Low level of progesterone refers to serum progesterone concentration below the lower limit of the reference range (Pic. 1) for a given age group and, in fertile women, for the specific phase of the ovarian cycle (Pic. 2). Progesterone is naturally low in prepubescent girls and in postmenopausal women. In fertile women, its concentration varies greatly depending on the phase of ovarian cycle. After the woman ovulates, the newly formed corpus luteum starts producing large quantities of progesterone, and the serum progesterone concentration almost doubles. This induces the effects that are typical for the luteal phase of the ovarian cycle. If the serum progesterone is low during the luteal phase, the phase itself is shorter than usual, or both, the condition is called luteal phase defect.

The main physiological roles of progesterone are as follows:

  • to induce the secretory phase of the uterine cycle (Pic. 3), making the endometrium (uterine cavity lining) capable of supporting embryo implantation
  • to maintain the endometrium during the first weeks of pregnancy
  • to induce changes of the endometrial glands

When the corpus luteum fails to produce sufficient amount of progesterone, the endometrium doesn’t undergo the secretory changes in the secretory phase, and is not capable of supporting the implantation of an embryo. This in turn results in infertility or in recurrent pregnancy loss.


Low levels of progesterone are seen in conditions of hypogonadism, with a failure of the ovary to produce the sex hormones estrogen and progesterone. Hypogonadism may be caused either by insufficient hormonal stimulation of the ovary from the superior centres, the pituitary and the hypothalamus (so-called hypogonadotropic hypogonadism), or by a disorder of the ovary itself – such as destruction of the ovary due to trauma, ovarian torsion, infection or poisoning (so-called hypergonadotropic hypogonadism). However, in hypogonadism, there is low level of estrogen as well.

Low level of progesterone and/or luteal phase defect is also associated with diseases such as polycystic ovary syndrome (PCOS), luteinized unruptured follicle syndrome (LUFS) and endometriosis.

Symptoms

Progesterone deficiency most notably causes menstrual irregularities and anovulation. Because estrogen may become the dominant hormone, the woman may also experience heavy menstrual bleeding with cramping, breast tenderness or weight gain. Progesterone deficiency brought on by menopause is also associated with other menopause symptoms, such as fatigue, hot flashes, mood swings, vaginal dryness, lower sexual desire and depression.

Associated diseases

Polycystic ovary syndrome (PCOS)

Polycystic ovary syndrome is a condition in which a woman has an imbalance of female sex hormones and cysts in the ovaries. PCOS is the most common cause of menstrual disturbance such as oligomenorrhea (infrequent or very light menstruation), anovulation (the condition of no eggs being released from the ovary), menorrhagia (excessively heavy menstrual flow), and infertility. The level of progesterone is decreased in PCOS which cannot suppress LH (luteinizing hormone) pulse frequency in PCOS; therefore, increased estrogen secretion may contribute to the aforementioned complications. Polycystic ovary syndrome causes more than 75% of cases of anovulatory infertility. Not all women with PCOS have difficulty becoming pregnant. For those who do, anovulation is a common cause. 

Luteinized unruptured follicle syndrome

LUFS stands for the luteinisation (changes typical for the luteal phase of the ovarian cycle) of ovulatory follicle without releasing an oocyte. Therefore, it can be considered as a form of anovulation. As it is a disorder united with the start of so-called luteal phase, it may be also characterized as luteal phase defect. It seems that LUFS is related to hormonal imbalance causing the detention of oocyte within the follicle even though the follicle itself transforms under LH (luteinizing hormone) influence into corpus luteum. The oocyte detention prohibits the conception, yet menstrual cycle is in any other aspect undergoing normally without any side effects. Regarding the importance of progesterone and its role in the ovulation, it is reasonable to assume that its lowered levels may be responsible for LUF to happen.

Endometriosis

Endometriosis is a condition in which pieces of the endometrium grow outside the uterine cavity, such as in the muscular portion of the uterine wall or in the surrounding organs. About 40% of women with endometriosis are infertile. Low levels of progesterone are associated with endometriosis, and may contribute to its detrimental effect on fertility.

Complications

Infertility

Low levels of progesterone mean that the endometrium does not undergo the secretory changes necessary for the implantation of an embryo and its early development. Also, the hormonal imbalance may lead to an anovulatory state. Therefore, a woman suffering from decreased progesterone and/or luteal phase defect may experience difficulty conceiving or recurrent pregnancy loss, and as a consequence, infertility.

Risk factors
  • hypogonadism
  • menopause
  • endometriosis
  • hyperestrogenism (elevated estrogen level) 
  • polycystic ovary syndrome
  • stress
Prevention

Apart from conditions of hypogonadism and luteal phase defect, low progesterone levels, especially in younger women, are also associated with stress and anxiety. Maintaining a healthy lifestyle and avoiding too much stress can therefore help to prevent progesterone deficiency. Furthermore, consumption of exogenous estrogen (such as in hormonal replacement therapy) can lead to hyperestrogenism, supressing the production of the body’s own progesterone through the negative feedback mechanism. Avoiding consumption of exogenous estrogen sources helps to prevent the decrease in progesterone induced by hyperestrogenism. 

Progesterone is essential for the luteal phase of the menstrual cycle, for the implantation of an embryo and for the function of the uterus during pregnancy. Low progesterone causes distrubances in these processes and may lead to severely impaired fertility.

In nonpregnant women, low levels of progesterone may lead to irregular or absent periods and abnormal uterine bleeding. They may also experience mood swings, depression and low sex drive. Progesterone is necessary for the changes of the endometrium during the luteal phase, including the thickening of the endometrium and growth and activity of the endometrial glands. These changes are necessary for the succesful implantation of the fertilized egg, and therefore for the initial stage of pregnancy. Without these changes in the endometrium, the fertilized egg will not be able to implant, and pregnancy will not occur. 

Because progesterone is produced by the ovary (more specifically, by corpus luteum, which is contained within the ovary), its levels can be low in various conditions of hypogonadism (decreased secretion of sex hormones by the gonad). In hypogonadism, the levels of estrogen are usually low as well. Hypogonadism has many causes, both congenital and acquired. Women suffering from hypogonadism are infertile, or have significantly reduced fertility.

Low progesterone can also cause miscarriage in pregnancy. Initially, progesterone produced by the corpus luteum is necessary for maintaining the function of uterus. After 8-10 weeks of pregnancy, the progesterone production is largely taken over by the placenta. Low progesterone production by the corpus luteum can cause an unviable pregnancy and death of the embryo. If symptoms of low progesterone are present, the patient should undergo blood test for the level of progesterone and a gynaecologic examination.

 Low level of progesterone may lead to many different problems, including lower fertility and various symptoms affecting the quality of life. However, there are several types of treatment that women with low progesterone may benefit from. The administration of hormones, called hormone therapy, utilizes administration of exogenous progesterone in various forms. This treatment may be the sustainable solution for perimenopausal (approaching menopause or shortly after menopause) and postmenopausal women. 

Several hormones including progesterone may be also administered to support the function of the corpus luteum and increase the chance of implantation. This is termed luteal support, and it may increase the pregnancy rate and live birth rate in women undergoing IVF (in vitro fertilization) procedure.

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Sources

“POLYCYSTIC OVARY SYNDROME” ―sourced from Fertilitypedia.org licensed under CC BY-SA 4.0
“Polycystic Ovary Syndrome May Be an Autoimmune Disorder” ―by Mobeen et al. licensed under CC BY 4.0
“Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome” ―by Meenakumari et al. licensed under CC BY 4.0
“LUTEINISED UNRUPTURED FOLLICLE SYNDROME” ―sourced from Fertilitypedia licensed under CC BY-SA 4.0
“Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome” ―by Huang et al. licensed under CC BY 4.0
“The high concentration of progesterone is harmful for endometrial receptivity and decidualization” ―by Liang et al. licensed under CC BY 4.0
“Progesterone reference range” ―by Urban, created for Fertilitypedia.org licensed under CC BY-SA 4.0
“Menstrual cycle” ―by CNX OpenStax licensed under CC BY 4.0
“Uterine cycle” ―by Smallbot licensed under CC BY 3.0
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