Modern aphrodisiacs address hypoactive sexual desire disorder

Sheryl A. Kingsberg

Hypoactive sexual desire disorder is the most common sexual dysfunction in women, with an estimated prevalence rate of 10% in the United States. Defined as a persistent or recurrent absence or deficiency of sexual desire, the condition known as HSDD is characterized by a lack of sexual appetite, erotic thoughts/fantasies or desire to engage in sexual activity. For affected women, this lack of desire is often a source of distress, frustration and grief.

HSDD is considered a biopsychosocial condition, meaning that it is a combination of biological, interpersonal and sociocultural factors. Although only one drug, flibanserin (Addyi, Sprout Pharmaceuticals), is FDA-approved to treat HSDD, various aphrodisiacs have been used since before the ancient Egyptians to stimulate sexual desire and pleasure.

“The search for aphrodisiacs (derived from ‘Aphrodite’) — any plant, mineral or drug that arouses the sexual instinct, induces venereal desire and increases pleasure and performance — has been ongoing since recorded time,” Sheryl A. Kingsberg, PhD, division chief of OB/GYN behavioral medicine at University Hospitals Cleveland Medical Center, told Endocrine Today. “They are classified as those that are to increase desire, potency or pleasure, and are either psychophysiologic (relying on the senses) or meant to be ingested (food, potions, plants and drugs).”

Kingsberg, who presented on this topic at the North American Menopause Society (NAMS) annual meeting in October, spoke to Endocrine Today about the various factors that can contribute to HSDD and how misunderstandings around this condition are similar to those surrounding depression in previous decades.

How is HSDD different from other types of sexual dysfunction in women?

Kingsberg: It’s important to understand the differentiation between sexual activity, the act of engaging in sexual behaviors, vs. the craving or wanting to want. In addition, to meet the criteria for a diagnosis [of HSDD], a woman must be distressed by this loss or absence of desire.

One way to understand HSDD is to recognize how similar our current understanding of HSDD is to the way we viewed depression 30 years ago. It is best understood from a biopsychosocial perspective, with biological factors, psychological factors, interpersonal factors and sociocultural factors all potentially contributing sexual problems. Prior to the development of safe and effective antidepressants, depression was seen as purely psychological and essentially “all in one’s head,” and the treatment would be primarily psychotherapy and “pulling oneself up by the bootstraps.” Once selective serotonin reuptake inhibitors became commonly used treatments, clinicians and our society began to accept depression as a true medical condition that has situational/external triggers and neurochemical triggers/factors, and treatment might also include psychotherapy (cognitive behavioral therapy), pharmacotherapy or a combination. HSDD is similar. Whereas depression has a key feature of anhedonia, HSDD has loss of enjoyment in sexual activity.

What aphrodisiacs have been used in the past and today to help people with lack of sexual desire?

Kingsberg: Over the years, there have been different things that were believed to be helpful, without scientific proof. Lily of the valley has been observed in several studies to ignite a sense of passion in men. Its sweet, delicate fragrance is a unique odor, particularly for its ability to attract mammals to it. In the eighth century B.C., in Roman times, the remora fish was mixed into potions and sold in the “marketo” to induce passion.

Cobra blood was also thought to be useful for this purpose. On one hand, the user can imagine that some part of the animal’s biological fierceness is now literally within them as well, and on the other, it’s thought that ingesting or slaughtering a dangerous animal is in itself a display of bravery and strength.

A popular aphrodisiac in Colombia and other South American countries, leaf-cutter ants are given as a wedding present. The ants, which are high in protein and low in fat, are typically roasted before they are eaten.

There is currently one drug that is FDA-approved to enhance sexual desire. What are the mechanisms and indications of this drug?

Kingsberg: There is only one FDA-approved pharmacologic treatment for HSDD, and it is approved for premenopausal women: flibanserin. It is a multifunctional serotonin agonist and antagonist. Another drug in the pipeline is bremelanotide (Palatin Technologies), a novel cyclic 7-amino acid melanocortin receptor agonist. Two large randomized controlled trials have shown safety and efficacy in premenopausal women with HSDD (over 1,200 women) and a new drug application was submitted with a decision date of March 2019. Bremelanotide is delivered as a subcutaneous pen injection and is an on-demand treatment with onset of effect within 30 to 45 minutes and duration of approximately 12 to 16 hours.

Do you think there will be more FDA-approved medications for HSDD in the future?

Kingsberg: This was my primary objective for giving my lecture — to communicate that women need and want safe and effective treatments. The search for aphrodisiacs has gone on for centuries without tested, evidence-based, safe products. HSDD and women’s needs for safe and effective treatments have been perceived by naysayers as marketing hype from pharmaceutical companies that have been accused of disease-mongering. What I see every day in my practice, and what I know is true from our research on prevalence of female sexual dysfunctions, is that millions of women are suffering from HSDD and are very much wanting safe and effective treatments. However, the irony is that researchers and pharmaceutical companies that are attempting to develop evidence-based treatments and seek FDA approval by conducting large, rigorous randomized controlled trials are often vilified. Women deserve safe and effective treatments, and they are intelligent and empowered to make informed decisions with their health care providers.

Music is also considered an aphrodisiac. What role can music play in helping people with HSDD, and what songs do you recommend?

Kingsberg: Based on historical records, music has been with our species for a very long time — as long as anything else for which we have evidence. Its ubiquity and its antiquity demonstrate its importance to us; no known culture now or in the past is without music. Music represents a dynamic form of emotion, and the conveying of emotion is considered to be the essence of music. Advances in affective neuroscience, as well as new links between neurochemistry and cognition, have made it possible to study emotion in music more rigorously.

As is true for sex, music has been known to stimulate similar mesolimbic reward pathways in the brain. Functional connectivity analyses show music strongly modulates activity in a network of mesolimbic structures involved in reward processing. Responses in the nucleus accumbens, the ventral tegmental area, as well as the hypothalamus and insula, are strongly correlated to an association between dopamine release and nucleus accumbens response to music.

As for my favorite songs? Narrowing down my examples of songs that reflected or induced desire was absolutely the hardest part of developing my talk. I choose “Sexual Healing” by Marvin Gaye because it also sends the message I was trying to convey to 1,300 women’s health clinicians: That sexuality is important to overall health and quality of life, and they are responsible for addressing the sexual health of their female patients — ie, sexual healing. – by Jennifer Byrne

For more information:

Sheryl A. Kingsberg, PhD, can be reached at 11100 Euclid Av., Cleveland, OH 44106; email: Sheryl.Kingsberg@uhhospitals.org.

Disclosure: Kingsberg reports that she is a paid consultant or on a scientific advisory board for AMAG, Dare, Duchesnay, Emotional Brain, Endoceutics, GTx, IVIX, Lupin, Palatin Technologies, Pfizer, Materna, Sprout, Strategic Science Solutions, TherapeuticsMD and Valeant. She also reports that she receives institutional grant support (clinical trial investigator) from Endoceutics and Palatin.

Sheryl A. Kingsberg

Hypoactive sexual desire disorder is the most common sexual dysfunction in women, with an estimated prevalence rate of 10% in the United States. Defined as a persistent or recurrent absence or deficiency of sexual desire, the condition known as HSDD is characterized by a lack of sexual appetite, erotic thoughts/fantasies or desire to engage in sexual activity. For affected women, this lack of desire is often a source of distress, frustration and grief.

HSDD is considered a biopsychosocial condition, meaning that it is a combination of biological, interpersonal and sociocultural factors. Although only one drug, flibanserin (Addyi, Sprout Pharmaceuticals), is FDA-approved to treat HSDD, various aphrodisiacs have been used since before the ancient Egyptians to stimulate sexual desire and pleasure.

“The search for aphrodisiacs (derived from ‘Aphrodite’) — any plant, mineral or drug that arouses the sexual instinct, induces venereal desire and increases pleasure and performance — has been ongoing since recorded time,” Sheryl A. Kingsberg, PhD, division chief of OB/GYN behavioral medicine at University Hospitals Cleveland Medical Center, told Endocrine Today. “They are classified as those that are to increase desire, potency or pleasure, and are either psychophysiologic (relying on the senses) or meant to be ingested (food, potions, plants and drugs).”

Kingsberg, who presented on this topic at the North American Menopause Society (NAMS) annual meeting in October, spoke to Endocrine Today about the various factors that can contribute to HSDD and how misunderstandings around this condition are similar to those surrounding depression in previous decades.

How is HSDD different from other types of sexual dysfunction in women?

Kingsberg: It’s important to understand the differentiation between sexual activity, the act of engaging in sexual behaviors, vs. the craving or wanting to want. In addition, to meet the criteria for a diagnosis [of HSDD], a woman must be distressed by this loss or absence of desire.

One way to understand HSDD is to recognize how similar our current understanding of HSDD is to the way we viewed depression 30 years ago. It is best understood from a biopsychosocial perspective, with biological factors, psychological factors, interpersonal factors and sociocultural factors all potentially contributing sexual problems. Prior to the development of safe and effective antidepressants, depression was seen as purely psychological and essentially “all in one’s head,” and the treatment would be primarily psychotherapy and “pulling oneself up by the bootstraps.” Once selective serotonin reuptake inhibitors became commonly used treatments, clinicians and our society began to accept depression as a true medical condition that has situational/external triggers and neurochemical triggers/factors, and treatment might also include psychotherapy (cognitive behavioral therapy), pharmacotherapy or a combination. HSDD is similar. Whereas depression has a key feature of anhedonia, HSDD has loss of enjoyment in sexual activity.

What aphrodisiacs have been used in the past and today to help people with lack of sexual desire?

Kingsberg: Over the years, there have been different things that were believed to be helpful, without scientific proof. Lily of the valley has been observed in several studies to ignite a sense of passion in men. Its sweet, delicate fragrance is a unique odor, particularly for its ability to attract mammals to it. In the eighth century B.C., in Roman times, the remora fish was mixed into potions and sold in the “marketo” to induce passion.

Cobra blood was also thought to be useful for this purpose. On one hand, the user can imagine that some part of the animal’s biological fierceness is now literally within them as well, and on the other, it’s thought that ingesting or slaughtering a dangerous animal is in itself a display of bravery and strength.

A popular aphrodisiac in Colombia and other South American countries, leaf-cutter ants are given as a wedding present. The ants, which are high in protein and low in fat, are typically roasted before they are eaten.

There is currently one drug that is FDA-approved to enhance sexual desire. What are the mechanisms and indications of this drug?

Kingsberg: There is only one FDA-approved pharmacologic treatment for HSDD, and it is approved for premenopausal women: flibanserin. It is a multifunctional serotonin agonist and antagonist. Another drug in the pipeline is bremelanotide (Palatin Technologies), a novel cyclic 7-amino acid melanocortin receptor agonist. Two large randomized controlled trials have shown safety and efficacy in premenopausal women with HSDD (over 1,200 women) and a new drug application was submitted with a decision date of March 2019. Bremelanotide is delivered as a subcutaneous pen injection and is an on-demand treatment with onset of effect within 30 to 45 minutes and duration of approximately 12 to 16 hours.

Do you think there will be more FDA-approved medications for HSDD in the future?

Kingsberg: This was my primary objective for giving my lecture — to communicate that women need and want safe and effective treatments. The search for aphrodisiacs has gone on for centuries without tested, evidence-based, safe products. HSDD and women’s needs for safe and effective treatments have been perceived by naysayers as marketing hype from pharmaceutical companies that have been accused of disease-mongering. What I see every day in my practice, and what I know is true from our research on prevalence of female sexual dysfunctions, is that millions of women are suffering from HSDD and are very much wanting safe and effective treatments. However, the irony is that researchers and pharmaceutical companies that are attempting to develop evidence-based treatments and seek FDA approval by conducting large, rigorous randomized controlled trials are often vilified. Women deserve safe and effective treatments, and they are intelligent and empowered to make informed decisions with their health care providers.

Music is also considered an aphrodisiac. What role can music play in helping people with HSDD, and what songs do you recommend?

Kingsberg: Based on historical records, music has been with our species for a very long time — as long as anything else for which we have evidence. Its ubiquity and its antiquity demonstrate its importance to us; no known culture now or in the past is without music. Music represents a dynamic form of emotion, and the conveying of emotion is considered to be the essence of music. Advances in affective neuroscience, as well as new links between neurochemistry and cognition, have made it possible to study emotion in music more rigorously.

As is true for sex, music has been known to stimulate similar mesolimbic reward pathways in the brain. Functional connectivity analyses show music strongly modulates activity in a network of mesolimbic structures involved in reward processing. Responses in the nucleus accumbens, the ventral tegmental area, as well as the hypothalamus and insula, are strongly correlated to an association between dopamine release and nucleus accumbens response to music.

As for my favorite songs? Narrowing down my examples of songs that reflected or induced desire was absolutely the hardest part of developing my talk. I choose “Sexual Healing” by Marvin Gaye because it also sends the message I was trying to convey to 1,300 women’s health clinicians: That sexuality is important to overall health and quality of life, and they are responsible for addressing the sexual health of their female patients — ie, sexual healing. – by Jennifer Byrne

For more information:

Sheryl A. Kingsberg, PhD, can be reached at 11100 Euclid Av., Cleveland, OH 44106; email: Sheryl.Kingsberg@uhhospitals.org.

Disclosure: Kingsberg reports that she is a paid consultant or on a scientific advisory board for AMAG, Dare, Duchesnay, Emotional Brain, Endoceutics, GTx, IVIX, Lupin, Palatin Technologies, Pfizer, Materna, Sprout, Strategic Science Solutions, TherapeuticsMD and Valeant. She also reports that she receives institutional grant support (clinical trial investigator) from Endoceutics and Palatin.