Table 1.

Contraceptives for the management of menstruation associated SCD pain

Therapy	Mechanism of action*	Route of administration	Clinical evidence in SCD	Comments
Progestin-only therapies Primary mechanism of pregnancy prevention is thickening of cervical mucus.			Legardy, et al. 2006 [17] Yoong et al. 1999 [10]	No SCD adverse events, hematologic or other biochemical adverse parameters, and no thrombosis have been reported with any of the progestin-only methods.
Depot medroxyprogesterone (DMPA)	LARC Suppress ovulation	Intramuscular injection every 3 months	de Abood et al., 1997 [7] De Ceulaer et al., 1982 [34] Howard et al., 1993 [35]	• Associated with a decrease in menstruation associated SCD pain and frequency. • Side effects: unscheduled bleeding, weight gain, and bone mineral density loss over time. • Higher risk of VTE in the general population, compared with no use CDC MEC 2024 Category 2/3 [34]**
Levonorgestrel (LNG) IUD	LARC Suppress Menstruation & inconsistently suppress ovulation	Intrauterine device every 5–8 years	Howard et al., 1993 [35]	• High rates of amenorrhea and contraception are achieved with the LNG IUD. CDC MEC 2024 Category 1
Etonogestrel (ENG) implant	LARC Suppress ovulation for 3 years and prevents pregnancy for 5 years	Subcutaneous implant every 5 years	Nascimento et al.1998 [21] Ladipo et al. 1993 [22]	• Nomegestrel acetate resulted in a decline in headaches, body weakness, and limb pain in persons with SCD. • Studies with ENG implant and SCD are ongoing. • Unscheduled bleeding and spotting can be unpredictable leading to a higher rate of discontinuation compared with other LARCs. CDC MEC 2024 Category 1
Progestin only pill (Norethindrone, Drospirenone)	Inconsistent suppression of ovulation	Oral, daily	Howard et al. 1993 [35]	• Small therapeutic window to maintain the full contraceptive benefits. • Can result in intermittent bleeding. CDC MEC 2024 Category 1
Other hormonal and non-hormonal therapies
Combined hormonal contraceptive (CHC)	Suppress ovulation and produce a regular consistent bleeding pattern	Oral pill, transdermal patch, and vaginal ring	de Abood et al. 1997 [7] Howard et al. 1993 [35] Yoong et al. 1999 [10]	• Few studies evaluate have evaluated CHCs in SCD. • CHCs are associated with a relative increased risk for VTE compared to non-users in the general population. • SCD is a high-risk thrombophilia and CHCs are generally avoided in this population. *A thoughtful discussion and shared decision making weighing the risks and benefits should be had when considering CHC use in SCD. CDC MEC 2024 Category 4
Copper (Cu) IUDs	Copper ions prevent sperm mobilization	Intrauterine device every 10 years	N/A	• Can lead to worsening menstrual cramps and increased bleeding, so it is generally not ideal for use in persons with SCD. CDC MEC 2024 Category 2 (Concern exists about an increased risk of blood loss with Cu-IUDs)

CHC, combined hormonal contraceptive; POP, progestin only pill; DMPA, depot medroxyprogesterone; ENG Implant, Subdermal Etonogestrel Implant; CU-IUD, copper intrauterine device; LNG-IUD, levonorgestrel intrauterine device.

U.S. MEC Category 1 = A condition for which there is no restriction for the use of the contraceptive method.

U.S. MEC Category 2 = A condition for which the advantages of using the method generally outweigh the theoretical or proven risks.

U.S. MEC Category 3 = A condition for which the theoretical or proven risks usually outweigh the advantages of using the method.

U.S. MEC Category 4 = A condition that represents an unacceptable health risk if the contraceptive method is used.

*Mechanism of action for menstrual suppression and prevention of pregnancy.

** It should be assessed according to the severity of SCD and risk of thrombosis.