Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease

Inclusion Criteria: 1. Provision of signed and dated informed consent form 2. Female, aged 18-50 years old 3. Diagnosis of sickle cell disease (SS, SB0,SB+,SC) 4. Report of at least 1 vaso-occlusive pain episode per month on average in the previous 6 months 5. At least 1 and no more than 10 medical presentations (e.g. hospitalization, emergency room visit, outpatient infusion visit) for sickle cell-related pain during the past year 6. Willing to discontinue any hormonal contraception at the time of enrollment. Washout period of 1 month since last use of all hormonal contraception, and 4 months since most recent administration of depot medroxyprogesterone, is required prior to enrollment in the study. 7. Have regular menstrual cycles (when not on hormonal contraception) with a usual length of 21 to 35 days. 8. Stable dose of hydroxyurea and other sickle cell-related medications for the past 6 months 9. Access to a device with text-messaging capability 10. Must be able to read and understand English 11. Willing to comply with study procedures Exclusion Criteria: 1. Chronic inflammatory conditions, such as lupus or inflammatory bowel disease 2. History of VTE or stroke 3. Current use of crizanlizumab, voxelotor, or red cell exchange transfusion, or history of hematopoietic stem cell transplantation 4. Current use of hormonal contraception or the copper intrauterine device 5. Current pregnancy or pregnancy within the last 6 months 6. Current lactation 7. Polycystic ovary syndrome or irregular periods 8. Blood pressure \>= 160 systolic or \>=100 diastolic at screening visit