Transdermal Patch         

Hormonal contraception is available via transdermal patches that combine estrogen and progestin. It is currently available as ethinyl estradiol 35mcg per day and norelgestromin 150mcg per day and levonorgestrel 120mcg per day and ethinyl estradiol 30mcg per day. Contraceptive efficacy for both patches is comparable to oral contraceptives.⁶⁰ EE/norelgestromin has a pregnancy rate of 1.07 (95% CI 0.6 – 1.76)  per 100 woman-years, while EE/LNG patch had a 3.5% (95% CI 1.8-5.2) pregnancy rate per 100 woman-years.^62,63

The EE/norelgestromin patch contains three layers: a water-resistant outer layer, a middle medication, and adhesive layer, and an inner layer that functions as a release liner.⁶⁴ The EE/LNG patch has five layers, with the two innermost layers containing the active ingredients. The EE/LNG patch is twice as large as the EE/norelgestromin patch, 14cm² vs. 28cm².

The total EE exposure is approximately 60% higher than comparable COCs of a similar dosage strength; however, the peak EE concentrations are about 25% lower. The total AUC of the EE/norelgestromin patch is comparable to 50 mcg of oral EE. The pharmacokinetics data is based on weeks one and three of the first two usage cycles. The clinical significance of these findings is not clear.^65,66

Patches offer the advantage of increased adherence because of the infrequency of application compared to oral contraceptives. In a clinical trial, 88% of the contraceptive cycles had perfect compliance with the patch, while only 78% of the oral contraceptive cycles had perfect compliance.⁶⁷ Transdermal products offer a more stable plasma level of hormones as delivery to the bloodstream is constant while the patch is used. Continuous application is possible to prevent a return to menses.

The patch is not recommended for those with a BMI of 30 or above or who weigh more than 90kg due to decreased absorption and inadequate contraceptive ability. The patch can detach prematurely, resulting in pregnancy if not promptly reapplied.

Application site adverse reactions include redness, itching, and allergic reactions. The EE/LNG and EE/norelgestromin patches use a different adhesive; therefore, an allergic reaction to one product may not occur with the other. The rate of skin reactions is 17% in EE/norelgestromin users vs. 3% in EE/LNG users.^63,64* Irregular bleeding and spotting can occur with transdermal contraception. In the initial cycle, unscheduled bleeding occurs in up to 18% of EE/norelgestromin users, stabilizing and decreasing to 5% to 7% at approximately six months. Unscheduled bleeding during the initial first two cycles was reported in 50% to 60% of EE/LNG, which drops to 42% by the 13th cycle. The mean number of unscheduled bleeding days was 1.6 by cycle 13. Weight increase occurs in approximately 2.5% of patients.^62,63* A study comparing EE/norelgestromin to EE/LNG triphasic revealed a mean change in body weight by 0.3 kg for both interventions.⁶⁸ The patches appear to have a null effect on existing mood disorders or mood in general. The discontinuation rate for EE/norelgestromin patches is 3%, and EE/LNG patches is 11%.⁶⁹

It is unclear if the patches present a higher risk of VTE as there is conflicting data. A 2017 clinical review examined this and determined that the available evidence did not demonstrate a significantly increased risk of VTE with patches compared to oral contraceptives, and any elevation in risk would be slight at the population level. Many of the trials included had methodological issues such as the use of insurance databases with verification, not adjusting for confounders, the low absolute rate of VTE, and lack of new users in the study, which likely have a higher risk of VTE.⁷⁰

Counseling points revolve around how to apply the patch, what to do if a patch detaches, and how to switch from another contraceptive type. Patients who desire menses should apply one patch once weekly for three weeks each month, followed by a patch-free week. Continuous use is possible if a patient wants to stop menses or control when they have withdrawal bleeding. If there is a delay in administering the first patch of a new cycle, a new patch should be placed as soon as possible, and a backup method of contraception should be used for one week. The day the new patch is applied becomes the new patch change day. If the delay occurs during the second or third patch in a cycle, a 48-hour grace period exists due to the continued release of adequate levels of hormones from the patch. If the patch is changed during the 48-hour window, no backup method is necessary, and the patient can remain on the same patch change schedule. If a delay of more than 48 hours occurs, the day the new patch is placed is now the new patch change day, and the patient needs to use barrier contraception or abstinence for seven days to prevent unwanted pregnancy. Retaining the third patch past its removal time carries less risk if the patient is on a non-continuous cycle. The patient should remove the patch when they remember and start the 1st patch of the new cycle on their usual change day.^63,64*

The patch can be started at any time; however, if it is initiated more than five days after the start of menses, a barrier method of contraception or abstinence is recommended for seven days. The patch can be applied to the lower abdomen, buttocks, or upper body (but not the breasts) and should be rotated to a new application site with each application. The patient is instructed to apply the patch on the same day each week. Daily activities such as bathing, swimming, or exercise do not affect skin adherence. Heat and humidity do not increase the risk of detachment. If the patch detaches less than 24 hours has passed, the patient can reapply the patch to the same place or replace it with a new patch. If a patch separates for more than 24 hours, start a new cycle with a new patch and use a backup method of contraception for one week. If the patch has lost its adhesiveness, a new patch should be used. Instruct patients not to apply tape or bandages over the patch to maintain it in place.

When switching from an oral contraceptive vaginal ring or a different patch type, advise the patient to complete their existing cycle and start the patch on the first day of the next cycle and discontinue their old therapy. A barrier method or abstinence is recommended if more than a week has elapsed between contraceptive doses. Patients switching from DMPA are advised to start the patch when their next injection is due. A patch should be initiated on the first day an IUD or LNG implant is removed. Abstinence or a barrier method of contraception is recommended when switching from DMPA, IUD, or LNG implant, and more than one week has passed since removal.^62,63*

Hormone levels begin to decline within days following the removal of a contraceptive patch. FSH, LH, and estradiol levels return to baseline within six weeks of discontinuing therapy. Attempts to conceive can begin as soon as the patch is discontinued.^64*

Vaginal Ring

Hormonal contraception is available via a temporary ring placed inside the vagina that releases estrogen and progestin. Vaginal rings are a good option for women who desire combined hormonal contraception but do not want to take daily oral medication. Attitude towards the vaginal ring are favorable; 84% to 96% of women report satisfaction with a vaginal ring, and 87 to 98% would recommend vaginal rings to a friend.^71,72 Ring users may be less likely to discontinue therapy compared to COC users.^73,74 Adherence to recommended use occurs in 80% to 90% of users.^75,76

There are two rings available that differ in the type of progestin present. One contains etonogestrel (120 mcg per day) and ethinyl estradiol (15 mcg per day), the other includes segesterone acetate (150 mcg per day) and ethinyl estradiol (13 mcg per day). The etonogestrel/EE ring is 54 mm in diameter and 4 mm in cross-sectional area. It is inserted in the vaginal canal by the patient, left in place for three weeks, and then removed for one week to allow menses. The device is latex-free.⁷⁷ The amount of EE released with the ring is lower than that of COCs. Compared to a COC containing 30 mcg, the EE/etonogestrel ring reduced systemic exposure to EE by approximately 50%.⁷⁸ Another study compared 30 mcg per COC with 20 mcg per day in patch form and 15 mcg per day in ring form. The systemic exposure was 3.4 times lower for ring users than patch users and 2.1 times lower than COC users.^65* The peak concentration is achieved within the first seven days after insertion. The etonogestrel/EE ring must be refrigerated to be effective. Overall efficacy is comparable to oral COCs, with one study finding a 99.1% efficacy rate in preventing unwanted pregnancy. Half of the 22 pregnancies in the study were attributable to compliance issues.⁷⁹

The segesterone/EE ring is a slightly larger one-year reusable ring than the etonogestrel/EE ring at 56 mm in diameter and 8.4mm in cross-sectional area. The ring follows the same three weeks, one-week pattern but can be reused for 13 cycles before needing to be discarded. Hormone levels peak after two hours and then level at approximately 96 hours post-insertion. The segesterone/EE ring does not have to be refrigerated. The unintended pregnancy rate is 2.98 per 100 women-years.⁸⁰

There is no evidence of increased risk of breakthrough pregnancy or VTE in obese women who use vaginal rings. Systemic side effects are the same as other types of combined hormonal contraceptives. Local side effects include vaginitis, (OR 2.48 to 2.84), vaginal wetness, and leukorrhea (OR 3.21 to 6.42). There is no increased risk of vaginal or cervical infections from ring use.^61* Unscheduled bleeding or spotting may occur. A study examining continuous ring use noted a median of zero bleeding days and ten spotting days in the first three months compared to 7.5 bleeding and eight spotting days for a 28-day cycle ring.⁸¹ Alterations in mood were no more likely with the etonogestrel/EE ring than COCs.^61* The incidence of thromboembolic events is not higher for ring users when compared to other types of CHCs.^82,83 Case reports of toxic shock syndrome exist, but it is not known if the ring was the causative factor.

When the patient inserts the ring, a comfortable position should be chosen. Instruct the patient to press the sides of the ring together and place the ring as high as possible in the vagina as tolerable to prevent the ring from accidentally dislodging. The vaginal ring should not be removed during intercourse as this may compromise efficacy. Once removed, the segesterone/EE ring should be washed with soap and water, dried with a clean cloth, and stored in its case. The initiation and discard dates can be written on the case. Women should be advised to check to ensure the ring is periodically in the proper position.

Delays in ring removal can occur. If the ring has been in place for more than three but less than or equal to five weeks, the ring should be removed. A new ring (etonogestrel/EE) or a clean ring (segesterone/EE) should be inserted after a one-week ring-free interval. A new ring can be inserted immediately for continuous application, but breakthrough bleeding may occur. For etonogestrel/EE rings left in place longer than five weeks, the old ring should be removed, and a new ring inserted. Abstinence or barrier contraception is required for seven days to prevent pregnancy.

Suppose there is a delay in inserting a new ring (etonogestrel/EE) or current ring (segesterone/EE)  by less than 48 hours. In that case, the ring should be reinserted as soon as possible and removed again at the regular removal date without the need for backup contraception. Delays of greater than 48 hours require a backup method of contraception; the new removal date is based upon this insertion date.

Continuous use with either ring is possible; however, there is no available data for segesterone/EE. If the ring breaks, it will not reduce contraceptive efficacy but increases the risk of unintended removal. The broken ring should be replaced when a new ring is available for insertion. If the etonogestrel/EE ring is accidentally expelled and less than three hours have passed, the ring may be reinserted after cleaning without backup contraception. If more than three hours have passed and it is the first two weeks of the cycle, a backup contraception method is needed until the ring has been in place for seven days. If this happens during week three, the woman can either insert a new ring and begin a new two-week cycle while using abstinence or barrier contraception until the new ring has been in place for seven days or leave the ring out for seven days to initiate the ring free period and begin menses. A new ring should be inserted after seven days, and a backup contraception method is recommended until the new ring has been in place for seven days. If the duration is unknown and the woman has been sexually active, pregnancy should be ruled out before reinserting the ring.

If the segesterone/EE ring is expelled for less than two hours, it can be reused after cleaning without the need for backup contraception. After two or more hours, a backup contraceptive method is necessary for seven days. Return to fertility occurs with a median time of ovulation at 19 days post removal of the etonogestrel/EE ring.⁸⁴ All 290 women in the initial trials of segesterone/EE resumed menses within six months of discontinuation.^80* Female barrier products such as the diaphragm, cervical cap, or female condom should not be used with the vaginal rings because they can interfere with a barrier method’s effectiveness. Oil-based lubricants are not compatible with the rings, but water-based lubricants are. Tampons can safely be used during menses as the rings are usually not in place during that time frame.