention to your body language and posture.
7. Rephrase your questions or briefly explain why you are asking a question if a patient seems offended or reluctant to answer.8. Ensure that you and your patient share an understanding of the terms being used, to avoid confusion.If you are not familiar with a term your patient used, ask for an explanation.
The HEADSSS assessment (Table 2) is an interview instrument created to help a clinician get a thorough psychosocial history for AYA patients in the general population but can be applied to the AYA transplant population. 9The interview is set up to go from less invasive questions (living situation) to more-sensitive questions (sexual health and suicide/mental health).

| G ENDER IDENTIT Y
According to The Williams Institute report, 10 700 000 AYA identify as transgender or nonbinary in the United States or about 1.4% of the US population ages 13-24 years.Adolescents ages 13-17 comprise about 18% of the transgender-identified population in the U.S. It is not known the number of AYA transplant recipients that identify as transgender or nonbinary.Research shows that when a person's gender identity is not affirmed, it leads to higher rates of anxiety, depression and suicidality in trans, nonbinary, genderqueer, and gender-diverse AYA. 11Providing gender-affirming care improves mental health and increases positive outcomes in AYA.To create an environment where a patient feels comfortable sharing their gender identity, a clinician should: 1. Introduce self with personal pronouns.
2. Ask patient for their correct pronouns and terminology.Use the pronouns they share and support that patient's current gender identity, even if their anatomy does not match that identity.
3. Make sure clinic paperwork is gender-inclusive.

| BODY IMAG E AND E ATING DISORDER S
Adolescence is a time of rapid growth and development, both physically and emotionally.AYA often express specific concerns about their change in appearance during adolescence.According to the 2021 YRBS, about half of the surveyed teenagers admitted to trying to lose weight. 3In fact, eating disorders are the third most common chronic condition of adolescence. 12A with chronic illnesses often report body image disturbances.
For instance, medical treatments may delay normal growth and result in shorter stature, delayed onset of puberty, and nutritional concerns 13 that can lead to body dissatisfaction.Body dissatisfaction TA B L E 1 Potential structure of clinic visits for adolescent patients to promote privacy.can have harmful consequences, such as the development of disordered eating behaviors and eating disorders. 14T recipients are no different.Like those with other chronic illnesses, they need to balance their desire to adhere to medical treatment plan with a body image that may be adversely affected by treatments and immunosuppressive medications such as steroids and cyclosporine.It may be difficult for AYA to accept the weight gain and Cushingoid features secondary to steroids or the hirsutism and gingival hyperplasia associated with cyclosporine. 15Henning et al. designed a questionnaire comparing young adult renal transplant recipients to young adults with juvenile-onset diabetes to assess height and disability, as well as a simple and subjective assessment of social activities. 16Young adults with end-stage renal disease and subsequent transplant reported fewer significant romantic relationships and more sexual problems than those with juvenileoutside diabetes and were more likely to believe their renal disease had adversely affected their social life, specifically because of short stature, obesity, and other medication side effects.
To inquire about body image, one question that can be helpful is "How do you feel when you look in the mirror?"The answer to this question can give the clinician an opening to question the patient about disordered eating behaviors, including skipping meals, binging, self-induced vomiting, laxative use, diuretic use, cleanses, or exercise dependence.

| MEN S TRUAL HE ALTH
Menstruation is a significant quality of life factor for AYA in the general population, and problems with menstruation can be a cause of school/work absence as well as other psychosocial impairments.
Questions for a thorough menstrual history include  | 5 of 10

CODY
In the United States, the median age of menarche is 11.9 years. 17though there has been minimal research about the topic, the available data show that pubertal delay is common in patients receiving SOT, with girls experiencing menarche at least 1-2 years later than average. 18,19Among AYA who are postmenarchal at time of transplant, menstrual abnormalities associated with liver or kidney dysfunction are likely to normalize after transplantation.
The most prevalent gynecological condition in people who menstruate is dysmenorrhea, which is a medical condition characterized by severe uterine pain around the time of menstruation, manifesting as pelvic or cyclic lower abdominal pain radiating to the back and thighs. 20Its frequency in the general population ranges from 16.8% to 81%, with rates as high as 90% 21 ; the prevalence of dysmenorrhea has not been studied in AYA SOT recipients. 22armacological treatment involves nonhormonal therapy and hormonal therapy.Nonhormonal medical therapy consists of acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs), 21 which may not be a suitable option for an SOT recipient due to a number of factors, including liver or kidney dysfunction.Hormonal therapy is composed of estrogen-progestin combined hormonal contraceptives (CHC) and progestin regimens.These options will be discussed briefly below in the contraception discussion.
Primary dysmenorrhea can also be managed with a variety of alternative nonpharmacological methods, including self-care strategies, such as exercise, rest, dietary modifications, and cold and heat therapy, 22 although reported effectiveness of these methods is variable. 23,24

| HOW TO CONDUC T A THOROUG H S E XUAL HIS TORY (G ENDER IN CLUS IVE )
Results of the 2021 CDC YRBS 3 showed that there has been a decrease in number of adolescents who are sexually active prior to graduating high school (possibly related to COVID restrictions); however, 30% of those surveyed were sexually active by 18 years old and 6% report having four or more sexual partners, yet less than half report using a condom during their last sexual encounter.Over 20% report using alcohol or other drugs prior to their last sexual encounter.Not surprisingly, 25% of sexually active adolescents are diagnosed with an STI before graduating high school. 25nce AYAs with chronic illnesses may be more socially isolated than their peers, they may be perceived as having fewer romantic relationships and sexual desires than their healthy peers. 26For example, subspecialty physicians have been found to underestimate the proportion of their female adolescent patients with chronic disease who engage in risk-taking behavior, including sexual activity. 27It should be assumed that AYA transplant recipients, like other chronically ill AYA, are often sexually active.In a US survey for pediatric nephrologists about perceptions and practice patterns regarding reproductive health counseling, the majority (83%) of respondents believed STI risk among adolescent kidney transplant recipients is similar to or higher than healthy teens, 28 however, less than half of the respondents routinely inquired about sexual activity or counseled about safer sex.
The Center for Disease Control and Prevention (CDC) created the 5 "P" assessment tool to assess STI risk, but this tool serves as a template for a thorough sexual history (See Table 3). 29

| S E XUAL FUN C TI ON AND LIB IDO
End-stage organ failure is associated with impaired hypothalamicpituitary-gonad function marked by decreased testosterone levels in people with testes, 30,31 leading to symptoms such as difficulty in erection, loss of libido, premature ejaculation, and oligospermia.
In people with ovaries, the impairment in hypothalamic-pituitarygonadal axis can lead to menstrual irregularities as mentioned above but also decreased or absent libido. 31In adults, the sexual dysfunction and loss of libido associated with end-stage organ disease often resolves after transplantation 32,33 but not always. 34Research has not been conducted into the sexual function or libido of AYA SOT recipients.

| S E XUALLY TR AN S MIT TED INFEC TIONS
The recent CDC Sexually Transmitted Disease Surveillance Report continues to demonstrate high numbers of infections with sexually transmitted diseases, affecting all genders and all racial and ethnic groups, with the highest burden occurring in AYA.Although individuals 15-24 years old account for only 13% of the sexually active US population, 35 they account for 50% of the STI diagnoses, including over 40% of gonorrhea and 63% of chlamydia cases. 36These numbers underestimate many asymptomatic STIs in AYA who do not undergo appropriate screening.
Sexually active adolescents may be more vulnerable to STI than their adult counterparts because of biologic factors.For example, adolescents may be more susceptible than adults to chlamydial infections after exposure to Chlamydia trachomatis due to cervical immaturity/ectopy. 37It is possible that being immunocompromised can increase the likelihood even more that exposure to a sexually transmitted disease will lead to infection.Only a few reports can be found in the literature about STI in SOT recipients, and they are limited by the low number patients. 38,39A small cross-sectional review of 49 adolescent renal transplant recipients found a 30% STI prevalence in targeted screening of symptomatic patients compared to 15% prevalence in the general adolescent clinic population offering universal screening. 40In the review of a large database of SOT recipients, the highest frequency of STI was seen among patients transplanted during adolescence, 41 suggesting that screening and counseling efforts should be focused on AYA.STIs can be severe and difficult to eradicate in immune-suppressed patients.
Chlamydia, caused by the bacteria Chlamydia trachomatis, is the most frequently reported bacterial sexually transmitted infection in the United States. 42It is difficult to account for many cases of chlamydia since many people with the infection have no symptoms and do not seek testing.Chlamydia is most common among AYA; two-thirds of new chlamydial infections occur among youth aged 15-24 years. 43Estimates show that 1 in 20 sexually active women aged 14-24 years has chlamydia. 44norrhea, caused by Neisseria gonorrhoeae, is the second most common notifiable sexually transmitted infection in the United States for that year; in 2021, a total of 710 151 cases of gonorrhea were reported to the CDC.Rates of reported gonorrhea have increased 118% since their historic low in 2009. 39e United States Preventive Service Taskforce (USPSTF) releases recommendations for a number of public health priorities, including STIs.The USPSTF recommends screening for Chlamydia trachomatis and Neisseria gonorrhoeae in all sexually active women 24 years or younger. 45Guidelines also recommend regular screening for males who have sexual intercourse with other males but are less clear when it comes to males who do not have sex with males.
In our clinic, we screen all sexually active SOT recipients based on sexual behaviors, regardless of gender; follow-up screening for STIs occurs every 6 months, and STI testing whenever there are complaints of vaginal or penile discharge, dysuria, or other genitourinary TA B L E 3 The Center for Disease Control's 5 P's approach to taking a thorough sexual history., external or internal condoms-also known as male or female condoms-dental dams, etc.) • How often do you use this/these method(s)?More prompting could include specifics about: • Frequencies: sometimes, almost all the time, all the time • Times they do not use a method.• If "sometimes," in which situations, or with whom, do you use each method?• Have you received human papilloma virus (HPV), hepatitis A, and/or hepatitis B shots? • Are you aware of preexposure prophylaxis or PrEP, a medicine that can prevent HIV? Have you ever used it or considered using it?
Past history of STI • Have you ever been tested for STIs and HIV? Would you like to be tested?
• Have you been diagnosed with an STI in the past?When?Did you get treatment?
• Have you had any symptoms that keep coming back?
• Has your current partner or any former partners ever been diagnosed or treated for an STI? Were you tested for the same STI(s)?Do you know your partner's (or partners') HIV status?
Pregnancy intention • Do you think you would like to have (more) children at some point?
• When do you think that might be?
• How important is it to you to prevent pregnancy (until then)?
• Are you or your partner using contraception or practicing any form of birth control?Would you like to talk about ways to prevent pregnancy?Do you need any information on birth control?
e USPSTF recommends that clinicians screen for HIV infection in patients aged 15-65 years at least once, regardless of risk factors. 47Younger adolescents and older adults who are at increased risk of infection should also be screened.Additional risk factors for HIV infection include having anal intercourse without a condom, having vaginal intercourse without a condom and with more than one partner whose HIV status is unknown, exchanging sex for drugs or money, having other STIs or having a sex partner with an STI, and having a sex partner who is living with HIV or is in a high-risk category.Persons who request testing for STIs, including HIV, are also considered at increased risk.Although the acquisition of HIV through sexual practices in a SOT recipient may be rare, it is not impossible.Fortunately, SOT recipients who acquire HIV can have a good response to antiretroviral therapy. 48eexposure prophylaxis (PrEP) involves administering antiretroviral medications to HIV-uninfected, at-risk individuals to lower their risk of sexual HIV acquisition.PrEP is approved for AYA who are at risk for HIV due to sex or IV drug use.One important thing to note is that many immunosuppressive medications are metabolized in the liver through the cytochrome P450 pathway, specifically CYP3A4 and CYP3A5.These immunosuppressive medications are affected by agents that induce or inhibit this enzyme system; fortunately, PrEP medications are not metabolized through these pathways.A notable concern for the use of some types of PrEP is the potential for kidney toxicity, so their use should be considered carefully.

| H UMAN PAPILLOMA VIRUS
Vaccination with human papilloma virus (HPV) is important for all AYA, but especially important for SOT recipients. 49SOT recipients are more likely than immunocompetent patients to have high-risk oncongenic HPV subtypes 16 and 18, 50 and have substantially increased risk of anogenital neoplasia. 51Renal transplant recipients also have increased risk of HPV-related anogenital warts, especially vulvar and perianal warts, compared with an immunocompetent control group. 52

| CONTR ACEP TI ON
Neither transplantation nor immunosuppressant medications decrease fertility, and conception has been seen as early as 3 weeks after a liver transplant. 55Pregnancy is not contraindicated but is high risk for the patient due to potential for premature birth and fetal abnormalities related to immunosuppressive medications.
Complications such as preeclampsia, pregnancy-induced hypertension, gestational diabetes, ectopic pregnancy, still birth, low birth weight, and preterm birth are more common in pregnant women with kidney transplants.It should be carefully planned and avoided for at least 1-2 years posttransplant. 56tailed recommendations for contraception based on patient goals and healthcare needs are beyond the scope of this review and the reader is referred to Shah et al. 57 Table 4 lists the CDC medical eligibility criteria for contraception use in SOT recipients (complicated vs uncomplicated). 58Complicated SOT includes graft failure (acute or chronic), rejection, or cardiac allograft vasculopathy.As mentioned above, many immunosuppressive medications are metabolized in the liver through the CYP3A4 and CYP3A5 pathways and are affected by agents that induce or inhibit this enzyme system.Combined hormonal contraceptives (CHC) inhibit the CYP3A4 pathway, 59 and their use may increase the bioavailability of other medications that are metabolized through this pathway, such as cyclosporine, tacrolimus, and sirolimus.
Since SOT is associated with increased risk for adverse health events as a result of pregnancy, emergency contraception (EC) is a necessary option to discuss.EC can be used up to 3-5 days after an episode of unprotected sex. 60Oral levonorgestrel is available over the counter without a prescription in some states.Ulipristal acetate requires a negative pregnancy test and a prescription.Note that effectiveness of these methods may be impacted by weight of the patient.
Similar to some other contraceptives, levonorgestrel and ulipristal utilize the CYP450 3A4 pathway, so concurrent use with enzyme inducers, such as some immunosuppressants, may decrease their effectiveness. 61The copper IUD can be placed regardless of weight up to 5 days after unprotected sex.New studies are showing that levonorgestrel IUDs can also be used as emergency contraception. 62

| CON CLUS ION
AYA engage in risk-taking behaviors to find out who they are, not necessarily to be disobedient.In the process of taking healthy risks, they will gain confidence, courage, and the ability to make plans and resist impulses-all important skills they will need in life.SOT recipients engage in risk-taking behavior just like their peers.It is important for all healthcare providers, including clinicians on the transplant team, to assess for these risks and counsel their SOT patients about the unique impact these risks may have on their health.

1 .
Age at menarche 2. Description of menses a. Regularity b.Duration c. Flow d.Associated symptoms: headaches, dysmenorrhea, mood changes, skin changes 3. Impact of menses on life-missing school, missing activities 4.Last menstrual period TA B L E 2 The HEADSS assessment and some sample questions for each category.
Partners• Are you currently having sex of any kind-oral, vaginal, or anal-with anyone?(are you having sex?) • When was your last sexual activity?• If not, have you ever had sex of any kind with another person?• In recent months, how many sex partners have you had? • What is/are the gender(s) of your sex partner(s)?• Do you or your partner(s) currently have other sex partners?Practices • I need to ask some more specific questions about the kinds of sex you have had over the last 12 months to better understand if you are at risk for sexually transmitted infections or STIs.Would that be OK? • We have different tests that are used for the different body parts people use to have sex.What kinds of sexual contact do you have, or have you had?What parts of your body are involved when you have sex?• Do you have genital sex (penis in the vagina)?• Anal sex (penis in the anus)?• Oral sex (mouth on penis, vagina, or anus)?• Are you a top and/or bottom?• Have you or any of your partners used drugs?• Have you exchanged sex for your needs (money, housing, drugs, etc.)? • Compassionate but direct questions about the possibility of abuse, sexual assault, or other nonconsensual sex should be included • If you use prevention tools, what methods do you use? (e.g.
Evidence specific for renal, heart/lung,

Table 5
lists the medical eligibility criteria for the use of different EC in SOT recipients.15|FUTURE DIREC TIONSThis review highlights potential areas of research to better understand the needs of AYA SOT recipients.There are few studies on the risk-taking behaviors of AYA SOT recipients, in part due to the low number of patients.Centers that do SOT transplants in AYA patients should collaborate to get the number of patients.