One notable revision to the 2024 U.S. MEC recommendations reflected an increased safety concern for hormonal contraceptive use and sickle cell disease. An updated systematic review found that evidence on the safety of hormonal contraceptive use among women with sickle cell disease remains limited [36]. However, there has been increasing evidence and recognition that sickle cell disease is associated with a high risk for both ATE and VTE [37–43]. Approximately 24% of patients with sickle cell disease will have a stroke by age 45 years [43], and 12% will have a VTE by age 40 years [38]. A meta-analysis reported that adults with sickle cell disease had an increased risk for VTE compared with the general population (odds ratio 4.4, 95% CI 2.6–7.5), with much higher estimates among pregnant and postpartum women with sickle cell disease (odds ratio 33.2, 95% CI 9.7–113.4) [42]. In addition, patterns of thromboembolism may be different and more severe among people with sickle cell disease, including higher risk for PE versus DVT than in the general population [42] and high rates of VTE recurrence (13.2% at 1 year and 24.1% at 5 years) [37].

Recommendations for CHC use for women with sickle cell disease were revised from U.S. MEC 2 to U.S. MEC 4, primarily based on accumulating evidence for the high risk for both ATE and VTE associated with sickle cell disease (Table 2). Similarly, DMPA was revised from U.S. MEC 1 to U.S. MEC 2/3, with a clarification that the category should be assessed according to the severity of sickle cell disease and the risk for thrombosis. All other recommendations remained the same, including U.S. MEC 1 for POPs, implant, and LNG-IUD, and U.S. MEC 2 for copper IUD reflecting concern about increased risk for blood loss.

For women with current or history of VTE, there is concern that hormonal contraceptive use might further increase risk for recurrent VTE. However, there are few studies assessing risk for recurrent VTE associated with concurrent use of hormonal contraception and anticoagulant therapy. The available evidence suggests that women using hormonal contraception while receiving anticoagulant therapy are at low or no risk for recurrent VTE [44]. In particular, new data suggests that among women with acute VTE currently receiving therapeutic doses of anticoagulants, the incidence of recurrent VTE was similar among CHC users, progestin-only contraceptive users, and women not using hormonal therapy [45].

Therefore, CHC use for women with current or history of DVT/PE, using a therapeutic dose of anticoagulants, was changed from U.S. MEC 4 to U.S. MEC 3 (Table 3). Recommendations for CHC use for those using a prophylactic dose of anticoagulants or no anticoagulants after DVT/PE remain U.S. MEC 4 for those at higher risk for recurrence and U.S. MEC 3 for those at lower risk for recurrence. Recommendations for DMPA remain U.S. MEC 2 for those on a therapeutic dose of anticoagulants. DMPA use was changed from U.S. MEC 2 to U.S. MEC 3 for those on a prophylactic dose of anticoagulants or no anticoagulants with higher risk for recurrence, reflecting data on increased risk for VTE with DMPA use (Table 2) [20], but remain U.S. MEC 2 for those on a prophylactic dose or no anticoagulants with lower risk for recurrence. All other methods, including progestin-only methods other than DMPA (i.e., implant, POP, and LNG-IUD) and copper IUD, remain U.S. MEC 2 for women with current or history of DVT/PE on anticoagulant therapy (therapeutic or prophylactic dose). A clarification for the recommendations discusses that women using anticoagulant therapy are at risk for gynecologic complications, such as heavy or prolonged bleeding and hemorrhagic ovarian cysts. Copper IUDs might worsen bleeding. However, hormonal contraceptives may prevent or treat this complication; when a contraceptive method is used as a therapy, rather than solely for contraception, the risk/benefit ratio might differ.

There is limited direct evidence on risk for thromboembolism with use of progestin-only methods among women with medical conditions [20]. As with the general population, DMPA was associated with increased risk for VTE among those with thrombogenic conditions, such as diabetes or being postpartum. However, DMPA was not associated with increased risk for ATE, and other progestin-only methods were generally not associated with increased risk for ATE or VTE, among women with thrombogenic conditions [20].

The accumulating evidence that risk for VTE may vary among different progestin-only contraceptive methods was used to update several recommendations for conditions that also increase VTE risk (Tables 2–3) [20]. For several conditions, this resulted in recommendations that are different for DMPA than for LNG-IUD, implant, and POPs. Some changes reflect decreased safety concerns for LNG-IUD, implant, and POPs, including a change from U.S. MEC 3 to U.S. MEC 2 for systemic lupus erythematosus with positive or unknown antibodies, and changes from U.S. MEC 2 to U.S. MEC 1 for major surgery with prolonged immobilization. Other changes reflect increased safety concerns for DMPA, including changes from U.S. MEC 2 to U.S. MEC 3 for thrombophilia and peripartum cardiomyopathy (moderately or severely impaired), and changes from U.S. MEC 1 to U.S. MEC 2 during some of the earlier postpartum periods among women with risk factors for VTE, and for superficial venous thrombosis, complicated valvular heart disease, and peripartum cardiomyopathy (normal or mild impairment).

For women with solid organ transplantation, concern has focused on immunosuppression and the potential for increased risk for pelvic infection and decreased effectiveness with IUD use [46]. Accumulating evidence from more recent, higher quality studies has not supported these concerns [47]. No pelvic infections or pregnancies were observed among women with solid organ transplantation in four new non-comparative cohort studies of IUD users [48–51], and data from a new comparative cohort study suggested that LNG-IUD use among women with solid organ transplantation is effective, based on endometrial markers of local inflammatory response [52]. While direct evidence among women with solid organ transplantation remains limited, a systematic review of women with HIV, another immunosuppressed state, did not find increased risk for pelvic infection associated with IUD use [53]. Evidence is very limited for use of other contraceptive methods among women with solid organ transplantation. Many women with solid organ transplantation are at increased risk for cardiovascular disease, due to conditions such as diabetes, hypertension, and hyperlipidemia [54,55], and theoretical concerns remain about risk for thromboembolism with CHC and DMPA use for these women. Additionally, osteoporosis and fracture risk are increased in patients with end-stage organ disease and in the early post-transplant period, which may be further increased with long-term immunosuppressive therapy [56,57]. Therefore, DMPA use, which is associated with small decreases in bone mineral density, may further increase this risk [34].

Recommendations were updated for women with solid organ transplantation for IUDs (copper and LNG) and for DMPA (Tables 2–3). Updated U.S. MEC guidance recommends that IUDs can generally be used by women with solid organ transplantation (U.S. MEC 1 or U.S. MEC 2). Specifically, for women with graft failure, recommendations for initiation of an IUD (copper or LNG) were changed from U.S. MEC 3 to U.S. MEC 2. For continuation of an IUD among those with graft failure, and initiation and continuation of the IUD among those with no graft failure, recommendations changed from U.S. MEC 2 to U.S. MEC 1. For DMPA use among women with solid organ transplantation (with and without graft failure) who are receiving long-term immunosuppressive therapy with a history of or risk factors for non-traumatic fractures, the recommendation changed from U.S. MEC 2 to U.S. MEC 3; otherwise, DMPA for women with solid organ transplantation remains U.S. MEC 2.

Because hormonal contraception is metabolized by the liver, there may be concern that use of hormonal contraception among women with liver disease could worsen liver function or affect liver disease progression. While evidence suggests that hormonal contraceptive use among women with viral hepatitis (specifically hepatitis B or C) does not increase progression or severity of disease, no evidence is available for effects of hormonal contraception among women with cirrhosis [58]. One theoretical concern about hormonal contraceptive use among women with cirrhosis, especially decompensated cirrhosis, is that metabolism of contraceptive hormones might be impaired due to cirrhosis. Impaired metabolism of hormonal contraception could lead to increased circulating hormone levels and subsequent increased risk for adverse events, such as thromboembolism. This risk could be greater for estrogen-containing methods and DMPA, which are associated with increased risk for thromboembolism in the general population [7,9,20].

Recommendations for women with decompensated cirrhosis changed from U.S. MEC 3 to U.S. MEC 2 for LNG-IUD, implants, and progestin-only pills (Table 3); DMPA remains U.S. MEC 3, CHCs remain U.S. MEC 4, and copper IUD remains U.S. MEC 1. Recommendations for compensated cirrhosis remain U.S. MEC 1 for all methods.

U.S. MEC provides recommendations for liver tumors, including benign tumors (hepatocellular adenoma and focal nodular hyperplasia) and malignant tumors (hepatocellular carcinoma). Updated evidence for the effects of hormonal contraceptive use on liver tumors continued to suggest that hepatocellular adenomas are generally estrogen responsive, with tumor progression more likely among COC users than non-users, and decreases in tumor size with COC discontinuation [58]. However, accumulating evidence suggests that hepatocellular adenoma tumor size changes among progestin-only contraceptive users were similar to non-users, and that hepatocellular adenomas generally regress or remain stable with progestin-only contraceptive use [58]. As found in previous reviews, changes in focal nodular hyperplasia tumors were generally independent of hormonal contraceptive use, and no evidence was identified for hepatocellular carcinoma [58].

Among women with liver tumors, recommendations for those with hepatocellular adenoma changed from U.S. MEC 3 to U.S. MEC 2 for LNG-IUD, implants, and POPs, based on the additional evidence that hepatocellular adenoma growth was not associated with progestin exposure (Table 3); DMPA remains U.S. MEC 3, and CHCs remain U.S. MEC 4. Recommendations remain the same for focal nodular hyperplasia (U.S. MEC 1 for copper IUD and U.S. MEC 2 for all hormonal methods) and for hepatocellular carcinoma (U.S. MEC 1 for copper IUD, U.S. MEC 3 for all progestin-only methods including LNG-IUD, and U.S. MEC 4 for CHCs).

While postpartum IUD placement is safe, there is increased risk for expulsion when the IUD is placed immediately postpartum, which may leave a woman without contraception [59]. However, data on both absolute and relative risk for expulsion has been limited and varied [59]. Data from a previous review suggested that IUD expulsion rates with immediate post-placental placement (< 10 minutes after delivery of the placenta) were lower than with placement 10 minutes to less than 4 weeks, but still higher than with interval placement (4 weeks postpartum or later) [59]. Three more recent pooled analyses of expulsion rates show that while there is variability in expulsion rates at different times of placement during the postpartum period, rates for all postpartum time periods are substantially greater than rates with interval placement [60–62]. In one of the pooled analyses, rates of expulsion were 8.6% (range among studies 0.03–31.9%) for immediate placement, 25.1% (range 3.5–46.7%) for placement greater than 10 minutes and less than 72 hours, and 4.5% (range 0.0–46.7%) for placement greater than 10 minutes and less than 4 weeks, compared with 1.6% (range 0.0–4.8%) for interval placement [61].

Recommendations for immediate IUD placement (< 10 minutes after delivery of the placenta) changed from U.S. MEC 1 to U.S. MEC 2 for copper IUDs (regardless of breastfeeding status) (Table 2). For LNG-IUDs, the recommendation changed from U.S. MEC 1 to U.S MEC 2 for women who were not breastfeeding (Table 2); for women who were breastfeeding, the recommendation remained U.S. MEC 2. A clarification of the recommendation states that postpartum placement of IUDs is safe and does not appear to increase health risks associated with IUD use such as infection. Higher rates of expulsion during the postpartum period should be considered as they relate to effectiveness along with patient access to interval placement when expulsion rates are lower.

There is potential for drug-drug interactions between hormonal contraception and mifepristone (an anti-progestin) regimens [63]. Evidence from a randomized clinical trial suggests that while there was no difference in risk for ongoing pregnancy with immediate versus delayed start of contraceptive implants, there was a higher percentage of ongoing pregnancies with immediate versus delayed DMPA administration (3.6% vs 0.9% respectively, difference 2.7%; 90% CI 0.4–5.6%) [63–65].

Given the evidence about a possible interaction between mifepristone and DMPA, the recommendation for DMPA use after first trimester medication abortion with a regimen that includes mifepristone was changed from U.S. MEC 1 to U.S. MEC 2 (Table 2). An accompanying clarification states that concurrent administration of DMPA with mifepristone might slightly decrease medication abortion effectiveness and increase risk for ongoing pregnancy, and risk for ongoing pregnancy with concurrent administration of DMPA with mifepristone should be considered along with personal preference and access to follow-up abortion and contraceptive care. All other post-abortion recommendations remain U.S. MEC 1 or U.S. MEC 2, with the exception of U.S. MEC 4 for IUD placement in the setting of postseptic abortion.

Several new contraceptive methods were added to the 2024 U.S. MEC [1]. Most were new doses or formulations of existing methods, such as COCs, contraceptive patches, vaginal rings, POPs, and LNG-IUDs. New COCs include estradiol valerate or estetrol as the estrogen component. While these newer estrogens are less potent than ethinyl estradiol and may be less thrombogenic [66], recommendations are the same for all COC formulations, pending more data on the thrombotic risk associated with these newer formulations. Drospirenone POPs were also added; all U.S. MEC recommendations for drospirenone POPs are the same as for norethindone and norgestrel POPs, with the exception of those described in Section 3.2 for CKD. In addition, a vaginal pH modulator was added as a new barrier method, with all recommendations either U.S. MEC 1 or U.S. MEC 2.