Low Hydroxyprogesterone: Its Causes and Related Symptoms

Hydroxyprogesterone is a steroid hormone that serves as a building block for other hormones. In a medical context, the focus is on 17-hydroxyprogesterone (17-OHP), the most commonly measured and clinically relevant form. It is produced primarily in the adrenal glands, which are small organs that sit atop each kidney. Low levels of this hormone can signal underlying health issues related to its production.

The Role of Hydroxyprogesterone in Your Body

The primary function of 17-hydroxyprogesterone (17-OHP) is to act as a chemical intermediate, or precursor, for cortisol production inside the adrenal glands. Cortisol is a hormone that affects nearly every organ and tissue, helping to regulate metabolism, manage stress responses, and control inflammation. In this production pathway, 17-OHP is a component waiting for an enzyme to convert it into the next substance that eventually becomes cortisol.

While most 17-OHP is made in the adrenal glands, smaller amounts are also produced in the gonads—the testes in males and ovaries in females—where it contributes to sex hormone synthesis. Its availability is directly linked to the body’s need for cortisol. When more cortisol is required, the adrenal glands are stimulated to increase production, which includes making more 17-OHP.

Why Hydroxyprogesterone Levels Might Be Low

Low 17-hydroxyprogesterone (17-OHP) levels are uncommon and signal an issue with the adrenal glands’ hormone production. A primary cause is adrenal insufficiency. In primary adrenal insufficiency, also known as Addison’s disease, the adrenal glands themselves are damaged and cannot produce adequate amounts of hormones. This damage can result from autoimmune disorders, infections, or direct injury.

Another cause is secondary adrenal insufficiency, where the adrenal glands are healthy but do not receive the proper signals from the pituitary gland. The pituitary fails to secrete enough adrenocorticotropic hormone (ACTH), the chemical messenger that tells the adrenal glands to make cortisol. Without this signal, the entire adrenal hormone production line, including 17-OHP synthesis, slows down.

Rare genetic disorders can also cause low 17-OHP. In certain forms of congenital adrenal hyperplasia (CAH), an enzyme deficiency occurs before 17-OHP is created in the steroid synthesis pathway. Because the enzymes needed to make 17-OHP are absent, its concentration remains low.

Symptoms and Associated Health Conditions

Symptoms are not caused by low 17-OHP itself, but by the underlying medical conditions that disrupt its production. Most symptoms arise from adrenal insufficiency, which leads to a cortisol deficiency. These include:

• Chronic fatigue
• Pervasive muscle weakness
• Loss of appetite and unexplained weight loss
• Low blood pressure (hypotension)
• Cravings for salty foods due to electrolyte imbalances

Primary adrenal insufficiency (Addison’s disease) can cause hyperpigmentation, a distinctive darkening of the skin. This symptom is most noticeable in skin creases, scars, and on the gums. It helps differentiate primary from secondary adrenal insufficiency, as these skin changes do not occur in the latter.

Rare forms of congenital adrenal hyperplasia (CAH) that cause low 17-OHP present with a different set of signs. Because these genetic conditions can interfere with both cortisol and sex hormone production, they may affect sexual development. They can also cause hypertension and low potassium levels.

Diagnosis and Management of Low Hydroxyprogesterone

Diagnosing the cause of low 17-OHP begins with a blood test to measure its concentration. If levels are low, a broader panel of tests is used to measure related hormones like cortisol and ACTH, as well as electrolytes. The pattern of these results helps physicians distinguish between different types of adrenal disorders.

An ACTH stimulation test is a primary diagnostic tool for assessing adrenal function. During this test, a synthetic version of ACTH is administered to measure the adrenal glands’ cortisol response. A minimal or absent response is a strong indicator of primary adrenal insufficiency, while genetic testing can confirm rare forms of congenital adrenal hyperplasia (CAH).

Management focuses entirely on treating the underlying disorder. For primary and secondary adrenal insufficiency, the standard treatment is hormone replacement therapy with a glucocorticoid, such as hydrocortisone, to replace the missing cortisol. In primary adrenal insufficiency, a mineralocorticoid may also be needed to manage salt and water balance.

The management of rare CAH forms is highly specialized and tailored to the specific enzyme deficiency and its effects on hormone production. All of these conditions require consistent, long-term medical supervision to monitor hormone levels, adjust medication, and manage symptoms effectively.