Intimacy changes after a cancer diagnosis. Both male and female survivors can experience significant sexual dysfunction, pain with sex, loss of desire, and a slew of other clinical and psychological sequelae. To make matter worse, sexual function is often not discussed by patients and their providers, due to mutual embarrassment, lack of training, or the feeling by many patients that they should simply be grateful for their lives after cancer.

However, according to John P. Mulhall, MD, and Tami Rowen, MD, sexual health is a crucial component of a person’s feeling whole again after a cancer diagnosis and treatment. The topic should not be taboo, nor should patients apologize for wanting to address it. At the 2019 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) 2019 Annual Meeting in San Francisco,¹ Drs. Mulhall and Rowen discussed common conditions and treatment strategies for addressing sexual function in male and female survivors and how providers can confidently help these patients redefine sex after cancer.

Sexual Dysfunction in Men

“It’s not rocket science to understand how cancer therapy and cancer diagnosis cause sexual problems,” said Dr. Mulhall, a urologic surgeon and Director of the Male Sexual and Reproductive Medicine Program at Memorial Sloan Kettering Cancer Center in New York. “I see myself as a sexual medicine physician. And my job is to help the patient, or couple where one exists, to resume satisfactory sexual relations.” According to Dr. Mulhall, physicians should discard the problematic mindset that patients should be happy once they’re cured of their cancer in favor of one that sees maintaining sexual and reproductive health as critical components in a holistic approach to wellness.

I see myself as a sexual medicine physician. And my job is to help the patient or couple … to resume satisfactory sexual relations.

— John P. Mulhall, MD

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Sexual dysfunction in male cancer survivors can be caused by a variety of treatments or psychological factors and may include erectile dysfunction, low libido, failure to ejaculate, delayed or painful orgasm, and sexual incontinence. Once these sequelae occur, men can spiral downward into experiencing loss of sexual confidence and self-esteem, reduced sexual satisfaction, sexual avoidance (often mistaken for loss of sex drive), and changes in relationship satisfaction.

Informing patients about these potential side effects is crucial, particularly after radical prostatectomy. “I’ve been in business 23 years, and every week there’s a 55-year-old man in my office, tears in his eyes, saying, ‘I don’t know why I did it,” explained Dr. Mulhall. “‘I would have preferred to have lived with my cancer than be the way I am: incontinent and stuck on penile injections for the rest of my life because of the erectile dysfunction related to my operation.’”

Optimal Health Care in the Sexual Medicine Space

According to Dr. Mulhall, the “big sins” in sexual health care are apathy, ageism, projection, judgment, and intolerance. “You should not project your mores, your judgment, or your values on your patient,” he said. “[Sex] might be a critically important cornerstone of your patient’s relationship, and it’s our job to facilitate his return to that.”

Optimal outcomes require strongly informed consent before treatment, which requires that the clinician provide realistic expectations about the effectiveness and side effects of treatment. If curing a patient’s cancer will result in low testosterone or permanent fertility problems, those conversations should be held early on, noted Dr. Mulhall.

Lack of communication is a major barrier to good sexual health care. The Global Study of Sexual Attitudes and Behaviors study revealed that about 12% to 14% of men and women were asked by their family doctor about their sex life in the past year.² When patients were asked why they did not bring it up themselves, they cited not wanting to embarrass their physician.

“We are not doing a very good job and may be sending off vibes to our patients that we’re not very comfortable with this topic,” said Dr. Mulhall. “But how could we be comfortable when we get an average of about 2 hours of education on this topic during medical school?”

All too often, patients have unrealistic expectations of sex after cancer. The single most obvious consequence of having a radical prostatectomy is failure to ejaculate, but many men who have undergone the operation were not made aware of that fact, he said.

Dr. Mulhall urges physicians to set realistic expectations with patients. They should discuss the prevalence of major sexual problems and the chronology of recovery as well as strategies to treat adverse events and minimize long-term effects. And patients should be referred to sexual medicine clinicians before cancer treatment, according to Dr. Mulhall.

“Your patients are going into treatments—surgery, chemotherapy, hormone therapy—perhaps with their eyes not fully open,” he added. “We need to rethink how we’re communicating with our patients.”

The Issue of Testosterone

In the United States, testosterone prescriptions have nearly tripled in recent years. However, about one-third of patients on testosterone therapy do not meet the criteria for receiving testosterone, and one-quarter of men on testosterone therapy have never had their testosterone level checked. “This is absolutely mind-boggling to me,” stated Dr. Mulhall. “And even more mind-boggling is that 40% of men who are currently on treatment aren’t having their testosterone levels checked. This is absurd medically and just negligent.” 

Dr. Mulhall implores physicians to measure testosterone levels, even in the absence of symptoms of low testosterone. Without knowing a patient’s baseline, it is impossible to know what effect treatment has had on his testosterone level.

Many men in need of testosterone therapy are not receiving it, largely due to physician anxiety in prescribing it, he said. Despite the conception that testosterone therapy might be associated with major adverse cardiac events, there is no definitive evidence linking it to venothromboembolic events, and perhaps more important, low testosterone is a risk factor for major cardiovascular events.

“Low testosterone is not just about low sex drive, loss of energy, and bad erections,” said Dr. Mulhall. “It’s about bones, heart, osteoporosis, diabetes development, and then cardiac events.”

Finally, according to Dr. Mulhall, a man who wants to be fertile now or possibly in the future should never be given testosterone. “You must document that a man you’re giving testosterone to is not interested in fertility,” he emphasized. “It doesn’t matter if he’s 65 years of age. It is important to ask—not based on age—what his interest is.”

Addressing Vasomotor Symptoms in Women

A multitude of factors contribute to female sexuality after cancer, and the priorities are not the same for all women. For some, the main priority is not having the cancer come back; for others, it’s improving their quality of life and regaining sexual response, according to Dr. Rowen, an obstetrician/gynecologist and Director of the Female Sexual Health Program at the University of California, San Francisco.

Menopausal vasomotor symptoms are often more severe in cancer survivors. Premenopausal women with normal menstrual function may have ovarian shutdown with chemotherapy, and postmenopausal women taking menopausal hormone therapy to manage these symptoms tend to abruptly stop when diagnosed with breast or gynecologic cancer. Vasomotor symptoms are also common with hormonal drugs such as tamoxifen or aromatase inhibitors.

Treatment options for menopausal hot flashes in female survivors often include hormonal therapies in appropriate patients: a combination of estrogen and progesterone if the patient has an intact uterus and estrogen alone in the case of prior hysterectomy.

Any woman who will receive radiation to the pelvis should be counseled on the use of dilators to effectively manage vaginal stenosis.

— Tami Rowen, MD

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“Almost every woman who comes to me, regardless of the cancer type she has, is convinced that hormones will cause cancer or did cause her cancer,” said Dr. Rowen. “The only patients we really need to be concerned about putting on hormone therapy are those who have hormone-sensitive cancer.”

If physicians prescribe nonhormonal treatments, such as antidepressants, gabapentin, or selective serotonin-reuptake inhibitors, Dr. Rowen suggests starting with the lowest dose possible to avoid discontinuation. For instance, with venlafaxine, the best studied antidepressant for this indication, beneficial effects are seen with doses lower than those typically used for depression (75 mg/d in divided doses). These treatments also have their own side effects, such as decreased appetite, fatigue, nausea, and sexual disturbances, so patients should be counseled accordingly.

First Step: Treating Vaginal Dryness

According to Dr. Rowen, many women also express desire for treatment of vaginal dryness that does not involve hormones. Effective vaginal moisturizers and lubricants are available, but it is important to make sure patients understand the difference between them: lubricants should be used as needed, during sexual activity, whereas moisturizers are intended for ongoing use. However, she noted, many of the vaginal moisturizers and lubricants available in the United States are not pH-balanced or balanced for osmolality and thus not necessarily healthy for the vagina.

When recommending a vaginal moisturizer, Dr. Rowen suggests a pH-balanced gel with hyaluronic acid. Soothing topical agents such as bupivacaine hydrochloride can also be used for vaginal or vulvar pain, and topical anesthetics such as lidocaine may improve symptoms of dyspareunia.

Local estrogen therapy is generally preferred for vaginal dryness/dyspareunia, since its efficacy is targeted to vaginal tissues, with minimal systemic absorption and fewer adverse effects, noted Dr. Rowen. Local estrogen can improve lubrication, increase blood flow, and improve sensation in vaginal tissues; it is available in a cream, tablet, or ring. However, according to Dr. Rowen, prescribers should favor tablets or rings for patients with hormone-sensitive breast cancer, as the cream is inserted into the vagina and can result in higher systemic levels of estrogen. A progestin component is not needed in women with a uterus, she added.

“If someone is having a vaginal symptom, you want to actually put something on the vagina,” explained Dr. Rowen. “The vagina has estrogen receptors, so that’s where you want to be putting the hormone.”

Prasterone (vaginal dehydroepiandrosterone) has been approved by the U.S. Food and Drug Administration (FDA). It has been shown to improve symptoms in women with genitourinary syndrome of menopause without increasing systemic hormone levels, although there are no published data yet on using this drug in women who are receiving aromatase inhibitors.

According to Dr. Rowen, the key takeaway when it comes to choosing candidates for local therapy is that one size does not fit all. She said that no study has looked at the main clinical outcome of concern: breast cancer recurrence (although recurrence has been reported in survivors who used systemic hormone therapy). Many oncologists are comfortable with local estrogen therapy in patients with hormone receptor–positive disease, even with those who are receiving aromatase inhibitors. When prescribing local hormones, however, physicians should always consider the issue of absorption, as it varies by the active ingredient, she advised. Also, if a woman is complaining of vulvar symptoms, treatment should be isolated at the level of the vulva, as it is less vascular than the vagina.

Treating Low Libido

According to Dr. Rowen, vaginal dryness and pain should always be treated before addressing loss of libido. Once pain is addressed, she added, off-label use of antidepressants can be considered as a starting point (bupropion and buspirone), as such agents have shown some efficacy in improving desire.

Flibanserin has improved sexual desire over placebo in clinical trials,³ and it was the first FDA-approved drug for the treatment of low libido in premenopausal women. According to Dr. Rowen, “there is no reason to believe that this drug is going to cause any problems in our patients with cancer, as it doesn’t affect hormones.” It is not yet approved for postmenopausal women, but the evidence seems to show activity, she added.

In June 2019, bremelanotide, a melanocortin 4 receptor agonist, was approved by the FDA for use in premenopausal women. Delivered via auto-injection, this agent has led to improvements in sexual function and an increase in the number of satisfying sexual events women experienced in clinical trials.⁴

“I consider it a problem to use satisfying sexual events as a marker, because what women are complaining to me about is not that they are not having satisfying sex. They’re complaining that they have low desire; the desire for sex is what is most important for women,” noted Dr. Rowen. “The nice thing about bremelanotide is that it is an as-needed medication, versus flibanserin, which is a nightly drug.”

Unfortunately, there is still no FDA-approved treatment for postmenopausal women, but the strongest data support the use of off-label testosterone, Dr. Rowen noted.

Any woman who will receive radiation to the pelvis should be counseled on the use of dilators to effectively manage vaginal stenosis, suggested Dr. Rowen. “I see patients before radiation to conduct an exam and explain what radiation will do to the vaginal tissue,” she added. “I teach them about dilator therapy, with a follow-up exam scheduled 4 to 6 weeks after completion of radiation.”

According to Dr. Rowen, “Many oncologists and radiation oncologists know that this is important, but they often don’t have time to talk about it. This is where partnering with a colleague more familiar with the vagina and vulva, especially a gynecologist, plays a big role.”

She also noted that elaboration of a therapeutic plan should take into account the physical as well as emotional aspects of sexuality. It should consider how to redefine sex for a cancer survivor. “Some of these women are not going to be able to have intercourse,” stated Dr. Rowen. “This focus on intercourse is a huge problem in general, and there are many others ways for people to be intimate.” ■

DISCLOSURE: Drs. Mulhall and Rowen reported no conflicts of interest.

REFERENCES

1. Mulhall J, Rowen T: Sexual Health: Treatment Strategies. 2019 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology International Symposium on Supportive Care in Cancer. Plenary Session 3. Presented June 23, 2019.

2. Moreira ED Jr, Brock G, Glasser DB, et al: Help‐seeking behaviour for sexual problems: The Global Study of Sexual Attitudes and Behaviors. Int J Clin Pract 59:6-16, 2005.

3. Katz M, DeRogatis LR, Ackerman R, et al: Efficacy of flibanserin in women with hypoactive sexual desire disorder: Results from the BEGONIA trial. J Sex Med 10:1807-1815, 2013.

4. Clayton AH, Althof SE, Kingsberg S, et al: Bremelanotide for female sexual dysfunctions in premenopausal women: A randomized, placebo-controlled dose-finding trial. Womens Health (Lond) 12:325-337, 2016.