The ‘conditioning’ hypothesis of Rowland and Motofei separates the physiological ejaculatory processes into “hardwired” (unchangeable) and “softwired” (amenable to modulation) central and peripheral networks. Although these “hard-wired” components might respond in a graded manner to external modulators, they themselves are not the primary source of the modulation. While it seems likely that men cannot willfully and directly change underlying neurobiological responses (e.g., receptor sensitivity, inhibitory postsynaptic potentials, neurotransmitter release, etc.) in order to affect their orgasmic response, intentional modification of arousal, libido or motivation may alter the triggers for ejaculation. This view argues that treatment of PE aimed at multiple levels of functioning will be self-enhancing and ultimately more effective in producing positive therapeutic outcomes than strategies relying solely on either psychological or biological approaches [32].

Sunay assessed acupuncture for PE (IELT <2 min) compared to daily paroxetine and sham acupuncture. Ninety men with PE received either 20 mg of daily paroxetine, twice weekly acupuncture (with points chosen based on standard acupuncture practice), or twice weekly sham acupuncture (placement of a needle at the same point as the treatment group without skin penetration to produce a “pricking” sensation) for 4 weeks (n = 30 each arm). Men with primary PE made up about 2/3rds of the study cohort and were evenly distributed between treatment arms. IELT was measured for each individual man and mean rank IELT was determined. Paroxetine produced the longest mean-rank increase in IELT at 83 s compared to 66 s in the acupuncture arm and 33 s in the sham arm. The difference between both paroxetine and acupuncture arms was significantly greater than what was observed in the control arm [40]. This manuscript is limited in that men with both secondary and primary PE were enrolled. However, these data suggest that acupuncture may exert an effect on IELT but this effect appears to be less than what is observed with medical therapy. Further investigations of this modality may be warranted.

Herbal therapies are an increasingly popular treatment for a variety of health concerns, including issues pertaining to sexuality [41]. These treatments may be preferred by individuals who cannot afford prescription medications, individuals who prefer a naturopathic approach to health, and individuals who are mistrustful of prescribed pharmaceuticals. Herbals and nutraceuticals are not regulated by the FDA or other international regulatory agencies and there has been substantial concern about irregularities (contamination, counterfeiting, intentional or accidental mislabeling) of over -the-counter herbal drugs [41]. Nevertheless, these compounds may in some cases have utility in the management of sexual concerns including PE.

Satureja montana (winter savory) is a medicinal plant traditionally used to treat disorders including male sexual dysfunction. Zavattia et al. evaluated the effect of the plant’s hydroalcoholic extract, given acutely and subacutely, on copulatory behavior of sexually potent male rats. Groups of 5–7 animals were given 0 mg, 25 or 50 mg/kg of the extract acutely (testing 45 min post-dose) and subacutely (testing after eight once daily treatments) for: mount latency; intromission latency; ejaculation latency; postejaculatory interval; mount frequency; intromission frequency. Acute administration of Satureja montana extract significantly increased ejaculation latency and reduced the number of intromissions before ejaculation without affecting the percentage of animals achieving ejaculation (100 % in all experimental groups) [42]. While the results are interesting it is not clear that these findings are applicable to the human condition of PE; further human studies are required. Gu-jing-mai-si-ha is an herbal compound consisting of Radix anacycli pyrethri, Mastiche, Fructus Cardamomi, Rhizoma Cyperi, Stigma Croci, Semen Myristicae, Radix Curcumae, Folium Syringae oblatae, Radix et Rhizoma Nardostachyos, Fructus Tsaoko, and Flos Rosae rugosae. It has been hypothesized that this decoction may treat PE by modulation of smooth muscle necessary for ejaculation. Song investigated the effect of gu-jing-mai-si-ha tablets (administered as 4 tablets of unspecified dose twice daily for 15 days) for treatment of primary and secondary PE (IELT <2 min, no specifics on how many primary vs. secondary) in a randomized prospective trial of 69 patients. A comparison group of patients who were not treated with any intervention was included. Evaluation of response was conducted at baseline and “at the end of the treatment period” although it is not clarified if this was on the day of the last dose. Mean IELT improved from 1.27 to 2.73 min in the treatment group compared to a change of mean IELT from 1.25 to 1.16 min in the untreated group. Serum level of NO and PGF2α increased significantly in the treated group; the authors speculate that this effect may be responsible for the change in IELT [43]. Limitations of this study include unclear enrollment criteria and clinical endpoints, lack of a true placebo control group, unclear means of calculating IELT, and difficulty in determination of the active moiety of this complex herbal extract.

It has been speculated that enhanced sensitivity of the glans penis may account for some cases of PE [44]. Indeed, modulation of penile sensitivity is the underlying principle for topical anesthetics in the management of PE [6, 8]. While reversible modulation of penile sensitivity is within the bounds of standard of care, some authors have investigated surgical approaches to permanently decrease glanular sensitivity and in so doing prolong ejaculatory latency.