progesterone

basic

Here you will learn the basics – explained simply and clearly.

What is progesterone?

Progesterone is a hormone produced by the body and belongs to the group of sex hormones , specifically to the progestogens (corpus luteum hormones). Based on its chemical structure, it is described as a C21 steroid hormone. ^¹ It has the molecular formula C _₂₁ H _₃₀ O _₂ and can alternatively be called pregn-4-ene-3,20-dione. ^²

Furthermore, due to its role in the central nervous system, it is also classified as a neurosteroid . ³

In synthetic form, it serves as a drug in the context of hormonal contraception ⁴ , for the treatment of gynecological problems (including menstrual disorders, conception problems and recurrent miscarriages, endometriosis) ⁵ and for hormone replacement therapy in menopause ⁶ .

What role does progesterone play in hormone or neurotransmitter metabolism?

Progesterone not only acts as a hormone itself, but is also an important precursor in the synthesis pathways of other hormones. Learn more: Which hormones or messenger substances are produced from progesterone?

Furthermore, it also influences the function of the central nervous system by modulating the effects of neurotransmitters such as glutamic acid and GABA. ⁷

Which hormones or messenger substances are produced from progesterone?

Progesterone is an important intermediate product for the synthesis of other steroid hormones:

• Androgens – in the male testes, progesterone is first converted via the Δ4 synthesis pathway to 17α-hydroxyprogesterone and then to androstenedione, from which testosterone is finally produced. ⁸
• Estrogens – in the ovaries of women, progesterone is also converted into androgens, which are then transformed into estrogens through aromatization and the removal of a methyl group. Androstenedione is converted into estrone, and this is further converted into estriol. Testosterone is converted into estradiol, which ^can then itself be converted into estrone and estriol. In men ^, some testosterone is also metabolized to estradiol.
• Cortisol – in the adrenal cortex, progesterone is converted into 17α-hydroxyprogesterone with the help of the enzyme 17α-hydroxylase. From this, the so-called stress hormone cortisol is then produced in two hydroxylation steps via the intermediate 11-deoxycortisol. ^¹¹
• Aldosterone – through double hydroxylation, 11-deoxycorticosterone is first formed, followed by corticosterone, which is then converted to aldosterone by oxidation of the methyl group. ¹²

Which natural sources contain progesterone?

Progesterone can be detected in numerous plants (including rice, corn, and beans) ¹³ and also in high-fat dairy products such as butter, cream, and cheese. However, compared to the body's own production, these are very small amounts, which our bodies cannot simply "use" but largely break down via the liver and kidneys. ¹⁴

Those seeking natural sources of progesterone are referred by alternative medicine practitioners to so-called phytohormones and to natural or bioidentical hormones. Phytohormones are plant compounds that trigger hormone-like effects in the human body. However, compared to phytoestrogens, there are currently only a few studies on phytoprogestins . ^¹⁵

Natural or bioidentical hormones (also: bioidentical hormones, BIH, or nature-identical hormones) have the same chemical and molecular structure as the hormones produced by the human body. ^¹⁶ They are manufactured in the laboratory using diosgenin, which is derived from wild yam or soy and can serve as a precursor for, among other things , natural progesterone . ^¹⁷

What processes in the body are associated with progesterone?

• Menstrual cycle & pregnancy : increased production after ovulation to prepare the uterine lining for implantation of the egg, accompanied by a slight increase in body temperature; if pregnancy occurs, the hormone supports its maintenance, alters the tone of the uterine muscles (myometrium), the consistency of cervical mucus, and the development of the mammary glands. ¹⁸
• Promotion of sperm motility and acrosome reaction ¹⁹ , i.e. sperm motility and enzyme secretion that enables the fusion of sperm and egg cell.
• Function of the central nervous system : modulates the effect of neurotransmitters such as glutamic acid, aspartic acid, and GABA; this can affect mood and well-being in some individuals and may also influence the effects of neuropharmaceuticals, as well as the effects of stress on the psyche and potentially the immune system. ²⁰
• Intermediate product in hormone synthesis ; more information: Which hormones or messenger substances are produced from progesterone?

Furthermore, progesterone also affects the cardiovascular system ²¹ , gastrointestinal function (including reduced intestinal motility) ²² , and bone density ^23. From a therapeutic point of view, the neuroprotective effects of the hormone also appear to be very interesting. ²⁴

How is progesterone produced and replenished in the body? What are possible causes for reduced progesterone synthesis?

Our bodies can produce the sex hormone themselves: Synthesis occurs primarily in the gonads – that is, in the corpus luteum of the ovaries and in the testes, and to a lesser extent in the adrenal cortex, and, if pregnancy occurs ^, also in the ^placenta . Small amounts are also produced in the glial cells of the central nervous system.

Reduced progesterone synthesis in women requires extensive diagnostic evaluation: Possible causes include both congenital and acquired ovarian dysfunction, e.g., due to trauma or inflammation of the ovaries, disorders of the hypothalamic-pituitary axis (see: How is progesterone produced and regulated in the body? ), thyroid dysfunction (since thyroid and sex hormones interact ⁾ , or hyperandrogenemia (increased androgen production in women, especially PCOS). A specific condition characterized by insufficient progesterone synthesis is corpus luteum insufficiency, also ^known as luteal phase deficiency, which is characterized by insufficient progesterone levels during the luteal phase and/or a shortened duration of this phase.

Obesity can also cause both dysregulation of the hypothalamic-pituitary-ovarian axis and impairment of hormone synthesis in the ovary itself. ²⁹

For information on the influence of stress, sleep, and exercise, see: Which lifestyle factors are associated with progesterone metabolism?

How is progesterone regulated or broken down in the body? What physiological mechanisms ensure a balance of progesterone?

Progesterone levels are regulated by hormonal signals along the hypothalamic-pituitary-gonadal axis. Learn more: How is progesterone produced and regulated in the body?

Progesterone is broken down via the liver and kidneys; see: How is progesterone converted and broken down in the body?

Advanced

This section will deepen your knowledge and give you more detailed insights.

How is progesterone produced and regulated in the body?

The starting materials for the synthesis of this sex hormone are cholesterol and the pregnenolone derived from it. You can learn more about this process here: Which biochemical precursors and enzymes are involved in the synthesis of progesterone?

The hypothalamus in the brain triggers the start signal for progesterone synthesis in the gonads: The release of gonadotropin-releasing hormone ( ^GnRH ) stimulates the pituitary gland to produce gonadotropins (follicle-stimulating hormone, or FSH, and luteinizing hormone, or LH). These gonadotropins then stimulate the production of sex hormones in the gonads, the sex glands.

A high progesterone level then acts as a feedback signal that reduces the release of GnRH in the hypothalamus and also suppresses the release of luteinizing hormone (LH) in the pituitary gland. ³¹

Which foods contain precursors of progesterone?

The main precursor substances are cholesterol and pregnenolone (for more details, see: Which biochemical precursors and enzymes are involved in the synthesis of progesterone? ).

• Cholesterol is found exclusively in foods of animal origin, primarily in high-fat dairy products, egg yolks, fish, and meat (especially in the brain, kidneys, and liver). ³²
• Although pregnenolone can be detected in some plants (e.g. wheat ³³ ), a physiologically effective intake is not possible through a simple diet.

Which lifestyle factors are associated with progesterone metabolism?

The effect of stress on hormone synthesis is complex and, in women, is also influenced by the menstrual cycle. In the first half of the cycle (follicular phase), stress causes progesterone levels to rise, and an interaction with the "stress hormone" cortisol can also be observed here. ³⁴ In the luteal phase, however, stress appears to be associated with lower progesterone levels. ³⁵

Numerous studies demonstrate the importance of progesterone for falling asleep and undisturbed sleep, particularly uninterrupted breathing during sleep. Conversely, the influence of sleep on progesterone synthesis has so far been insufficiently researched – however, a prospective study with 259 female participants suggests a positive relationship between sleep duration and mean progesterone levels in the luteal phase. ³⁶

A significant effect of physical activity does not appear to be demonstrable. ³⁷ However, individual studies point to noticeable effects in the context of certain gynecological diagnoses, e.g., a reduction in premenstrual syndrome ³⁸ or an increase in the late luteal phase in primary dysmenorrhea ³⁹ .

Short periods of fasting can slightly increase progesterone levels, while reducing its conversion to other steroid hormones. ⁴⁰

How does the concentration of progesterone change with age or life stages?

In the fetus, serum levels are similar to those in the mother. During childhood, hormone secretion (especially gonadotropins) is then very low and uniform. ⁴¹

With the onset of puberty, the production of sex hormones increases. In men, the serum progesterone level is 0.3–1.2 μg/L, which is generally lower than in women. In women, the level is subject to considerable fluctuations.

• cyclical fluctuation, with serum levels of < 1 μg/L in the first half of the cycle (follicular phase) and ≥ 8 μg/L in the second half of the cycle (luteal phase) after ovulation.
• A sharp increase occurs during the course of pregnancy, from 10-50 μg/L in the 1st trimester to 20-130 μg/L in the 2nd trimester and up to 130-420 μg/L in the 3rd trimester.
• Postmenopausal decline in hormone production to values ​​of < 1 μg/L

The measured values ​​may vary depending on the method used; therefore, the information provided should only be understood as a guideline. ⁴²

What myths and misconceptions surround progesterone?

• “ Progesterone is only a female hormone ” – yes and no! Men also produce progesterone, not just as an intermediate step on the way to testosterone, but as a sex hormone with an important function in fertility. ⁴³ More on this: Which processes in the body are associated with progesterone?
• “ Progesterone makes you slim ” or conversely, “ Progesterone makes you fat ”—the very contradictory nature of the reports circulating online and offline suggests that the facts are, at best, ambiguous. In fact, progesterone does have various effects on metabolism, but these are primarily relevant in the context of pregnancy. ^⁴⁴ The widespread fear that progesterone causes weight gain in the context of estrogen-free contraceptives is refuted in most studies. ^⁴⁵ On the other hand, progesterone replacement therapy in postmenopausal women appears to support the reduction of body fat. ^⁴⁶
• “Premenstrual syndrome ( PMS) is caused by a low or falling progesterone level ” – yes and no! The temporal correlation between PMS symptoms and declining hormone levels is undeniable, but serum levels show no significant differences between those with and without PMS. Rather, an increased sensitivity to hormone fluctuations appears to be crucial, particularly for allopregnanolone, a progesterone derivative that modulates the activity of GABA receptors in the central nervous system. Furthermore, reduced serotonin availability also seems to play a role in the development of PMS. ^⁴⁷

Expert

This section deals with advanced concepts for a deeper understanding.

Which biochemical precursors and enzymes are involved in the synthesis of progesterone?

The starting material for the formation of all steroid hormones is cholesterol . This is first converted to pregnenolone in the mitochondria of cells through hydroxylation. The enzyme cholesterol desmolase (also known as cholesterol monooxygenase), which belongs to the cytochrome P450 enzyme family, acts as a catalyst in this process. The pregnenolone then enters the cytoplasm and is converted to progesterone by another enzyme, 3β-hydroxy dehydrogenase (also known as 3β-hydroxysteroid dehydrogenase). ⁴⁸

How is progesterone converted and broken down in the body?

In women, approximately 15-30% of the progesterone produced daily is converted into breakdown products and excreted. ^⁴⁹ The liver and kidneys are responsible for this process. ^⁵⁰

For information on the conversion to other hormones, see: Which hormones or messenger substances are produced from progesterone?

Which enzymes and other substances are involved in the conversion or breakdown of progesterone?

The breakdown of progesterone produces hydroxylated pregnanes, especially pregnanediol . These are then bound to glucuronic acid (glucuronidation) and excreted in the urine. ⁵¹

The enzymes 5β-reductase and 3α-hydroxysteroid dehydrogenase are involved in the conversion of progesterone to pregnanediol. A second conversion pathway, involving the enzyme 17α-hydroxylase, leads via the intermediate 17α-hydroxyprogesterone to pregnanttriol, another progesterone degradation product. ⁵²

Alternative medicine practitioners also refer to the so-called " pregnenolone steal ": According to this theory, increased production of cortisol and other stress hormones reduces the amount of pregnenolone available for progesterone synthesis. After all, cortisol synthesis relies on the same precursors, particularly pregnenolone, that are also involved in progesterone synthesis (see: Which biochemical precursors and enzymes are involved in the synthesis of progesterone? ). ^⁵³ However, this concept is controversial and not recognized by conventional medicine. It is emphasized, in particular, that the production of steroid hormones does not draw from a common "pregnenolone pool," but is distributed across different layers of the adrenal cortex, and that there is no exchange between the pregnenolone stores in the mitochondria of different tissue cells. ^⁵⁴

The interaction between progesterone and the “sleep hormone” melatonin is also the subject of current research. ⁵⁵

What physiological conditions influence the concentration of progesterone?

Progesterone levels are influenced by age and sex. In adult women, the level is also affected by the menstrual cycle phase, pregnancy, and the onset of menopause. ⁵⁶

Illnesses, as well as nutritional and environmental factors, can also affect hormone levels. Learn more: How is progesterone produced and replenished in the body? What are possible causes of reduced progesterone synthesis?

Furthermore, some studies point to circadian rhythms, meaning that the time of day also controls the serum concentration of the hormone. ⁵⁷

Scientific sources