Progesterone Metabolites: a-Pregnanediol and b-Pregnanediol

Progesterone Metabolites: Pregnanediol

Progesterone does not show up in urine as progesterone. Rather it appears as two metabolites, alpha-pregnanediol and beta-pregnanediol, and together they show how much you made after ovulation and if ovulation took place.

The split between these two metabolites is important: alpha-pregnanediol is metabolised down the same 5-alpha pathway as DHT, and it leads to allopregnanolone, the metabolite that acts on GABA receptors and does most of progesterone’s calming work. Two women with identical total progesterone can feel very different depending on how much of it takes that route. If you have not tested yet, both metabolites are measured in all three FUTURE WOMAN tests.

Let’s take a closer look at what the two progesterone metabolites are, why optimal levels matter, and how it can impact your health.

What is Progesterone?

Progesterone is an endogenous steroid hormone primarily produced by the ovaries, specifically by the corpus luteum (the degraded follicle that released your egg) following ovulation. It is also secreted in smaller amounts by the adrenal cortex. During pregnancy, progesterone production transitions to the placenta after the first 10-13 weeks. Progesterone levels peak during the luteal phase of the menstrual cycle, approximately 5–7 days after ovulation.

Why We Need Progesterone:

  • Endometrial preparation: Progesterone plays a key role in preparing the uterine lining (endometrium) for implantation of a fertilised egg.
  • Estrogen balance: It counteracts the effects of estrogen, maintaining hormonal balance.
  • Neurosteroid action: Progesterone acts on the brain, influencing mood, behaviour and sleep.
  • Diuretic effect: It can reduce fluid retention.
  • Temperature regulation: Progesterone raises basal body temperature after ovulation.

Progesterone Metabolites

Progesterone is metabolised (the pathway progesterone takes in order to leave the body) into two main urinary metabolites: alpha-pregnanediol (a-Pregnanediol) and beta-pregnanediol (b-Pregnanediol). These metabolites provide a reliable indication of total progesterone levels and correlate strongly with serum progesterone.

Alpha-Pregnanediol (a-Pregnanediol):

  • Produced via the 5-alpha reductase pathway, which leads to the formation of allopregnanolone, a neurosteroid with anti-inflammatory and calming effects.
  • Allopregnanolone interacts with GABA-A receptors in the brain and immune cells, promoting sedative, anxiolytic, and neuroprotective properties. 

Beta-Pregnanediol (b-Pregnanediol):

  • Produced via the 5-beta reductase pathway, resulting in less active progesterone metabolites.
  • While b-Pregnanediol is the predominant metabolic endpoint of progesterone, it has little biological activity.

Measuring both these metabolites can give other information about your health.  The two pathways are analogous to the pathway options for testosterone. Women with PCOS/PMOS, or those that suffer from symptoms such as acne, hair loss and excess body hair, tend to push testosterone down the alpha pathway towards the more potent DHT. These women will also tend to push progesterone down its alpha pathway. Patients with hypothyroidism, on the other hand, tend to push much more heavily down the beta pathway.

Combined Metabolite Insights:

Both a-Pregnanediol and b-Pregnanediol represent major progesterone metabolic endpoints. Together, they provide a comprehensive picture of total progesterone production. Your practitioner will have taken this all into account in your report. 

Symptoms of High and Low Progesterone

The reference ranges for progesterone metabolites are:

  • Luteal phase a-Pregnanediol: 200–740 ng/mg
  • Luteal phase b-Pregnanediol: 600–2000 ng/mg
  • Postmenopausal a-Pregnanediol: 15–50 ng/mg
  • Postmenopausal b-Pregnanediol: 60–200 ng/mg

High Progesterone Levels:

Elevated progesterone may indicate:

  • Pregnancy
  • Ovarian cysts
  • Hormone replacement therapy (HRT)
  • Stress
  • Rarely, ovarian cancer or congenital adrenal hyperplasia (CAH)

High progesterone levels can be associated with:

  • Breast tenderness
  • Abdominal cramping
  • Back pain
  • Vaginal bleeding
  • Dizziness due to low blood pressure 

Low Progesterone Levels:

Progesterone levels naturally decline during perimenopause (even starting to lower around 35), and women with certain conditions that affect HPO function such as PCOS, hypothalamic amenorrhea, (often from undereating or over-exercising), hypothyroidism, hyperprolactinemia and low cholesterol may also exhibit lower levels of progesterone due to irregular ovulation and general low hormone levels. Other reasons for low progesterone include taking hormonal contraception (which suppresses natural progesterone), chronic stress, underlying infections and inflammation. 

Low progesterone levels are associated with:

  • Estrogen dominance, which may present with PMS symptoms including:
    • Heavy or painful periods
    • Breast tenderness, and bloating.
    • Anxiety or mood swings
    • Insomnia
  • Menstrual irregularities, such as amenorrhea (absence of periods) or menorrhagia (heavy periods).
  • Fertility challenges, due to insufficient endometrial preparation for implantation.
  • Pregnancy complications: Progesterone levels below 10 ng/mL at 6–8 weeks may suggest abnormal intrauterine or ectopic pregnancies.

Progestins vs progesterone

Whilst progesterone is made naturally in the body after ovulation, progestins are synthetically made and are found in hormonal contraception including the pill, IUDs and implants. They have the same favourable thinning effect on the menstrual lining (helping to manage heavy periods), but they have opposite effects in most other parts of the body, including the breasts and brain. Taking progestins will also lower or suppress the body’s production of natural progesterone, which can affect mood, sleep and cause PMS symptoms from estrogen dominance. 

Oral progesterone

Oral micronized progesterone, which is body-identical unlike progestins, is often taken in perimenopause and menopause to help with symptoms such as hot flushes, anxiety and insomnia. Progesterone metabolites can be measured to individualise and optimise progesterone levels, although it is important to note it is not possible to measure what is your own endogenous progesterone or what is exogenous. 5α-pregnanediol is of particular interest due to its ability to cross the blood-brain barrier, acting as a precursor to allopregnanolone, which binds GABA-A receptors. This interaction underlies the calming and sedating effects of progesterone, especially when orally supplemented.

Oral progesterone and estrogen

Research suggests that progesterone may act as an estrogen antagonist by downregulating the activity of estrogen receptors in the body. While this effect can be beneficial in uterine tissue, helping to alleviate symptoms of high oestrogen, it can also reduce oestrogen receptors in the brain and other areas of the body. As a result, it can lead to lower levels of estrogen in comparison to progesterone, which can lead to new symptoms and even an earlier need for HRT. 

Which tests measure the two progesterone metabolites?

Both metabolites are measured in all three of our tests: the Classic Hormone Test, the Advanced Hormone Test and the Advanced+ Hormone Test with Cycle Mapping.

If you are not sure which test you need, our comparison guide walks through the differences.

Next steps

If your results suggest high or low progesterone, this will be addressed in your personalised health plan by one of our experienced nutritionists. If you would like to learn more about your test results, remember you can purchase a 45 minute Hormone Health Consultation with your practitioner to discuss your results in more detail.

References

Bimonte-Nelson, H. A., Nelson, M. E., & Granholm, A. C. (2004). Progesterone counteracts estrogen-induced increases in neurotrophins in the aged female rat brain. Neuroreport, 15(17), 2659–2663. https://doi.org/10.1097/00001756-200412030-00021

Cable JK, Grider MH. Physiology, Progesterone. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK558960/

Haufe, A., & Leeners, B. (2023). Sleep Disturbances Across a Woman’s Lifespan: What Is the Role of Reproductive Hormones?. Journal of the Endocrine Society, 7(5), bvad036. https://doi.org/10.1210/jendso/bvad036

Hsuea, A., Peck, E. & Clark, J. (1975).Progesterone antagonism of the oestrogen receptor and oestrogen-induced uterine growth. Nature 254, 337–339. https://doi.org/10.1038/254337a0

Kimball, A., Dichtel, L. E., Nyer, M. B., Mischoulon, D., Fisher, L. B., Cusin, C., Dording, C. M., Trinh, N. H., Yeung, A., Haines, M. S., Sung, J. C., Pinna, G., Rasmusson, A. M., Carpenter, L. L., Fava, M., Klibanski, A., & Miller, K. K. (2020). The allopregnanolone to progesterone ratio across the menstrual cycle and in menopause. Psychoneuroendocrinology, 112, 104512. https://doi.org/10.1016/j.psyneuen.2019.104512

Memi, E., Pavli, P., Papagianni, M., Vrachnis, N., & Mastorakos, G. (2024). Diagnostic and therapeutic use of oral micronized progesterone in endocrinology. Reviews in endocrine & metabolic disorders, 25(4), 751–772. https://doi.org/10.1007/s11154-024-09882-0

Murphy, D. D., & Segal, M. (2000). Progesterone prevents estradiol-induced dendritic spine formation in cultured hippocampal neurons. Neuroendocrinology, 72(3), 133–143. https://doi.org/10.1159/000054580

Prior, J. C. (2018). Progesterone for perimenopausal hot flushes—A useful option. Gynecological Endocrinology, 34(4), 289-293.

Standeven, L. R., McEvoy, K. O., & Osborne, L. M. (2020). Progesterone, reproduction, and psychiatric illness. Best practice & research. Clinical obstetrics & gynaecology, 69, 108–126. https://doi.org/10.1016/j.bpobgyn.2020.06.001

Sundström-Poromaa, I., Comasco, E., Sumner, R., & Eileen Luders, E. (2020). Progesterone – Friend or foe? Frontiers in Neuroendocrinology, 59, 100856.

https://doi.org/10.1016/j.yfrne.2020.100856.
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