Hormonal intravaginal rings could facilitate combination therapies for several conditions


“Topical drug delivery also provides higher concentrations of the drug to the target site and has fewer side effects,” wrote the authors.

Hormonal intravaginal rings (IVR), which are minimally invasive polymeric devices designed for the sustained and prolonged release of different drugs such as hormones, might facilitate combination therapies for endometriosis, estrogen deficiency, and urogenital atrophy by administering multiple drugs in a single IVR, while eliminating the side effects of conventional drug-delivery methods.

IVRs also can be used for contraception and could substantially improve women's quality of life worldwide in a short period of time.

These are some of the findings of a literature review in Geburtshilfe und Frauenheilkunde, the journal of the German Society of Gynecology and Obstetrics.

Another benefit of using topical drug delivery systems like IVRs is that systemic drug delivery may cause drug resistance, due to elevated drug levels.

“Topical drug delivery also provides higher concentrations of the drug to the target site and has fewer side effects,” wrote the authors.

Moreover, by delivering a drug vaginally, the hepatic first-pass effect is avoided, thus resulting in higher absorption.

A comprehensive search of publications in MEDLINE/PubMed and of commercial product data on IVRs was conducted to classify and compare various designs of commercially available and non-commercial hormonal IVRs.

The authors found that most hormonal IVRs administer female sex hormones, such as estrogen and progestogens.

IVRs are divided into 3 main material groups: silicone, polyurethane and ethylene-vinyl acetate copolymers (EVA).

Due to their biocompatibility and low toxicity, silicones are commonly used in manufacturing medical products that come into direct contact with the human body, according to the authors.

Likewise, because of its segmented polymeric structure, range of physical properties and good biocompatibility, polyurethane is found in many biomedical devices, including catheters, pacemakers, wound dressings, and drug implants.

EVA has rate-controlling properties. The final result is a rubbery and more permeable polymer, which allows drugs to be released more rapidly from the substrate. The solubility and diffusion coefficient of each drug through the EVA polymeric chain also can be tailored by changing the amount of vinyl acetate.

The molecular weight of polyurethane is lower than silicone or EVA. But for recycling, EVA and polyurethane are more environmentally friendly than silicone.

There are 4 major designs for IVRs that strongly impact their performance and the timing and rate of hormone release: matrix (homogeneous dispersion), reservoir, insert and hybrid (a combination of matrix and reservoir).

A multi-drug insoluble matrix IVR can be segmented or continuous. A segmented multi-drug IVR controls the release rate of each segment individually versus a multi-drug IVR.

With a core reservoir IVR, the release of drugs occurs in zero order and its release characteristics can be easily modified.

An insert IVR can be used as either a single- or multi-drug delivery system by inserting different tablets or drug-loaded vaginal rods into a single IVR that contain several small drug-containing sectors, called pods. Compared to a matrix IVR, a pod IVR can provide sustained drug release over longer periods. The pod design also eliminates the initial burst release.

A hybrid IVR has been proposed using a core embedded in a hot-melt extruded polymer containing the active agent or using an insert-matrix IVR consisting of a medicated polymeric body with cavities for inserting vaginal rods, tablets or pods.

Among the advantages of contraceptive IVRs over other conventional contraceptive methods are convenience, fewer premenstrual symptoms, lighter and more regular menstrual cycles, and reducing the risk of certain cancers like breast cancer due to the lower hormone dose.

The review cites 5 major challenges in developing hormonal IVRs: reduction of burst release, long-term drug delivery, sustained bioavailability, maximizing efficacy, and lowering production costs.

Three possible solutions for reducing burst release are additional membranes, modifying membrane thickness, and releasing a drug at a prearranged time.

Long-term drug delivery might be enhanced by osmotically driven pumps, matrices with controllable swelling, lowering the diffusion rate, using a water-repellent surface to lower the erosion rate, incorporating non-uniform drug-loading profiles and employing multilayered matrices.

Sustained bioavailability might be achieved by changing the drug release rate when confronting different stimuli, whereas maximizing efficacy is possible through using selective hormone receptors, microbicides and the appropriate polymer for the required active pharmaceutical ingredient (API).

Lastly, low-cost techniques and low-cost materials like bio-based polymers would lower production costs.



  1. Rafiei F, Tabesh H, Farzard S, et al. Development of hormonal intravaginal rings: technology and challenges. Geburtshilfe Frauenheilkd. 2021 Jul;81(7):789-806. doi:10.1055/a-1369-9395
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