How often do you talk to female patients about sexual function? What if you don't count discussions of pregnancy, contraception, and sexually transmitted infections?
If you're like many other doctors, the answer may be not so often. “For internists in general, it's not on their radar to think about sexual health concerns,” said Stephanie S. Faubion, MD, MBA, FACP, professor of medicine at the Mayo Clinic in Rochester, Minn., and medical director of the North American Menopause Society.
However, internists should recognize that sexual health equates to overall health and should ask their patients about it, said Lisa Larkin, MD, FACP, a practicing women's health internist in Cincinnati and founder of Ms.Medicine, a national women's health startup company. “If the only thing we can get internists to do is ask one question to identify sexual dysfunction and refer a patient, that would be a home run,” she said.
In a study of about 3,000 U.S. men and women ages 57 to 85 years, about 50% reported having at least one bothersome sexual problem, yet only 38% of men and 22% of women said they had discussed sex with a physician after turning 50, according to results published in August 2007 by the New England Journal of Medicine. “Men are more likely to bring up the problem. They're also more likely to have a doctor ask about the problem, and they're more likely to get a treatment,” said lead author Stacy Tessler Lindau, MD, MAPP, a professor in the departments of obstetrics and gynecology and medicine (geriatrics) at the University of Chicago.
But now, with two new FDA-approved medications to treat sexual dysfunction in women, more patients may be emboldened to ask questions, she said. “With FDA approval of drugs to treat female sexual function problems, we ignite a public conversation on these topics. We raise awareness among doctors and people that these are legitimate health issues, and therefore they're more likely to be discussed and hopefully addressed,” Dr. Lindau said.
While women's health experts don't expect internists to jump headfirst into prescribing these new treatments for sexual dysfunction, they have a simple request: Ask the question, and refer if needed.
Female sexual dysfunction is a relatively prevalent condition across the life course. The term includes conditions characterized by a patient's distress in one or more of the following: desire, arousal, orgasm, and pain, according to the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5). The three main disorders defined by the DSM-5 are genito-pelvic pain/penetration disorder (e.g., penetration difficulty, anxiety, or fear about penetration), interest/arousal disorder (e.g., reduced interest, excitement, and genital sensations), and orgasm disorder (e.g., delay, absence, infrequent, lower intensity).
In a study of more than 31,500 adult women of all ages in the U.S., the estimated prevalence of any self-reported sexual problem (e.g., desire, arousal, orgasm) was about 44%, and the most common sexual problem was low desire, according to results published in the November 2008 Obstetrics & Gynecology. “For about 10% of these women, the problem was associated with distress. That's the population we need to target for treatment,” said Dr. Faubion.
Recent FDA approvals of flibanserin (Addyi) in August 2015 and bremelanotide (Vyleesi) in June were for the same indication: generalized hypoactive sexual desire disorder in premenopausal women. Note that there is only a problem if a woman is distressed about her symptoms, said Dr. Lindau, who is also director of WomanLab.org, a platform that educates women about sexual function. “If your libido is low and you don't feel distressed about that, you don't have a problem. You are not dysfunctional,” she said.
There are several ways to screen women for sexual dysfunction. In a process of care published in the May 2019 Mayo Clinic Proceedings, the International Society for the Study of Women's Sexual Health suggests four different approaches: “just ask,” the ubiquity statement screen for sexual problems and concerns, asking in the context of discussing the patient's relationships, and basic assessment of sexual functioning.
A ubiquity question would be something like, “Many of my patients have noticed changes in sexual function with age. Are you having any problems with sexual function?” said Dr. Lindau.
Another option is asking a simple set of questions that can suffice for a basic assessment of sexual functioning, according to the process of care. The first question can be, “Are you currently involved in a relationship?” or “Are you sexually active?” If yes, responses might be, “What sexual concerns do you have?” and “Have your partners included men, women, or both?” If a patient responds with no, simply ask, “Do you have sexual concerns that you would like to discuss or that are interfering with your sexual function?”
The specific approach a physician takes is less important than asking in the first place, said Dr. Larkin. “Put one question that you feel comfortable asking in your review of systems, and do it with every patient,” she said. “Make it very routine because we know it's so common, and we know patients aren't getting it treated.”
Of course, asking about sexual function doesn't mean you have to fix the problem during that visit, said Dr. Faubion. “If you feel comfortable with it, you can always schedule a follow-up appointment to address that problem specifically, and if you don't feel comfortable with it, [there] are a bunch of resources on how to refer and where to refer,” she said. (See sidebar for referral resources.)
Referrals are especially important because sexual dysfunction is often not caused by biology. Medications will not help if the dysfunction is caused by relationship issues or past trauma, noted Dr. Larkin. That's why she has a pelvic floor physical therapist in her office and often refers patients to sex therapists. “I think I keep them busy.”
For physicians who do want to counsel women about sexual dysfunction, women's health specialist Holly L. Thacker, MD, offered a simple analogy to reassure women that it's normal to not want sex all the time. “I describe it like how exercise is for me. … Once I'm exercising, I feel better, like, ‘This is not so bad, maybe I should do this more often,’” she said. “I use that same analogy with intimacy, and a lot of women identify with that and feel normal.”
While Dr. Lindau counsels her patients about the availability of the new medications and discusses their pros and cons, she's not convinced that, for most patients, their costs and risks are outweighed by their benefits. In addition, she said most of her patients do not meet the DSM-5 criteria for this type of dysfunction because they have an underlying health condition that is at least partially contributing to their diminished libido.
“Women generally have good insight to the factors affecting their libido, and my approach is driven heavily by these insights. … Most of my patients want what I want: to identify the root causes of low libido and correct them,” said Dr. Lindau. For example, if the patient's relationship is strained or communication about sex is poor, then libido can also be negatively impacted. However, there is evidence that the problem can be effectively addressed with attention to the relationship and to communication between partners, she said.
Other common, treatable causes of decreased libido in women are stress, chronic pain, and untreated anxiety or depression, said Dr. Lindau. Poor-quality sleep can also be an unrecognized cause of low libido, and sometimes loss of libido can be the first sign of a systemic illness, she said. “These are all modifiable problems that actually make people healthier and their relationships healthier, and improve their libido, and that's why I prefer these solutions before going to a pill or an injection,” said Dr. Lindau.
New treatment options
At the same time, the recent FDA approvals put two more treatment options on the table.
Both of the medications act on neurotransmitters in the brain. Flibanserin essentially increases dopamine (excitatory) and decreases serotonin (inhibitory), although its exact mechanism of action is somewhat unclear, explained Dr. Faubion. Its most common side effects are dizziness, somnolence, nausea, fatigue, insomnia, and dry mouth. On the other hand, bremelanotide impacts the excitatory neurochemical melanocortin, she said. Its most common side effects are nausea and vomiting (about 40% of trial participants), flushing, injection-site reactions, and headache. (Dr. Larkin is a consultant for AMAG Pharmaceuticals, the manufacturer of bremelanotide.)
For flibanserin, there has been some confusion over concomitant alcohol use. The labeling for the 100-mg, once-nightly (and yes, pink) pill initially included a boxed warning and contraindication stating that women must avoid alcohol when taking the drug, due to concerns of severe hypotension and syncope. In April, however, the FDA ordered a labeling change to allow some alcohol use, saying that women should either discontinue drinking alcohol at least two hours before taking the drug at bedtime or skip the dose that evening.
The safety study responsible for the initial alcohol contraindication was in 25 people, 23 of whom were men. “They had them drink the equivalent of half a bottle of wine in 10 minutes in the morning on a nearly empty stomach after they swallowed the pill, and a couple of people became lightheaded or passed out. I don't think that was surprising,” said Dr. Faubion.
Some patients considering flibanserin may be reluctant to change their drinking habits, said Dr. Thacker, professor and director of the Center for Specialized Women's Health at Cleveland Clinic Lerner College of Medicine in Ohio and executive director of the nonprofit Speaking of Women's Health. “I do have some women who refuse. They will not give up alcohol,” she said. “That makes me, of course, worried about alcohol problems, which 20% of people can have.”
With bremelanotide, patients have an on-demand choice. Unlike flibanserin, which is taken daily, bremelanotide is self-injected into the stomach or thigh before anticipated sexual activity and takes effect within 45 minutes. Dosing is limited to once within 24 hours and eight times per month.
The drug became available in September and may be an attractive option for women who don't want to take a daily medication, said Dr. Larkin. “I think the bremelanotide is going to be a much easier sell to women, at least to try it,” she said.
Cost may be a barrier for both drugs, at least at first. Flibanserin has a list price of more than $400 for a pack of 30 tablets, which is about half what it cost about a year prior. Eligible patients with commercial insurance or who pay with cash can try eight weeks' worth of the medication for free, then pay either $25 or a maximum of $99 per month, depending on insurance coverage, and no more than $99 per month if paying with cash. Similarly, for bremelanotide, eligible patients with commercial insurance or who pay with cash can pay nothing for their first prescription, then a maximum copay of $99 per four-pack. For four injections, the initial list price was $899. Patients with Medicare, Medicaid, or any other state/federal health insurance are ineligible for the drugs' savings programs.
While even the experts have virtually no experience with bremelanotide yet, some have prescribed flibanserin, which was approved under a Risk Evaluation and Mitigation Strategy due to the drug's possible interaction with alcohol. Although the potential side effects and high cost of flibanserin are barriers, Dr. Faubion has used it in her practice. “I've had a few women on it who did feel that their sexual function improved,” she said.
In a practice bulletin published in the July 2019 Obstetrics & Gynecology, the American College of Obstetricians and Gynecologists said that based on limited evidence, flibanserin can be considered as a treatment option for hypoactive sexual desire disorder in premenopausal women without depression who are appropriately counseled about the risks of alcohol use during treatment. The bulletin does not make recommendations on bremelanotide, since it was not yet available.
Dr. Thacker has been prescribing flibanserin for three years and had a list of patients geared up for bremelanotide leading up to its market debut (and is prepared to also give prescriptions for ondansetron if patients experience nausea). “Any time you have more options, it's good. … You just have to be able to inform the patients and let them make choices,” she said.
All that being said, most primary care physicians will probably not be prescribing these medications, Dr. Larkin said. “As much as the drugs are going to be easy to be able to talk to patients about and let them try, I'm not sure that all primary care physicians are going to be willing to do that,” she said.