Vyleesi Year-1 Outcomes From Real Users: What Actually Happens After 12 Months

What 12-month data on Vyleesi actually exists

The RECONNECT program ran two identical 24-week randomized, double-blind, placebo-controlled trials in 1,267 premenopausal women with acquired, generalized HSDD; 1,247 were in the safety population [3]. Both trials then offered a 52-week open-label extension with no placebo arm: of 856 women who completed the double-blind phase, 684 enrolled and 272 completed the extension [1].

Use in the trials was intermittent by design rather than daily. Most participants used Vyleesi two to three times a month and no more than once a week, and the median number of injections across the 24-week double-blind phase was 10 [2]. During the trials patients were told not to exceed twelve doses a month [2]; the current label does not recommend more than 8 doses a month [2].

Desire and distress after 24 weeks

Compared with placebo, bremelanotide increased the FSFI desire-domain score by 0.30 points in study 301 and 0.42 points in study 302, an integrated difference of 0.35 points (all P<0.001) [3]. Distress related to low desire, measured on FSDS-DAO item 13, fell by 0.37, 0.29 and 0.33 points respectively (P<0.001, P=0.005, P<0.001) [3]. The trials found no significant difference between groups in the number of satisfying sexual events [3].

Two limits matter for anyone thinking about a year of treatment. The label states that how bremelanotide improves HSDD is unknown, and that the duration of effect after each dose is unknown [2].

What the 52-week extension reported

In the open-label extension, the most common treatment-emergent adverse events considered related to study drug were nausea (40.4%), flushing (20.6%) and headache (12.0%) [1]. Nausea was the only severe treatment-emergent event experienced by more than one participant across both extension studies [1]. The extension also tracked the same two co-primary endpoints, the FSFI desire domain and FSDS-DAO item 13. Without a placebo group, the extension cannot show how much of the change over time was due to Vyleesi [1].

One safety finding came out of this period. A single case of acute hepatitis occurred in a patient who had received 10 doses over one year, with serum transaminases above 40 times the upper limit of normal; another cause was not identified, so a role for Vyleesi could not be excluded, and liver tests returned to normal four months after the drug was stopped [2].

Nausea: the pattern across months

In the pooled placebo-controlled trials, nausea was reported by 40.0% of Vyleesi patients versus 1.3% on placebo [2]. Median onset was within one hour of the dose and it lasted about two hours [2]. Incidence was highest after the first dose, reported in 21% of patients, then declined to about 3% after later doses [2]. Thirteen percent of Vyleesi patients received an anti-nausea medicine, and 8% stopped the trials because of nausea [2].

In a phase 4 single-dose study, 228 healthy women were randomized to 8 mg oral ondansetron or placebo 30 minutes before a 1.75 mg dose. Taking oral ondansetron before a Vyleesi dose did not significantly reduce nausea in that study [2], and the label says pre-treatment with oral ondansetron is not recommended [2]. Treatment with ondansetron after the injection or after nausea begins has not been formally studied [2].

Blood pressure and heart rate with repeated dosing

In clinical studies Vyleesi produced maximal increases of 6 mmHg systolic and 3 mmHg diastolic, peaking 2 to 4 hours after the dose, with a heart-rate reduction of up to 5 beats per minute; values usually returned to baseline within 12 hours [2]. Those are maximal figures, not averages. In a separate open-label ambulatory monitoring study of 127 premenopausal women dosed once daily for 8 days, mean daytime blood pressure rose 1.9 mmHg systolic (95% CI 1.0 to 2.7) and 1.7 mmHg diastolic (95% CI 0.9 to 2.4), with a mean heart-rate decrease of 0.5 beats per minute [2]. No additive blood pressure or heart-rate effect was seen with repeat dosing 24 hours apart for up to 16 days [2].

Vyleesi is contraindicated in women with uncontrolled hypertension or known cardiovascular disease, and the label says it is not recommended for patients at high risk of cardiovascular disease [2].

Skin darkening with longer use

Focal hyperpigmentation, including darkening of the face, gums or breasts, was reported by 1% of patients who received up to 8 doses a month in the placebo-controlled trials, versus no placebo-treated patients [2]. With daily dosing the rate is far higher: 38% of patients developed focal hyperpigmentation after 8 days of daily dosing, and an additional 14% developed new pigmentary changes after 8 more consecutive days [2]. Patients with dark skin were more likely to develop it, and resolution was not confirmed in all patients after Vyleesi was stopped [2]. The label says to consider discontinuing Vyleesi if hyperpigmentation develops, and that more than 8 doses a month is not recommended because more frequent dosing increases this risk and the length of time each month when blood pressure is raised [2].

Stopping in the first year: what the trials recorded

Discontinuation because of adverse reactions was 18% on Vyleesi versus 2% on placebo; the most common reactions leading to discontinuation were nausea (8%), headache (2%), vomiting (1%), flushing (1%) and injection site reactions (1%) [2]. Overall dropout from the double-blind phase was higher still, 40% versus 13% in study 1 and 39% versus 25% in study 2, and the label also reports an exploratory analysis restricted to women who completed 24 weeks and improved from baseline [2]. Serious adverse reactions were reported in 1.1% of Vyleesi patients versus 0.5% of placebo patients [2].

The label also sets a time-based stopping rule: it says to stop Vyleesi after 8 weeks if there is no improvement in symptoms [2].

Pregnancy exposure within the first year of data

Across the clinical program there were 7 pregnancies in more than 1,057 patients treated with Vyleesi for up to 12 months: no major congenital anomalies were reported, with one miscarriage, five full-term live births and one outcome unknown [2]. The label says to discontinue Vyleesi if pregnancy is suspected and to use effective contraception while taking it; in dogs, fetal harm occurred at exposures at least 16 times the maximum recommended dose based on AUC [2]. On October 22, 2026 FDA approved a labeling supplement updating this section of the label and the patient information; that new text was not yet in DailyMed on October 28, 2026 [6].

What the year-one numbers cannot settle

The label states that the duration of effect after a single dose is unknown and that the optimal window for administration has not been fully characterized [2]. The pharmacokinetics are short: after a 1.75 mg subcutaneous dose the mean terminal half-life is about 2.7 hours, with a range of 1.9 to 4.0 hours [2]. Trial populations were mostly White (86%) and Black (12%), with a mean age of 39 and a mean HSDD duration of about 4 years, which limits how far the results generalize [2].

Vyleesi and PT-141 are not the same product

Vyleesi is the FDA-approved bremelanotide product, a 1.75 mg subcutaneous autoinjector approved on June 21, 2019 (NDA 210557) [2][4]. PT-141 sold as a compounded or research-use peptide is not Vyleesi and is not an FDA-approved drug; compounded drugs are not reviewed by FDA for safety, effectiveness or quality before marketing [5]. These outcomes were measured with Vyleesi, not other products sold as PT-141.