How DHEA Supplements Affect Coagulation in Women Using Birth Control Pills
Condition: Contraceptive Usage; Coagulation
Study type: Interventional
Phase: Phase 4

Summary: 
      A randomized study is to learn more about how a supplement called DHEA
      (dehydroepiandrosterone) affects clotting factors in women taking combined oral contraceptive
      pills. Current research suggests that the progestin hormone in a specific type of birth
      control pill may increase a woman's blood clot risk. However, it is unknown exactly how the
      progestin causes the increased risk. This study aims to learn if taking a daily dose of
      supplemental androgen (dehydroepiandrosterone, or DHEA) in addition to birth control pills
      containing DRSP affects proteins related to coagulation.
    

Detailed description: 
      While the pro-thrombotic effects of estrogens are well established in women using combined
      oral contraception (COC), controversy exists over whether the various synthetic progestogens
      (progestins) used in combination with ethinyl estradiol in COC formulations may modify the
      risk of venous thromboembolism (VTE). Several studies have demonstrated that different types
      of progestins used in COCs influence the magnitude of the estrogen-induced changes in
      coagulation pathway proteins. However, since hepatocytes do not express progesterone
      receptor, any activity of a progestin must be indirect. While all progestins on the market
      are strong agonists for the progesterone receptor (PR), most have variable affinity for the
      androgen receptor (AR), glucocorticoid receptor (GR), and mineralocorticoid receptor (MR).
      Generations of progestins have been developed, each successive generation exhibiting
      decreasing levels of androgenicity. Recent epidemiologic studies have suggested an increased
      risk of VTE in women using low-androgen progestins relative to those using
      levonorgestrel-containing products. Although no pattern of hepatic globulin changes has been
      validated as a surrogate marker for thrombosis risk, the overall magnitude of change in
      various hepatic proteins involved in coagulation is greater with the newer low-androgenic
      progestins compared to levonorgestrel, leading some experts to suggest that a progestin's
      androgenic profile may influence the risk of thrombosis. However, a series of well-designed
      large prospective cohort studies have not confirmed the increased risk of VTE with
      low-androgen progestins.

      A major problem with reconciling the conflicting results from epidemiologic and prospective
      studies has been the lack of a clear mechanism, as no studies have demonstrated whether these
      observed changes are mediated through androgen receptor activity. We hypothesize that
      androgen receptor activity opposes the estrogen receptor-mediated increase in hepatic
      clotting factors in women using combined oral contraceptives. To test this hypothesis, we
      propose a randomized clinical trial in which we will enroll healthy women using combined oral
      contraception containing ethinyl estradiol (EE) with an antiandrogenic progestin
      (drospirenone, DRSP). Participants will be randomized to treatment with oral androgen
      (dehydroepiandrosterone, DHEA) or placebo, and we will collect whole blood samples to measure
      coagulation pathway-related hepatic globulins (APC-r, Protein S, SHBG) before and after
      treatment.
    

Intervention name(s): DHEA Oral Capsule; Placebo Oral Capsule
Intervention type(s): Dietary Supplement; Other
Intervention description(s): Daily 100mg DHEA supplement; Daily oral capsule
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Oral contraceptives; Venous thromboembolism; androgenic combined oral contraception