Follicle-Stimulating Hormone

Understanding the intricate hormonal mechanisms governing reproductive health is paramount in both diagnosis and treatment of many conditions.  Follicle-Stimulating Hormone (FSH) is an essential hormone for female and male reproductive health. 

In women, it helps the growth and development of ovarian follicles, each containing a potential egg for fertilization. In men, FSH supports sperm production. 

This article aims to provide a comprehensive overview of FSH by exploring its functions, production, testing methods, and clinical implications. We’ll begin with an exploration of what FSH is, where and how it’s produced, and that cells and tissues it acts on.   

Additionally, we discuss the significance of FSH testing, including when and why it is conducted. Finally, we examine the potential repercussions of inhibited FSH levels on fertility and reproductive health. 

What is Follicle Stimulating Hormone?

Definition of Follicle Stimulating Hormone (FSH)

Follicle Stimulating Hormone (FSH) is a vital glycoprotein hormone produced by the anterior pituitary gland, a pea-sized structure in the brain. As one of the gonadotropins, FSH plays a pivotal role in regulating reproductive processes in both males and females.  [15.]

Its name derives from its primary function in females, where it stimulates the growth and development of ovarian follicles, which house the maturing eggs (oocytes) within the ovaries.

Role of FSH in the Body

In both sexes, FSH serves as a key regulator of reproductive function, exerting its effects through specific receptors located on the surface of target cells. 

Role of FSH in Women

In females, FSH promotes follicular development in the ovaries during the menstrual cycle, stimulating the growth of ovarian follicles and supporting the maturation of oocytes. Additionally, FSH plays a crucial role in initiating the production of estrogen by the ovarian follicles. 

In women, the release of follicle-stimulating hormone (FSH) from the pituitary gland is primarily stimulated by gonadotropin-releasing hormone (GnRH) secreted by the hypothalamus in a pulsatile manner.  FSH is a major director of the follicular phase of the menstrual cycle.

FSH is critical for ovulation and reproduction because it ensures the maturation of ovarian follicles and the release of a mature egg during each menstrual cycle. In perimenopause, FSH levels tend to rise as ovarian function declines, leading to irregular menstrual cycles and eventually menopause. This increase in FSH reflects the decreased ovarian reserve and declining fertility characteristic of the perimenopausal transition.

Role of FSH in Men

In males, FSH acts on the Sertoli cells within the testes, stimulating spermatogenesis, the process of sperm cell production. Specifically, FSH seems to play a role in both the initiation and maintenance of spermatogenesis, as well as in directing sperm quantity and quality.  [14.]  

Production and Secretion of FSH

Gland Responsible for FSH Secretion

The production and secretion of FSH are primarily regulated by the relationship between the hypothalamus and the anterior pituitary gland, both located in the brain.  

Within the anterior pituitary, specialized cells called gonadotrophs are responsible for synthesizing and releasing FSH in response to complex hormonal signals from the hypothalamus. 

The hypothalamus secretes gonadotropin-releasing hormone (GnRH), which acts on the gonadotrophs to stimulate the synthesis and release of FSH, along with luteinizing hormone (LH).    

Once released into the bloodstream, FSH travels to the ovaries in females and the testes in males, where it exerts its diverse effects on reproductive function.

Regulation of FSH Release

The secretion of FSH is tightly regulated by a delicate interplay of hormonal signals from the hypothalamus and feedback mechanisms involving sex steroids, particularly estrogen and testosterone. 

Gonadotropin-releasing hormone (GnRH) is responsible for stimulating the release of follicle-stimulating hormone (FSH) from the anterior pituitary. Produced by the hypothalamus, GnRH enters the hypophyseal portal circulation and binds to gonadotropic cells in the anterior pituitary, prompting the production and secretion of both FSH and luteinizing hormone (LH) into the bloodstream. 

GnRH release is pulsatile, where low frequencies of pulses primarily stimulate FSH production, while higher frequencies prompt more LH production. Continuous administration of GnRH, as seen with GnRH agonists like leuprolide, can suppress the release of FSH and LH, consequently inhibiting ovulation and estrogen production in women. 

During the follicular phase of the menstrual cycle, follicle-stimulating hormone (FSH) plays a crucial role in fostering the maturation of ovarian follicles. As a single dominant follicle emerges and begins secreting estradiol and inhibin, FSH secretion is suppressed. 

Once the dominant follicle achieves a threshold level of estradiol, typically maintaining levels of 200 to 300 pg/ml for 48 hours, the hypothalamus initiates a surge of gonadotropin-releasing hormone (GnRH), which in turn stimulates the secretion of gonadotropic hormones instead of inhibiting them. This surge leads to a peak in both FSH and luteinizing hormone (LH), coinciding with the LH surge that precipitates ovulation. [2.]

Following ovulation, FSH levels diminish significantly during the luteal phase, thereby preventing the development of new follicles.

While in females, negative feedback from estrogen levels hampers FSH secretion, in males, inhibin B, secreted by Sertoli cells in response to FSH, inhibits FSH secretion through negative feedback mechanisms.

Target Cells for FSH

Ovarian Target Cells for FSH

FSH acts on the granulosa cells of the ovarian follicles to promote their maturation. Specifically, FSH stimulates the follicles to produce estrogen by upregulating the enzyme aromatase.  Increased estrogen during the follicular phase stimulates follicle development, preparing the body for ovulation. [15.]

Additionally, FSH promotes the proliferation of granulosa cells and the development of follicles, ultimately contributing to the selection of a dominant follicle for ovulation.

Testicular Target Cells for FSH

FSH primarily targets the Sertoli cells within the testes, where it plays a crucial role in spermatogenesis, the process of sperm cell development.

Within the seminiferous tubules, FSH stimulates Sertoli cells to support germ cell maturation and provide essential nutrients and growth factors necessary for sperm production. 

Additionally, FSH promotes the synthesis of androgen-binding proteins by Sertoli cells, facilitating the delivery of testosterone to developing sperm cells and supporting their maturation within the testicular environment.

Testing for FSH

Clinical Relevance of FSH Testing

Testing for follicle-stimulating hormone (FSH) is vital for assessing various reproductive and endocrine conditions. 

In cases of infertility, FSH testing serves as a fundamental diagnostic tool to evaluate ovarian function and the responsiveness of the ovaries to hormonal stimulation. Elevated FSH levels may indicate diminished ovarian reserve, a common cause of infertility, while abnormally low levels could suggest hypothalamic or pituitary dysfunction. 

Additionally, FSH testing is crucial during perimenopause, the transitional phase preceding menopause, to monitor hormonal changes associated with declining ovarian function. 

During perimenopause, FSH levels typically rise as the ovaries produce fewer follicles and become less responsive to hormonal signals, leading to irregular menstrual cycles and eventual cessation of menstruation.

What is the FSH Test?

The FSH test, also known as the FSH blood test, measures the concentration of follicle-stimulating hormone in the bloodstream. This test involves collecting a blood sample, usually from a vein in the arm, and analyzing it to determine the level of FSH present. 

Many labs offer FSH testing as a blood spot test, allowing for up to daily sampling to track menstrual cycle changes from the comfort and convenience of home.  [5.]

When is the FSH Test Performed?

FSH testing is typically conducted at specific times during a woman's menstrual cycle to assess ovarian function and reproductive health accurately. In women with regular menstrual cycles, FSH levels are typically measured on the third day of the menstrual cycle, known as cycle day 3. 

However, for women with irregular menstrual cycles or amenorrhea, FSH testing may be performed at any time to evaluate ovarian function and diagnose potential reproductive disorders.

Normal Ranges for FSH

Typical ranges for FSH levels vary across the lifespan and between males and females.  It is important to note that different labs may use different reference ranges.  

Typical ranges include:  [6., 16.]

Normal findings for FSH (IU/L)

Adults:

Male: 1.42-15.4

Female:

Follicular phase: 1.37-9.9

Ovulatory peak: 6.17-17.2

Luteal phase: 1.09-9.2

Postmenopause: 19.3-100.6

Child (1-10 years):

Male: 0.3-4.6

Female: 0.68-6.7

Causes of Altered FSH Levels

Pituitary Adenomas

• Pituitary adenomas can secrete excess FSH and/or LH, causing ovarian hyperstimulation and hormonal imbalance.

Male Infertility

• Elevated FSH levels indicate Klinefelter syndrome if accompanied by small, firm testes and azoospermia or oligospermia, while normal testicular size with azoospermia or oligospermia suggests primary impairment of spermatogenesis.
• FSH levels remain normal in obstructive infertility, whereas primary spermatogenic impairment leads to elevated FSH levels.
• FSH preparations are used in treating secondary hypogonadism in males to induce spermatogenesis and enhance fertility.

Polycystic Ovarian Syndrome (PCOS)

• PCOS is characterized by elevated androgens, anovulation, and polycystic ovaries, often presenting with hirsutism, obesity, insulin resistance, menstrual irregularity, and infertility.
• In PCOS, persistently rapid GnRH pulses lead to increased LH:FSH ratio, resulting in excess androgen production by the theca cells due to insufficient aromatase activity in granulosa cells.

Hypogonadotropic Hypogonadism

• Low FSH and LH levels in amenorrhea indicate hypothalamic or pituitary dysfunction.
• Stress-induced hypogonadotropic hypogonadism results from decreased GnRH pulse frequency and amplitude due to physiological stress, leading to low FSH and LH levels, often seen in athletes and individuals with eating disorders.

Kallman Syndrome

• Anosmia and hypogonadotropic hypogonadism characterize Kallmann syndrome, resulting from defective migration of GnRH-producing neurons during fetal development.

Primary Ovarian Insufficiency

• Elevated FSH levels in amenorrhea indicate ovarian dysfunction, as seen in premature ovarian failure and Turner syndrome.

Medications

• GnRH agonists and antagonists are used to suppress LH and FSH secretion, with applications in treating cancers, endometriosis, and uterine leiomyomas.
• Assisted reproduction techniques, like IVF and ICSI, utilize FSH to stimulate follicle development in the ovaries, with GnRH agonists or antagonists used to prevent premature ovulation during treatment cycles.

Toxin Exposure and Endocrine Disrupting Chemicals (EDCs)

• Endocrine disrupting chemicals (EDCs) some text
  • EDCs are environmental toxins that interfere with hormone function in the body, including FSH regulation and ultimately impact fertility and reproductive health.  [16.]
  • Exposure to EDCs such as bisphenol A (BPA), phthalates, and parabens can disrupt the endocrine system's delicate balance, leading to alterations in FSH levels.
  • Many EDCs specifically act as xenoestrogens, synthetic chemicals that mimic estrogen in the body, disrupting hormonal balance and disrupting normal fertility mechanisms.  [9.]
• Heavy Metals [10.]some text
  • Heavy metal exposure, including lead, mercury, and cadmium, can disrupt hypothalamic-pituitary-gonadal function and potentially alter FSH levels, leading to hormonal imbalances and reproductive issues.
  • Heavy metals interfere with FSH regulation by disrupting signaling pathways and hormone production, potentially impairing fertility and reproductive health.

Effects of FSH Inhibition on Reproductive Health

Inhibited levels of FSH can significantly impact reproductive health, particularly in women. 

Without adequate FSH stimulation, ovarian follicles may fail to mature properly, leading to irregular or absent menstrual cycles and ovulation dysfunction. This can result in difficulties conceiving and infertility issues. 

Moreover, low FSH levels may disrupt the hormonal balance necessary for maintaining reproductive health, potentially contributing to conditions such as polycystic ovary syndrome (PCOS) or premature ovarian failure (POF). 

In men, inhibited FSH levels may affect spermatogenesis and testosterone production, potentially leading to reduced sperm quality and infertility.

Impact of Low FSH Levels on Fertility

Low FSH levels can have a profound impact on fertility, as FSH plays a crucial role in follicular development and ovulation in women, and spermatogenesis in men. In women, insufficient FSH stimulation can disrupt the ovarian cycle, leading to irregular or absent ovulation, which significantly reduces the chances of conception. 

Similarly, in men, low FSH levels may impair sperm production and quality, affecting fertility. 

Couples struggling with infertility often undergo FSH testing to assess ovarian reserve and sperm quality, providing valuable insights into potential fertility issues and guiding appropriate treatment strategies.

Supporting Healthy Levels of FSH 

Diet: maintain a balanced diet rich in essential nutrients, including antioxidants, vitamins, and minerals, which can support overall reproductive health.  Additionally, eating enough calories is essential to maintain hypothalamic production of GnRH. [13.]

Exercise: engage in regular exercise to promote blood circulation and hormone balance, as exercise may support healthy FSH levels in the follicular phase.  [11.]

Stress: manage stress through relaxation techniques such as meditation, yoga, or deep breathing exercises, as stress can negatively impact hormone levels and impair hypothalamic release of GnRH.  [18.]

Sleep: get adequate sleep to ensure proper hormone regulation and overall well-being. [4.]

Acupuncture: consider acupuncture or acupressure, which may help regulate hormone levels and improve reproductive function.  [3.]

Herbal Support: explore herbal supplements such as vitex (chasteberry), maca root, or red clover, which are believed to support hormonal balance and ovarian function.  [1., 8., 12.] 

Healthy Weight Management: maintain a healthy weight, as obesity or being underweight can disrupt hormone levels and fertility.  [7., 13.] 

Avoid Endocrine-Disrupting Chemicals: limit exposure to environmental toxins and endocrine-disrupting chemicals found in certain plastics, pesticides, and personal care products, as they can interfere with hormone regulation.  [17.]

Consult with a healthcare provider or naturopathic doctor for personalized recommendations and guidance on natural therapies to support normal FSH cycling.

Tests to Assess FSH Levels

Click here to discover various tests to assess FSH levels.