Inhibin is an important hormone for male and female reproductive health. It is involved in the development of reproductive organs, fertility, and pregnancy. It also serves as a diagnostic marker for a variety of body functions and conditions. Read on to learn more about the roles of inhibin, normal blood levels, and conditions associated with high and low levels of this hormone.
What Is Inhibin?
Inhibin is a hormone secreted in response to FSH [1].
In turn, inhibin ultimately suppresses the production and release of FSH from the pituitary gland [2].
Inhibin plays an important role in male and female reproductive development [3, 4, 5].
Reproductive organs are the main source of inhibin, although it can also be found in the prostate, brain, and adrenal glands [6].
Activin is another sex hormone that increases FSH and gonadotropin-releasing hormone (GnRH) production. Inhibins suppress this increase in FSH and GnRH by blocking the binding of activin to its receptors [7].
There are two forms of inhibin, inhibin A and B [8].
Inhibin A and B
Inhibins are protein complexes with two units linked to each other. These are called inhibin A and B [8].
Blood inhibin A and B levels vary throughout the menstrual cycle. Inhibin A levels are highest during the late follicular and luteal phases of a normal menstrual cycle, whereas inhibin B dominates in the early and mid follicular phases and declines in the late follicular phase [9, 10].
During the late luteal phase, inhibin A levels drop, allowing FSH levels to increase. This activity plays a role in the biological changes within a menstrual cycle [11, 12].
In contrast, males only produce inhibin B, which is produced in the testis by the Sertoli cells. Inhibin B production and secretion changes during the development of testis, and inhibin B increases or decreases the secretion of FSH depending on the sperm production process [13].
Production
FSH stimulates the production of inhibin by the granulosa cells of the ovaries and the Sertoli cells of the testes [14].
Other factors that increase inhibin production include:
Factors that reduce inhibin production include:
- Progesterone [14]
- IL-1 (for inhibin B) [17]
In females, inhibin secretion increases as the follicle matures. This enhances the activity of aromatase, the enzyme involved in the production of estrogen [14].
Roles of Inhibin
1) Maintains Male Reproductive Function
Inhibin B, which is produced in the testis by the Sertoli cells, is the active form of inhibin in men. As blood inhibin B levels increase, FSH levels decrease. Higher blood levels of inhibin B increase the number of Sertoli cells and sperm production in healthy fertile males [18, 8].
Sperm Production
Inhibin B is a marker of sperm production and male reproductive health. Blood inhibin levels were reduced in 104 men with various testicular disorders as compared to normal men [19, 20].
In a study with nearly 1,800 fertile men, elevated blood inhibin B levels were associated with increased sperm count and concentration [21].
2) Supports Female Reproductive Function
In women, inhibins A and B have a different pattern of secretion throughout the menstrual cycle [22].
Decreased inhibin B secretion decreases the ovarian follicular pool in women and leads to infertility [23].
Also, inhibin levels during pregnancy are higher than those during a normal menstrual cycle [24].
Because inhibins are produced by the placenta and fetal membranes, they may be used to diagnose fertility problems and early pregnancy [22].
A mutation in inhibin gene is associated with premature ovarian failure (POF). This causes a reduction in inhibin B activity, and thus, inhibin B levels are used to detect POF and ovarian recovery in women with hypothalamus-associated problems [25, 26].
Additionally, both inhibin A and B can be used to assess the function of the ovaries in patients with Turner syndrome, a genetic disorder [26].
Total inhibin levels in the blood are also used in the diagnosis of patients with polycystic ovary syndrome (PCOS) and ovarian tumors [26].
Ovarian Health
Ovarian reserve is the ability of the ovaries to produce egg cells capable of fertilization for a successful pregnancy. Decreased inhibin B levels were seen in women with declining ovarian reserve [27, 28].
Women with low blood inhibin B levels also showed a reduced response to ovulation stimulation and a decreased chance of becoming pregnant, naturally or with assisted reproduction [29].
Inhibins enhance the health and development of ovarian follicles. Higher levels of inhibin A and B in the follicular fluid also increase pregnancy rates [30].
3) Impact Bone Formation
The bone activity of removal and replacement of bone takes place throughout the body. Bone mass is maintained by a balance of bone formation and bone loss. Inhibin suppressed both of these activities in mice bone marrow [31, 32].
Studies in menopausal women showed that increased inhibin B levels correlated with lower bone density [33].
Low blood inhibin levels were associated with increased markers of bone formation and bone loss in pre- and perimenopausal women [34].
However, in mice, high levels of inhibin A increased bone mass and strength [35].
4) May Be Involved in Eye Development
In the developing mouse eye, inhibin was seen in the lens and the cells between the lens and optic disc. It was also found in various cell layers of the retina. These results suggest that inhibin may be involved in the development of the retina [36].
Similarly, in the adult rat eye, a subunit of inhibin (α-subunit) was detected in cells of the retina that respond to light [37].
5) May Reduce Blood Cell Production
Inhibins reduce human blood cell production by suppressing the activity of human bone marrow cells [38].
Decreased production of bone marrow and splenic cells was seen after inhibin injection (in the vein) in mice [39].
Conditions Associated with Low Inhibin Levels
Inhibin levels are a marker of reproductive health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.
1) Ectopic Pregnancy
An ectopic pregnancy occurs when the fertilized egg attaches itself to sites other than the uterus. Reduced maternal blood inhibin levels were seen in ectopic pregnancies compared to normal pregnancies [40].
Similarly, another study found lower blood inhibin A levels in patients with ectopic pregnancies and abnormal pregnancies involving miscarriage. These results indicate that inhibin levels may be used as a marker for the ectopic or abnormal pregnancies [41].
2) Menopause
During menopause, ovarian follicles, inhibin, estrogen, and androgen levels are reduced while FSH levels increase. As a result of these changes, the menstrual cycle becomes irregular [42, 43].
In women over 40 years with periods, high levels of FSH were only linked to reduced blood inhibin B levels but not inhibin A levels [44].
The luteal phase is also affected by age. In older women, during this phase, progesterone levels remain stable but inhibin A levels are reduced [43].
3) Premature Ovarian Failure (POF)
POF is a condition associated with loss of menstruation, infertility, and increased sex hormone levels in women under the age of 40. In these women, blood inhibin A and B levels are lower, while FSH is higher [45, 46].
4) Male Infertility
Inhibin B is important for Sertoli cell development and sperm production [47].
Low levels of inhibin B reduce sperm production and can lead to testicular problems. Thus, inhibin B levels may be useful in predicting male infertility [48].
In a clinical study of 160 males, blood inhibin B levels were used as a marker for male infertility [49].
5) Pregnancy Loss
Blood inhibin A levels increase over the course of pregnancy. They remain low during the first and second trimesters and then rise during the third trimester [50].
In the later stages of pregnancy, the fetal placenta becomes the major source of inhibin. In a spontaneous abortion study, a significant decrease in maternal blood inhibin A levels was observed [51].
Thus, inhibin A may be useful in predicting spontaneous abortion and early pregnancy loss.
Inhibin A may also predict the survival of the fetus during early pregnancy in women undergoing in vitro fertilization (IVF). Increased pregnancy loss was seen in women with lower blood inhibin A after IVF [52, 53].
Conditions Associated with High Inhibin Levels
Inhibin levels are a marker of reproductive health. Low or high levels don’t necessarily indicate a problem if there are no symptoms or if your doctor tells you not to worry about it.
1) Ovarian Cancer
Ovarian cancer is one of the most common cancers in women, and inhibins play a role in its development [54, 55].
Inhibin B is the major form of inhibin secreted by granulosa cell tumors and can be used as a tumor marker to determine response to therapy [56].
Total inhibin levels were elevated in six postmenopausal women with granulosa cell tumors [57].
Blood levels of inhibins were raised in women with mucin-producing epithelial cell cancers [58].
2) Breast Cancer
Blood inhibin also increases significantly in breast cancer [59].
Women with breast cancer that underwent surgery showed a decrease in blood inhibin levels, indicating that these tumors may be secreting inhibins [60].
Inhibins can be also be used as a marker to diagnose breast cancer in postmenopausal women. In these women, inhibin levels were already very low, thus any changes in inhibin levels were useful in the detection of a tumor [61].
3) Down Syndrome
The risk of having a child with Down syndrome is highest among women over 35 years of age [62].
The link between increased blood inhibin and Down syndrome was seen in various studies [63, 64].
Inhibin A is used in tests performed to predict the risk of Down syndrome [65].
4) Preeclampsia
Preeclampsia is a complication of pregnancy that causes high blood pressure and organ damage after 20 weeks of pregnancy. Inhibin is a marker for the detection of preeclampsia [66].
Blood inhibin A levels were increased in women with preeclampsia compared to those with a normal pregnancy [67].
Elevated maternal inhibin A levels are also associated with increased severity of preeclampsia [68].
Blood Levels of Inhibin
Normal
In men
Inhibin A levels: < 2 pg/ml
Inhibin B levels: 138 pg/mL [69]
In women
Inhibin A levels: Premenopausal women 2-80 pg/ml; Postmenopausal women is < 5 pg/ml [70]
Inhibin B levels: Premenopausal women <200 pg/ml; Postmenopausal women is < 15 pg/ml [71]
In pregnant women
Inhibin A: 1.8- 2.31 ng/mL (week 8); 2 ng/mL (weeks 8-24); 24-30 ng/mL by (week 38) [72]
Inhibin B: <12 pg/ml (week 5-16); 19-31 pg/ml (week 36) [73]
*Because inhibin levels vary throughout the menstrual cycle, inhibin levels in premenopausal women should be interpreted carefully.
Factors That Decrease Inhibin
- Progesterone [14]
- IL-1 (for inhibin B) [17]
Factors that Increase Inhibin
Treatments
- Varicocele Treatment: Varicocele (varicose veins on the scrotum) treatment increased blood inhibin b levels in infertile men [74].
- Human chorionic gonadotropin (hCG) treatment: HCG treatment in healthy men significantly increased blood inhibin levels [75].
Lifestyle Factors
- Losing weight: Inhibin B levels decrease with increasing weight in males and females [76, 77].
- Smoking cessation: Smoking history was negatively correlated with inhibin B levels in older reproductive-aged women [78].
