There is evidence to suggest that DHEA-based treatment could be beneficial to patients with asthma, yet one of the main treatments for asthma (taking glucocorticoids, a hormone that is effective in reducing inflammation), suppresses the production of DHEA.

In this study, the investigators want to test and evaluate the safety of DHEA-based treatment.

During this study, participants will come to the study site 4-5 times and have 2 telephone visits over a period of approximately 3 months. Participants will complete the following:

Informed Consent: Coordinators will explain the study to participants. If participants decide to participate, they will be asked to review, sign, and date the consent form.

Medical History: Coordinators will review participants medical chart and record relevant medical history, including the history of asthma, other pertinent respiratory details, and any information regarding underlying diseases such as cystic fibrosis or chronic lung disease. Coordinators will also ask participants about any medications they are currently taking.

Demographic Information: Coordinators will collect information about participants such as age, gender, and race.

Physical Exam & Vital Signs: The study doctor will examine the participants head, eyes, ears, nose, throat; heart, chest, lungs, and abdomen; extremities and skin; and any other areas as appropriate for any abnormal signs and symptoms. In addition, they will also check participants vital signs which includes measuring blood pressure, temperature, heart rate, breathing rate, pulse oximetry (the amount of oxygen in the blood), and height and weight.

Urine Samples: All participants will be asked to provide a urine sample that will be tested for cotinine levels (to indicate whether participant has been exposed to nicotine recently).

Pregnancy Testing & Contraception Females who can get pregnant will also have a pregnancy test. Because DHEA is a hormone and it is not known how it will affect a developing baby, if the participant is pregnant, they cannot be in this study. Additionally, they must practice a medically acceptable form of contraception during study participation. Medically acceptable contraceptives include: (1) surgical sterilization, (2) approved hormonal contraceptives such as birth control pills, (3) barrier methods (such as a condom or diaphragm) used with a spermicide, (4) abstinence, or (5) an intrauterine device (IUD).

Blood Samples: At each in-person visit, the study team will draw up to 40ml (about 8 teaspoons) of the participants blood to assess overall blood health (complete blood count, or CBC), metabolic and organ function (comprehensive metabolic panel), hormone levels, and immune system activity (cytokine responses and peripheral blood mononuclear cells or PBMCs). The study team will also use the participants blood sample for genotyping (studying genetic makeup), their ability to process DHEA; and measuring the level of DHEA-S. For male subjects, a portion will be used for a Prostate Specific Antigen Test, which checks for prostate cancer.

Spirometry: This test measures how much air a persons lungs can hold and how fast they can breathe out. Participants will take a deep breath and then blow into a mouthpiece as hard as possible and for as long as possible. They might have to wear soft nose clips during the test to stop air from escaping through the nose. They will be asked to repeat this test at least 3 times. They will be asked to take a bronchodilator (a medication that relaxes and opens the airways in the lungs) such as albuterol while completing spirometry during some study visits. The study team will provide the bronchodilator used for the test.

Methacholine Challenge Testing (MCT): This test will be done only if the participant failed to demonstrate 10% reversibility in Forced Expiratory Volume in 1 Second (FEV1) and there are no historical MCT results available.

MCT is done to confirm that the participant has asthma. Methacholine is approved by the FDA. When methacholine is inhaled, it causes the airways to spasm (contract involuntarily) and narrow if asthma is present. During this test, the participant will inhale increasing amounts of methacholine aerosol mist before and after spirometry. The MCT is considered positive, meaning asthma is present, if the participants lung function drops by at least 20%.

If the participants airways tighten at any point, they will be given albuterol to open their airways. Often, the staff person doing the test will know that the participants airways are tightening before they feel it, by seeing a drop in the test results. A bronchodilator is always given at the end of the test to reverse the effects of the methacholine.

Completion of Questionnaire & Symptom Diary: Participants will be asked to complete the Asthma Control Test (ACT) and the Asthma Control Questionnaire (ACQ) at several study visits. They will also be asked to complete a medication dosing and symptom diary at home between visits 1 and 3 and visits 4 and 6.

Randomization: Participants will be randomly assigned (like flipping a coin) to receive either DHEA or placebo.

Study Drug: DHEA is an over-the-counter supplement that is available on the market without prescription. In this study, the participants will be taking DHEA or placebo as a capsule that has been formulated in a specific way that the investigators expect will make it as effective as possible. The participants will be provided enough capsules for the four-week window of administration.

At Visits 3 and 6, the participants will please return all unused DHEA capsules and packaging to the study team.

There is also one unscheduled visit that will be used in case the participant needs to return to the study site for any reason to finish study activities.

Inclusion Criteria:

1. Adult male or female age ≥ 18 and ≤ 50 years at the time of enrollment

2. Evidence of asthma demonstrated by reversibility at visit 0 or by historical methacholine or bronchodilator reversibility if testing was performed under either the 2017 European Respiratory Society (ERS) technical standard (22) or the 1999 American Thoracis Society (ATS) Guidelines (23) or outside studies, provided that full sets of flow volume loops have been reviewed and approved by the PI. These criteria are defined as one of the following:

   1. For bronchodilator reversibility: An increase in FEV1 ≥ 10% (24) compared to the baseline (and 200 ml) after up to 8 puffs of albuterol
   2. For historical methacholine responsiveness: Positive methacholine defined as Provocative Concentration of Methacholine causing a 20% fall in FEV1 (PC20) ≤ 16 mg/ml, or Provocative Dose of Methacholine causing a 20% fall in FEV1 (PD20) ≤ 400 mcg

3. Physician diagnosis of asthma according to NHLBI guidelines

4. Consistent use of an Inhaled Corticosteroids (ICS) inhaler for the prior 2 months

5. Non-smoker

6. Females must not be pregnant or breastfeeding

7. Absence of non-allergic comorbidities

Exclusion Criteria:

1. Pregnant or actively trying to become pregnant; breastfeeding
2. Positive urine pregnancy test
3. Known lung disease other than asthma
4. Acute (non-asthma related) dyspnea, viral respiratory illness or asthma exacerbation within 4 weeks of screening
5. Systemic glucocorticoid dosing for maintenance >10 mg/day of prednisone or equivalent
6. Patients with significant non-allergic comorbidities (e.g. cerebral palsy, heart disease, kidney disease, liver disease, etc.)
7. Patients with any know central or peripheral endocrine abnormality such as precocious puberty or diabetes
8. Patients with any known previous adverse reaction to DHEA
9. Current smoker or pack year history > 5 years (includes vaping/nicotine inhalation devices)
10. Positive urine cotinine test (> 100 mg/mL)
11. Use of prednisone or antibiotics in the last 4 weeks
12. Use of any performance-enhancing drugs in the last 2 weeks
13. Use of DHEA in the last 2 weeks
14. Androgen use for any reason.
15. Any other condition or finding that would compromise the safety of the subject or the quality of the study data, or otherwise interfere with achieving the study objectives, as determined by the PI
16. Menopausal amenorrhea by history
17. Positive Prostate-Specific Antigen (PSA) (>4 ng/ml) test
18. Prior diagnosis of vocal cord dysfunction, bronchopulmonary dysplasia, cystic fibrosis, chronic obstructive pulmonary disorder, or other lung disease
19. Systolic blood pressure > 150 mm Hg and/or diastolic blood pressure >90 mm Hg
20. Heart rates outside the range of 50 to 120 beats per minutes or with a pathologic irregularity
21. Patients afflicted with any additional acute or chronic pathology that in the opinion of the screening physician makes them unsuitable for study or increases the risks associated with the study.

Pharmacy will maintain mask