S1’s first two drug candidates Lorexys™ and S1P-205, are for sexual desire problems. Yet that doesn’t mean S1 fails to address problems with sexual arousal or orgasm.

First, let’s consider the functional sexual cycle. For men and women alike, sexual desire normally stimulates sexual arousal; sexual arousal leads to orgasm; and orgasm leads to resolution (feelings of satisfaction). So, it makes sense that impairment of one phase would lead to dysfunction of subsequent phases, i.e., that loss of desire would keep a man or woman from getting aroused, that a lack of arousal would prevent orgasm; and that lack of orgasm would lead to a lack of resolution. Thus, treating desire problems might help some arousal problems, if they flow from a lack of desire. So, S1’s studies of Lorexys™ for desire problems of women will include measurement of arousal and orgasm problems, and their possible resolution with Lorexys™. We plan similar to use similar measures for men in our first studies of S1P-205, in which the components of Lorexys™ are specially formulated for men’s needs.

However, Women’s sexual arousal and orgasm problems can occur though desire remains intact. The broadest population-based surveys [e.g., Shifren 2008] have shown considerable overlap yet frequent separation between those with distressing dysfunction in desire, arousal, and orgasm, depending on a woman’s age.

Such disorders, and overlap of such disorders, are especially prevalent in older women. The PRESIDE study of US women of all ages is the most authoritative such survey, with a sample of over 30,000, about twenty times larger than any other population survey. In PRESIDE, the frequency of overlap of dysfunction in the three phases of sexual function was much lower in women 18-44 years of age than in older women. 27% of women ages 18-44 reported any dysfunction of desire, arousal, and/or orgasm, while the rates for low arousal and low orgasm were 10% each. 45% of women age 45-64 reported any of the three dysfunctions, with rates for each of the low arousal or low orgasm of 17 and 24%. In women 65 or older, any sexual dysfunctional was reported by 80%, and low arousal or 65 and 55%, showing a very high rate of arousal and orgasm problems, and a very high overlap between such problems and desire problems. Figure 1 below shows this (taken from Shifren 2008, Table 2).

The main differences among age groups were that postmenopausal women tend to have lower levels of sexual distress yet were much more likely to have difficulties with desire, arousal, and orgasm.

Skeptics have discounted such incidence values as inflated. As noted above, PRESIDE was unique in asking not only about sexual problems but also about sexual distress, depression, and antidepressant use (a frequent cause of sexual dysfunction). PRESIDE found that about a quarter of the women with a sexual problem had considerable distress about it and neither depression nor an antidepressant to blame as the cause–that the incidence of sexual arousal disorder with marked sexual distress was about 6%, and that of female orgasmic disorder was about 5% overall. For arousal and orgasm problems alike, twice as many women age 45 or older were affected (6-7%) as women 44 or younger (3%). (Shifren 2008).

In other studies, that 45-year cutoff for a high incidence of sexual problems in the PRESIDE study was found to be the average onset of peri-menopause (the onset of irregularity of menstrual cycles; Huang, 2011). Entry into the peri-menopause is characterized by increasing levels of follicle-stimulating hormone and increasing variability in menstrual cycle length. (The late menopausal transition is characterized by the occurrence of skipped cycles or amenorrhea).

Some natural products of the body stimulate sexual arousal and/or orgasm without necessarily quickening desire. The published literature shows potential therapeutic application of the active component of S1B-307, a natural peptide (chain of amino acids) for treating women’s sexual disorders of arousal and/or orgasm. This could be of benefit to younger or older women, though older women are much more likely to have arousal or orgasm problems than younger women.

S1 has more in store to help women, too. S1’s drug candidate S1B-3006 will combine elements of S1B-307 and Lorexys™ in order to help women who have even more severe sexual problems—disorders of desire, arousal, and/or orgasm that are resistant to our other agents or are due to debilitating medical illness.

Men haven’t been studied as much as women, but it’s already clear that age is not as much of a factor, that men have more kinds of sexual problems, and that erectile dysfunction is not the most frequent male sexual problem. Not according to each of the three large population-representative surveys of English-speaking men—one in the US, one in the UK, and one in Australia.

The US population-representative study was one in which over 1200 men age 18-59 were surveyed (Figure 2). Symptoms were endorsed by men as a “critical symptom or problem during the past twelve months.” Lacking interest in sex, premature ejaculation, and performance anxiety were each more common than what ED (trouble maintaining or achieving an erection). Unable to climax was about half as frequent as ED.

FIGURE 2. % of US Men with Sexual Dysfunction in the National Health and Social Life Survey*

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*n’s = 1243-1249 per item answered; values for men in their twenties were about the same as for men in their thirties. Laumann, 1999

This survey was performed by experts in the field and met contemporary standards for population-representative surveys but has been criticized by some therapists as exaggerated. The % values in Figure 2 might be discounted by one-half to 2/3 to exclude those without sexual distress (Fugl-Meyer 2002; Hayes 2006). (Depression and antidepressants are much less of a factor for men than for women; only about half as many men as women get depressed or use an antidepressant). Still, male sexual difficulties like HSDD must be roughly as frequent as ED, and orgasmic disorder about half as prevalent as ED. The number of affected men in the US with HSDD alone must be at least 5-7%, about 5-7 million men. Besides, who’s to say that, if a guy complains of low sexual desire or inability to climax to a doctor that he must prove sexual distress before he should be prescribed a treatment for it? No such proof is required for ED.

Of course, high prevalences of male sexual problems are not unique to the US. The UK survey (Mercer, 2003) asked almost 4000 men about sexual problems lasting at least a month, and about those lasting at least six months, in the past year. The prevalences for at least one month of three problems were about the same as in the US survey: lack of interest in sex (17%); unable to achieve orgasm (5%); and trouble with erections (6%). The prevalences for at least six months of each problem were much lower, but still confirmed that lack of sexual desire, anxiety about performance, and premature ejaculation were problematic for more men than ED. The Australian survey [Najman 2003], in 876 men, showed similar prevalences.

Still, ED might be seen as the main sexual problem of men, because ED is the irreducible male sexual difficulty: control of erections is tightly bound to sexual desire, so loss of interest in sex begets ED. So does performance anxiety. And what’s the point of keeping an erection if a man can’t have a climax? But that does not mean a drug for ED is usually sufficient. ED drugs fail in about 50% to 60% of men according to one of the foremost experts in field, urologist Stanley Althof [Althof 2002] and failed in almost half of the attempts at sexual intercourse in the late-stage efficacy studies of sildenafil, though the drug demonstrated statistically significant improvement compared to placebo in all 21 studies [Viagra package insert 2012].

Clearly, men need more help for sexual problems. So S1 plans to develop S1B-307 for ED that won’t respond to the currently available drugs, and for male orgasm problems; to develop S1P-205 for male HSDD; and to follow on with S1B-3006 for men with multiple and difficult-to-treat sexual dysfunctions.