What is the negative feedback cycle in female reproduction, specifically regarding the regulation of the menstrual cycle and hormone levels, including the role of estrogen (oestrogen) and progesterone?

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Last updated: May 14, 2025View editorial policy

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From the Research

The negative feedback cycle in female reproduction is a complex process involving the hypothalamus, pituitary gland, and ovaries, which work together to regulate hormone levels throughout the menstrual cycle, with the most recent evidence suggesting that clomiphene citrate is the first-line treatment for ovulation induction in anovulatory patients with polycystic ovary syndrome (PCOS) 1.

Key Components of the Negative Feedback Cycle

  • The hypothalamus releases gonadotropin-releasing hormone (GnRH), which stimulates the pituitary to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH) 2.
  • These hormones promote follicle development and estrogen production in the ovaries, with estrogen levels initially exerting negative feedback on the hypothalamus and pituitary, reducing FSH secretion to prevent multiple follicles from developing 3.
  • However, when estrogen reaches a critical threshold, it briefly switches to positive feedback, triggering the LH surge that causes ovulation, with the corpus luteum forming and producing progesterone, which exerts negative feedback on the hypothalamus and pituitary, suppressing GnRH, FSH, and LH 4.

Treatment of PCOS

  • Clomiphene citrate is the first-line treatment for ovulation induction in anovulatory patients with PCOS, with a study showing that the ovulation rate was 59% in the clomiphene citrate group, compared to 23.7% in the metformin group, and 68.4% in the combination treatment group 1.
  • Another study found that letrozole-metformin therapy was more effective than clomiphene citrate-metformin therapy in moderately obese patients with PCOS who are resistant to clomiphene citrate alone, with a higher pregnancy rate after the third IUI cycle in the letrozole group (20.6%) compared to the clomiphene citrate group (9.6%) 3.

Conclusion Not Applicable

Instead, the following key points should be considered:

  • The negative feedback cycle in female reproduction is a complex process that involves the hypothalamus, pituitary gland, and ovaries.
  • Clomiphene citrate is the first-line treatment for ovulation induction in anovulatory patients with PCOS.
  • Letrozole-metformin therapy may be more effective than clomiphene citrate-metformin therapy in moderately obese patients with PCOS who are resistant to clomiphene citrate alone.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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