The word progesterone means “promoting gestation,” and progesterone is often considered a female hormone since high progesterone levels are present during healthy pregnancy. But - progesterone is also an important hormone that supports fertility and general health in men.1 In fact, progesterone is the most abundant hormone produced by the reproductive glands.2
In women, progesterone is primarily synthesized by the corpus luteum in the ovary during the second half of the menstrual cycle (after ovulation), the adrenal glands daily, and the placenta during pregnancy. In men, progesterone, which is a precursor for testosterone production, is predominately produced by the adrenal glands and the testes.2 Continue reading below to learn more about the beneficial effects of optimal salivary progesterone levels on fertility in women and men.
Progesterone Production – The Steroidogenesis Pathway
Progesterone is a steroid hormone produced via steroidogenesis, which is the natural production of steroid hormones. Steroid hormone synthesis begins with the enzymatic conversion of cholesterol to the hormone pregnenolone in your mitochondria. Enzymes then further convert pregnenolone to all other steroid hormones, including progesterone and testosterone. Each steroid hormone-producing tissue in your body has the specific enzymes necessary for the production of the steroid hormones required by the tissue.3
Here is a picture of the steroid hormone production pathways:
As you can see in the image above, progesterone (P1) is an essential precursor of many other reproductive and non-reproductive hormones, including aldosterone, cortisol, estradiol, and testosterone.1 Optimal P1 levels are crucial for fertility, balanced mood, healthy gut function, immune health, nerve function, bone strength, and more in women and men.
Fertility in Women – Progesterone Levels during the Menstrual Cycle and Pregnancy
Progesterone (P1) plays a significant role in fertility, and ample amounts of P1 are required for a healthy pregnancy. A woman must release at least one egg (oocyte) from an ovary during an ovulatory menstrual cycle to be fertile. An average menstrual cycle lasts approximately 28 days, and ovulation, which is the release of an egg, tends to occur around Day 14 of a 28-day menstrual cycle.
During the follicular phase of the menstrual cycle - the first half of the menstrual cycle before ovulation - egg-containing follicles in the ovary develop and mature until one special follicle is chosen for ovulation. The chosen follicle is the dominant follicle. During ovulation, the dominant follicle in the ovary ruptures, and the egg is released, which begins the second half of the menstrual cycle – the luteal phase.
Once released, the egg travels from the ovary into the fallopian tube and eventually into the uterus, where, if fertilized, the fertilized egg can continue to develop into a fetus.
The ruptured follicle left behind in the ovary after ovulation is the source of most of the progesterone released during a menstrual cycle. Once the egg is released, the ruptured follicle becomes a hormone-releasing “corpus luteum” in the ovary. The picture below illustrates the corpus luteum in the ovary on the left and the released egg traveling through the fallopian tube into the uterus:
The menstrual cycle and ovulation can be visualized by looking at the hormone levels throughout a menstrual cycle in a healthy woman. Here is an example of salivary estradiol and progesterone levels during a healthy ovulatory 28-day menstrual cycle:
Can you guess when ovulation occurred by looking at the graph above?
If you guessed approximately Day 14 (or 15) - you are correct! The progesterone level nearly doubles between Day 13 and Day 15, then continues to significantly increase during the luteal phase of the menstrual cycle after ovulation. All of the extra progesterone present during the second half of the menstrual cycle is released by the corpus luteum in the ovary. Thus, when progesterone levels are much higher during the second half of a menstrual cycle, we know ovulation occurred; and pregnancy is possible.
Therefore, measuring salivary hormone levels throughout a menstrual cycle is a non-invasive testing option for assessing fertility status in women.
The image below illustrates the changes in the ovarian follicle and the lining of the uterus (endometrium) during a healthy menstrual cycle:
What is the Purpose of High Progesterone Levels After Ovulation?
The corpus luteum in the ovary releases robust amounts of progesterone (P1) after ovulation to support reproduction and healthy pregnancy. Sperm must be exposed to high levels of P1 in the female genital tract for sperm capacitation and the acrosome reaction to occur, which are required for the fertilization of the egg.3 Sperm capacitation and the acrosome reaction are discussed in more detail below.
The robust levels of P1 also prepare the lining of the uterus (endometrium) for implantation of the fertilized egg and maintain the early pregnancy until the placenta develops and begins producing P1. Plentiful P1 is so crucial for the support of pregnancy that the removal of P1 in early pregnancy induces a miscarriage.4
Thus, high P1 levels are required for optimal fertility and healthy pregnancy.
The Effects of Progesterone on Male Fertility and Spermatogenesis
Since progesterone (P1) is often defined as a female hormone, the importance of P1 in the male endocrine system has been largely neglected.3 Progesterone is an essential precursor of many reproductive and non-reproductive hormones in men, such as aldosterone, cortisol, and testosterone. These hormones are responsible for seemingly infinite functions in the body, including the regulation of blood pressure, sodium conservation in the kidney, the stress response, blood sugar management, sperm production, and more.1
Men produce P1 in both the testes and the adrenal glands, and their P1 levels are similar to the P1 levels present in postmenopausal women.3 In men, P1 is one of the steroid hormones that directly affects the production of sperm, a process that is known as spermatogenesis. Thus, optimal P1 production is crucial for male fertility.
Research has shown that progesterone receptors (PRs) play a significant role in the regulation of spermatogenesis in humans, and a lack of PR expression or progesterone could be an underlying cause of male infertility since progesterone acts directly via the PRs present in the testes to regulate spermatogenesis.3,5
The Relationship between Progesterone and Testosterone
A hormone called luteinizing hormone (LH) induces testosterone synthesis by the Leydig cells in the testes. In men, P1 affects the expression of the LH receptors, which must be activated by LH before the production of testosterone and other androgens will occur. According to research, many of the male-specific actions of P1 are cell membrane-dependent; therefore, supporting the health of all cellular membranes could boost male fertility and maintain optimal testosterone levels.3 Progesterone is also converted to testosterone, as shown in the image below.1
Capacitation of Sperm
Exposure to progesterone in the female genital tract plays a role in sperm capacitation and the acrosome reaction.3 Sperm must undergo capacitation and an acrosome reaction to fertilize an egg. During capacitation, numerous biochemical changes occur in the sperm for their adaptation to the shift from acidic to alkaline (basic) pH in the sperm’s external and intracellular environments as it travels along the female genital tract toward the egg.6
Capacitation leads to changes in the sperm motility pattern known as “hyperactivated movements,” which propel the sperm toward the egg and prepare the sperm for the acrosome reaction.7
The Acrosome Reaction and Fertilization
The acrosome is an anatomical structure that is located at the tip of the sperm and covers approximately 2/3 of the sperm head. The acrosome contains vesicles with numerous enzymes that are necessary for the fertilization of the egg. During fertilization, the membrane that covers the acrosome of the sperm fuses with the egg’s membrane. The acrosome reaction involves the release of acrosomal enzymes that dissolve the membranes and substances around the egg.6
Once the acrosome reaction dissolves the protective barriers around the egg, the full fusion of the sperm and egg cell - fertilization - can occur.6 Progesterone activates many of the sperm capacitation signaling pathways and stimulates the acrosome reaction; therefore, exposure to a robust amount of progesterone is required for sperm to fertilize an egg.8
The Benefits of Progesterone Beyond Fertility
In addition to the unquestionable role of progesterone in reproduction in women and men, it has numerous functions in other tissues and organs in the body, including those in the nervous, cardiovascular, musculoskeletal, immune, and gastrointestinal systems.9 Progesterone has been tested as an adjunctive treatment option for COVID-19 and is also being touted as a treatment option for pain management.3,10 These topics and more will be explored in future blog posts about progesterone.
Testing Free Progesterone Levels in Saliva
Progesterone (P1) produced in the adrenal glands and reproductive organs is released into the blood and transported throughout the body to exert biological functions. Most P1 is bound to blood proteins in the bloodstream, including cortisol-binding globulin (CBG) and albumin, while only a small proportion of the P1 remains active and unbound (free). The amount of free P1 in the blood is estimated to be approximately 2-3% of the total.2,3
Since most P1 is bound to proteins in the blood, it is best to test the free P1 levels in the saliva. Binding proteins are large and do not diffuse into the saliva; thus, the hormones in your saliva are only the free hormones actively affecting the hormone-sensitive tissues throughout your body. So, salivary hormone levels are a true, direct measurement of free, bioactive hormone levels.11
Saliva hormone testing offers many benefits, including the fact that it is non-invasive and can be collected at home. Saliva hormone testing is a clinically accurate and convenient option for testing steroid hormone levels.12-21
How to Increase Your Progesterone Level Naturally
As explained above, reproduction and life are not sustainable without adequate progesterone (P1); therefore, you might be curious about how to increase your P1 level. Before considering a protocol to boost progesterone production - test and monitor your P1 level via laboratory testing.
Ideally, menstruating females will choose to measure their P1 levels throughout an entire menstrual cycle since the P1 levels significantly change during a healthy menstrual cycle.
Once you know your salivary progesterone level, your doctor may consider a natural treatment protocol. Since progesterone is produced by the adrenal glands in both sexes, an adrenal support protocol is one option your doctor might recommend to support healthy progesterone levels and optimal fertility.
Seriphos, Magnesium3, and B-KalmPlexus support healthy adrenal function and optimal progesterone levels.*
* This statement has not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.
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- Nagy B, Szekeres-Barthó J, Kovács GL, et al. Key to Life: Physiological Role and Clinical Implications of Progesterone. Int J Mol Sci. 2021;22(20):11039. doi:10.3390/ijms222011039
- Bulletti C, Bulletti FM, Sciorio R, Guido M. Progesterone: The Key Factor of the Beginning of Life. Int J Mol Sci. 2022;23(22):14138. doi:10.3390/ijms232214138
- Kolatorova L, Vitku J, Suchopar J, et al. Progesterone: A Steroid with Wide Range of Effects in Physiology as Well as Human Medicine. Int J Mol Sci. 2022;23(14):7989. doi:10.3390/ijms23147989
- Duncan WC. The inadequate corpus luteum. Reprod Fertil. 2021;2(1):C1-C7. doi:10.1530/RAF-20-0044
- Fedotcheva TA, Fedotcheva NI, Shimanovsky NL. Progesterone as an Anti-Inflammatory Drug and Immunomodulator: New Aspects in Hormonal Regulation of the Inflammation. Biomolecules. 2022;12(9):1299. doi:10.3390/biom12091299
- He Z, Xie M, Li QQ, et al. Research Progress on the Microregulatory Mechanisms of Fertilization: A Review. In Vivo. 2022;36(5):2002-2013. doi:10.21873/invivo.12926
- Stival C, Puga Molina Ldel C, Paudel B, et al. Sperm Capacitation and Acrosome Reaction in Mammalian Sperm. Adv Anat Embryol Cell Biol. 2016;220:93-106. doi:10.1007/978-3-319-30567-7_5
- Tamburrino L, Marchiani S, Muratori M, et al. Progesterone, spermatozoa and reproduction: An updated review. Mol Cell Endocrinol. 2020;516:110952. doi:10.1016/j.mce.2020.110952
- Alqudah M, Al-Shboul O, Al Dwairi A, et al. Progesterone inhibitory role on gastrointestinal motility. Physiol Res. 2022;71(2):193-198. doi:10.33549/physiolres.934824
- Shah SB. COVID-19 and Progesterone: Part 1. SARS-CoV-2, Progesterone and its potential clinical use. Endocr Metab Sci. 2021;5:100109. doi:10.1016/j.endmts.2021.100109
- Miočević O, Cole CR, Laughlin MJ, et al. Quantitative Lateral Flow Assays for Salivary Biomarker Assessment: A Review. Front Public Health. 2017;5:133. doi:10.3389/fpubh.2017.00133
- Deneva T, Ianakiev Y, Boykinova O. Salivary mental stress biomarkers in COVID-19 patients. Front Med (Lausanne). 2022;9:999215. doi:10.3389/fmed.2022.999215
- Langelaan MLP, Kisters JMH, Oosterwerff MM, et al. Salivary cortisol in the diagnosis of adrenal insufficiency: cost efficient and patient friendly. Endocr Connect. 2018;7(4):560-566. doi:10.1530/EC-18-0085
- Tammayan M, Jantaratnotai N, Pachimsawat P. Differential responses of salivary cortisol, amylase, and chromogranin A to academic stress. PLoS One. 2021;16(8):e0256172. doi:10.1371/journal.pone.0256172
- Kobayashi H, Song C, Ikei H, et al. Diurnal Changes in Distribution Characteristics of Salivary Cortisol and Immunoglobulin A Concentrations. Int J Environ Res Public Health. 2017;14(9):987. doi:10.3390/ijerph14090987
- Bozovic D, Racic M, Ivkovic N. Salivary cortisol levels as a biological marker of stress reaction. Med Arch. 2013;67(5):374-377. doi:10.5455/medarh.2013.67.374-377
- Blair J, Adaway J, Keevil B, et al. Salivary cortisol and cortisone in the clinical setting. Curr Opin Endocrinol Diabetes Obes. 2017;24(3):161-168. doi:10.1097/MED.0000000000000328
- Raff H. Utility of salivary cortisol measurements in Cushing's syndrome and adrenal insufficiency. J Clin Endocrinol Metab. 2009;94(10):3647-3655. doi:10.1210/jc.2009-1166
- Mohamed RS, Abuelgasim B, Barker S, et al. Late-night salivary cortisol and cortisone should be the initial screening test for Cushing's syndrome. Endocr Connect. 2022;11(7):e220050. doi:10.1530/EC-22-0050
- Kim YJ, Kim JH, Hong AR, et al. Stimulated Salivary Cortisol as a Noninvasive Diagnostic Tool for Adrenal Insufficiency. Endocrinol Metab (Seoul). 2020;35(3):628-635. doi:10.3803/EnM.2020.707
- Schiffer L, Adaway JE, Baranowski ES, et al. A novel high-throughput assay for the measurement of salivary progesterone by liquid chromatography tandem mass spectrometry. Ann Clin Biochem. 2019;56(1):64-71. doi:10.1177/0004563218780904