From the Guidelines
Negative feedback of female hormones plays a crucial role in maintaining hormonal balance and preventing overproduction, with estrogen and progesterone signaling back to the hypothalamus and pituitary to reduce GnRH, FSH, and LH production. The regulation of female hormones is essential for normal menstruation, fertility, and overall reproductive health in women. According to a study published in the Annals of Internal Medicine 1, the use of hormone therapy in postmenopausal women is associated with several potential benefits, but also substantial, well-documented harms. The negative feedback system involves the hypothalamus secreting gonadotropin-releasing hormone (GnRH), which stimulates the pituitary to release follicle-stimulating hormone (FSH) and luteinizing hormone (LH), prompting the ovaries to produce estrogen and progesterone. Some key points to consider about the negative feedback of female hormones include:
- Estrogen and progesterone levels rise sufficiently in the bloodstream to signal back to the hypothalamus and pituitary to reduce GnRH, FSH, and LH production
- The negative feedback system prevents hormonal overproduction and maintains appropriate levels throughout the menstrual cycle
- During the follicular phase, rising estrogen initially has a negative feedback effect, but switches to positive feedback briefly at high concentrations to trigger ovulation
- After ovulation, the corpus luteum produces progesterone, which exerts strong negative feedback on GnRH, FSH, and LH The study by the USPSTF 1 highlights the importance of considering the potential benefits and harms of hormone therapy in postmenopausal women, and the negative feedback system plays a critical role in maintaining hormonal balance and preventing overproduction.
From the Research
Negative Feedback of Female Hormones
The negative feedback of female hormones, particularly estrogen and progesterone, plays a crucial role in regulating the menstrual cycle and reproductive system.
- Estrogen, specifically estradiol (E2), has a negative feedback effect on the secretion of gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) during the follicular phase of the cycle 2.
- Progesterone also contributes to the negative feedback mechanism, regulating the secretion of LH and follicle-stimulating hormone (FSH) during the luteal phase 2.
- Inhibin B and inhibin A, non-steroidal substances produced by the ovaries, also participate in the negative feedback mechanism, controlling FSH secretion during the follicular and luteal phases, respectively 2.
Clinical Implications
The negative feedback of female hormones has significant clinical implications, particularly in the treatment of endometrial cancer and endometriosis.
- Hormonal therapies, such as progesterone and selective estrogen receptor modulators, are used to treat endometrial cancer, especially in patients with low-grade disease and hormone receptor positivity 3, 4.
- Progestogens, including levonorgestrel intrauterine devices, are effective in preventing and treating endometrial hyperplasia and atypical hyperplasia, and may also be used to treat endometriosis 4, 5.
- The use of hormonal contraceptives, such as extended-cycle pills with low-dose estrogen and levonorgestrel, can also have a negative feedback effect on the ovaries, reducing the risk of endometrial cancer and endometriosis 6.
Mechanism of Action
The negative feedback mechanism of female hormones involves the regulation of GnRH and gonadotropin secretion by steroidal and non-steroidal substances produced by the ovaries.
- Estradiol (E2) plays a key role in the negative feedback mechanism during the follicular phase, while progesterone and inhibin A contribute to the regulation of LH and FSH secretion during the luteal phase 2.
- Disturbances in the feedback mechanisms can occur in various abnormal conditions, such as polycystic ovary syndrome (PCOS), or after treatment with pharmaceutical compounds that interfere with the production or action of endogenous hormones 2.