MenoPatch: Advancing Transdermal Hormone Replacement Therapy for Menopausal Symptom Management

Purpose: Menopause typically spans the ages of 45 to 55 in women as the menstrual cycle ceases following the physiological decrease in circulating estrogen. This transition unfolds gradually, with various symptomatic manifestations experienced even during the perimenopausal period prior to menopause. Common symptoms include night sweats, mood swings, fatigue, and sleep disturbances. However, both perimenopausal and menopausal symptoms remain largely neglected and untreated despite its substantial implications on a woman’s health and daily experience. In fact, around 80% of women encounter one or more menopausal symptoms, however only 10% actively seek relief (Doamekpor et al.). Hormone replacement therapy (HRT), typically combining estrogen and a progestin, provides symptomatic relief and mitigates the risk of diabetes, osteopenia, and cardiovascular ailments. HRT is most commonly administered via oral and transdermal routes. However, orally administered estrogen carries an elevated risk of venous thromboembolism (VTE), while transdermal patches offer limited dosage options. Currently, only two commercially available patches deliver both estrogen and progestin at fixed doses. If these patches and their doses are not suitable for a patient, they must resort to an estrogen patch supplemented with an oral progestin. Existing estradiol patches offer limited dosing options and need to be replaced once or twice a week. The hallmark feature of MenoPatch is its ability to deliver customizable doses of estrogen and progestin through the innovative port system. This provides clinicians the flexibility to increase hormone concentrations to meet each patient’s unique needs without requiring patch removal, ensuring precise symptom management and less time to identify a patient’s dosing needs. The patch contains an advanced release mechanism that delivers hormones consistently and in a controlled manner throughout its wear time, reducing fluctuations in hormone levels and minimizing side effects seen with traditional treatments. Additionally, MenoPatch aspires to offer extended wear with monthly applications, simplifying treatment schedules and decreasing frequent interventions. Accordingly, we are developing a transdermal patch that allows customizable dosing to provide a convenient method to administer HRT for symptomatic relief during menopause. Methods: MenoPatch is an innovative transdermal patch, engineered for effective management of the spectrum of menopausal symptoms via tailored dosage and sustained administration. MenoPatch is a modified reservoir style patch with two innovative elements: (1) a 3D-printed reservoir with a rubber septum through which customized additions of hormone can be added via needle-less syringe, and (2) a proprietary hydrogel imbedded in the reservoir to allow steady hormone administration over the course of four weeks. A commercially available rate-controlled release membrane seals the hydrogel within the reservoir. Made from thermoplastic polyurethane (TPU 88A), the 3D-printed reservoir designs (diameters of 2 inch, 1 inch, or 0.5 inch) provide sturdy containment, protecting the hydrogel solution. We synthesized several versions of an alginate-polyacrylamide hydrogel to allow sustained hormone release for a prolonged therapeutic effect. Once 100-200 mg of dehydrated hydrogel was fixed into the reservoir, the underside of the reservoir was sealed with a rate-controlled release membrane (CoTran 9716, 3M) using Permatex 80050 silicon glue. The glue was allowed to dry for 24 hours before using a needle-less syringe to load the patch with a hormone formulation (17β-estradiol at 10 mg/mL in 70% ethanol). To test in-vitro hormone elution from the patch, we employed g Franz diffusion cell studies (300 mL volume, PermeGear) with an acceptor solution of 1xPBS pH 7.2 with 5% ethanol. Enzyme-linked immunosorbent assay (ELISA, Abcam) measurements were then used to measure the concentrations of hormone that eluted from the patch and into the acceptor solution. Results: The devised transdermal patch integrates key components including a reservoir containing a dehydrated hydrogel, a dual-release mechanism comprising the hydrogel and a rate-controlling release membrane, and a port enabling customizable hormone delivery. A novel port and reservoir was developed for the drug delivery system, while utilizing readily available commercial materials for the rate-controlling membrane. In vitro studies using a Franz diffusion cell demonstrated the patch’s capacity to effectively release hormones. ELISA analyses of samples collected from the diffusion cell confirmed the presence of eluted hormones. After loading the prototype patch with 15 mg 17β-estradiol, the Franz diffusion experiments were conducted in an incubator set at 32°C, resulting in the elution of 0.16 mg estradiol into the acceptor solution at 22 hours. By 71 hours, 2.9 mg estradiol had eluted into the acceptor solution. These initial experiments did not incorporate hydrogel into the patch. Conclusions: We have been able to successfully build and test a prototype transdermal patch that can be loaded with customized amounts of 17β-estradiol through a needle-less port system. Work is ongoing to incorporate a novel hydrogel to allow steady rates of hormone elution over several weeks.