A while ago, an article titled "Before I Was 23, I Had No Libido" went viral online. It brought to the public's attention an extremely rare disease (with an incidence rate of approximately 1 in 8000 men and 1 in 40000 women): Kallmann syndrome (KS), which is essentially hypogonadotropic hypogonadism (IHH).
Yes, you read that right. Today we're going to have a serious talk about sex.
At the recent 18th National Congress of Endocrinology of the Chinese Medical Association (CSE2019), topics related to the gonads also attracted much attention from the attending clinicians:
"Medical Community" was fortunate to have Professor Wu Xueyan from Peking Union Medical College Hospital at the event, who shared his insights on the treatment of gonadal diseases:
01
Sexual issues are not necessarily related to the reproductive organs.
Professor Wu Xueyan:
"Gonadal issues are often related to the most basic fertility issues, which I think is why many doctors are here today to attend the gonadal-themed lecture."
Gonadal disorders are among the most difficult to document and treat consistently. Patients are often reluctant to seek medical help due to stigma, making it challenging for doctors and researchers to collect sufficient case studies. When discussing the gonads, one must mention one of the three major branches of the human endocrine system: the hypothalamic-pituitary-gonadal axis.
“In the past, our endocrinology department mainly treated gonadal diseases with hormone injections, which was a targeted approach. Women’s ovulation problems and men’s secondary sexual characteristics development problems were all solved with corresponding hormones,” Professor Wu Xueyan pointed out. “But we later discovered that treating the symptoms with hormones only addresses the symptoms, not the root cause. Many patients’ gonadal secretion function was clearly normal, so the problem must have been with a higher-level secretory center.”
In recent years, Professor Wu Xueyan and his team have been focusing on the study of the central endocrine organs upstream of the gonads—the hypothalamus and pituitary gland. From December 2017 to December 2018, a clinical study was jointly completed by Professor Wu Xueyan's team at Peking Union Medical College Hospital, Professor Guan Qingbo's team at Shandong Provincial Hospital, and Professor Tian Long's team at Beijing Chaoyang Hospital—to evaluate the pituitary-gonadal axis function of subjects using short-term GnRH pulse therapy.
This study recruited 30 patients diagnosed with idiopathic hypogonadotropic hypogonadism (IHH). After discontinuing symptomatic hormone therapy such as estrogen, androgens, and progesters, patients were treated with gonadotropin-releasing hormone (GnRH, secreted by the hypothalamus and acting on the pituitary gland) supplementation via a hormone pump to stimulate the pituitary gland in a manner mimicking physiological secretion. Results showed that all subjects experienced a significant increase in follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels compared to pre-treatment levels.
"This shows that a large proportion of patients have normal pituitary and gonadal functions, but because the signal transmission between the hypothalamus and pituitary gland is blocked, it ultimately manifests as gonadal secretion problems," Professor Wu Xueyan said. "This also suggests that many gonadal secretion problems may eventually be resolved by addressing the central nervous system."
02
Simulates physiological drug administration,
Pulsating hormone pumps: a new option for gonadal therapy!
Professor Wu Xueyan explained:
"Under physiological conditions, the onset of puberty in our bodies is marked by the pulsatile release of GnRH during hypothalamic sleep. If the secretion of GnRH pulsatiles in the hypothalamus is abnormal during puberty, delayed puberty, low sex hormone levels, failure to develop secondary sexual characteristics, infertility, etc., will occur. This is also the cause of idiopathic hypogonadotropic hypogonadism (IHH)."
As growth and development progress, the hypothalamus gradually develops regular GnRH pulsatile peaks in hormone secretion, with a frequency of approximately 60–90 minutes per pulse. GnRH pulsatile secretion stimulates pituitary LH and FSH, which in turn promotes the secretion of sex hormones and gamete production in the gonads, forming a hypothalamic-pituitary-gonadal axis feedback and negative feedback system. In the past five years, this physiological pulsatile hormone administration method has been gradually applied clinically, and Professor Wu Xueyan and his team of two other professors have conducted research based on this clinical data.
Professor Wu Xueyan believes that "although modern pituitary hormone pump therapy has only been used for about 5 years, this treatment method is closer to physiology and its efficacy is superior to other traditional therapies." The results of this study have added new clinical evidence for this therapy.
03
Pituitary hormone pump therapy can also be extended to the field of diagnosis.
Professor Wu Xueyan believes that the application of pituitary hormone pumps is not only limited to the treatment of gonadal diseases, but can also help clinicians accurately diagnose gonadal diseases. Many endocrinologists have likely encountered this problem: when a patient with gonadal dysfunction comes to you, how do you determine whether it's a gonadal problem, a pituitary problem, or a hypothalamic problem? A pituitary hormone pump might be able to help.
Professor Wu Xueyan explained the diagnostic function of the pituitary hormone pump as follows:
"A short-term treatment with a pituitary hormone pump for about a week can more accurately determine the function of the pituitary-gonadal axis. If the patient's hormone levels improve after treatment, it is very likely that there is a problem with hormone transmission between the hypothalamus and the pituitary gland. However, if there is no improvement, it is possible that there is an abnormality in the function of the gonads and pituitary gland themselves."
In addition, he mentioned that the new generation of hormone pumps are now equipped with Bluetooth functionality to download data to smartphones. With the help of an app, long-term management of patients can be achieved, which is of great significance for the treatment and research of these rare diseases.
In addition to Professor Wu Xueyan, Professor Guan Qingbo of Shandong Provincial Hospital, another participant in the study, also shared his views at the invitation of "Medical World":
The biggest advantage of pituitary hormone pumps is that they can mimic physiological pulsatile GnRH secretion, which is more in line with the patient's physiological needs than direct injection of hormones.
On the other hand, compared to hormone injections 2-3 times a week, portable pituitary hormone pumps are more convenient and can reduce invasive procedures, making them a treatment method worthy of widespread adoption in clinical practice.
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