on April 23, 2025
As discussed in the previous article, the female physiological cycle runs on a cycle that is coordinated and controlled by the hypothalamic-pituitary-ovarian (HPO) axis. This axis maintains menstruation, fertility, and changes that come with aging by sending regular hormonal signals between different parts of the body. But when this system doesn’t work properly, it can lead to problems like amenorrhea during adolescence or hot flashes during menopause.
The Disease Spectrum of HPO Axis Dysfunction
Hypothalamic Amenorrhea: When the Body Puts Reproduction on Hold
When there is chronic stress or extreme restriction in calorie intake, it can stop the hypothalamic pulse generator, while reducing blood oxygen levels by 35% in arcuate nucleus neurons. It is mostly dancers and athletes who often experience amenorrhea, which means their menstruation stops as their ovaries enter a kind of sleep mode. Even after gaining weight back, it can take months for the brain to re-establish GnRH pulsatility, showing the memories of the nervous system of remembering the stress the body went through.
Polycystic Ovary Syndrome (PCOS): A Hormonal Feedback Trap
High levels of androgens (male hormones) can block follicular development similar to a lock that stops the process from moving forward. The brain starts sending faster signals, doubling the LH hormone levels and tells the ovaries to overproduce androgens. This sets off a cycle where progesterone gets turned into even more of these hormones.
Moreover, insulin resistance makes the condition worse—free fatty acids release substances that reduce how well the ovaries respond to FSH through a chain reaction in the body, increasing testosterone by 40%. This ends up with ongoing acne and thinning of hair.
Perimenopausal Storm: The Pain of Neuronal Regression
As the ovaries lose, their egg reserves and estradiol levels drop sharply from 300 pg/mL to very low levels. This becomes a problem in certain brain cells in the hypothalamic thermoregulatory center, which help control body temperature. KNDy neurons start to malfunction, with their numbers dropping by about 60%. This triggers hot flashes in roughly 75% of women. Research shows that during each hot flash, the temperature in the brain rises quickly by 0.5°C in just 30 seconds, almost like a sudden heatwave hitting the brain.
Endometriosis: The Hidden Inflammatory Disruptor
Ectopic endometrial tissue is not just an unwanted presence in the pelvic area but also actively interferes with the HPO axis. Inflammatory substances released by these growth stop hormone signals, reducing the LH surge by 28% and shortening the luteal phase to less than 10 days. Even worse, local estradiol production can reach levels up to 10 times higher than in the rest of the bloodstream, setting off a harmful cycle that keeps fueling the problem.
Scientific Strategies for Rebalancing
Early warning signs of HPO axis imbalance often show up as menstrual cycles that vary by more than seven days. Monitoring biomarkers such as AMH and the LH/FSH ratio can help predict ovarian function changes in advance. Managing metabolism should be focused and maintaining a healthy body fat percentage between 22% and 28% can help, as fat tissue releases adiponectin, which improves ovarian response to FSH.
It is important to manage stress too. Eating tryptophan-rich foods (like pumpkin seeds and dark chocolate) supports increasing serotonin levels, while lifestyle changes—such as following a low-fat, low-sugar Mediterranean diet—have been effective in balancing hormones. For women in perimenopause, new non-hormonal drugs targeting NK3R are under development and have shown promising results in reducing hot flash frequency in clinical trials.
Conclusion
Every fluctuation of the HPO axis is the body speaking in its own language. From hormonal tides to metabolic shifts, these signals are worthy of having close attention. There is no need to be worried about temporary imbalances as science offers us with the tools to decode them. By tracking cycle changes, optimizing nutrition, and learning to manage stress, women can regain control of their health within a state.
Remember: caring for the rhythm of life is the most tender form of self-care