Even men and women who appear hormonally “normal” can have unrecognized disruptions in the timing and regulation of their reproductive hormones, impairing their fertility, according to research presented at the 28th European Endocrinology Congress in Prague. A newly developed wearable skin sensor patch, combined with artificial intelligence (AI), can now measure not only the amount of reproductive hormones, but also how they change over time, potentially helping patients and doctors detect infertility early and improve fertility.
Unexplained infertility affects approximately 15-30% of couples and is diagnosed after standard tests find no obvious cause. Standard testing for men with infertility or hypogonadism (clinically low testosterone) includes a single morning serum testosterone measurement, while infertility testing for women includes evaluation of menstrual cycles and reproductive hormones such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, and progesterone. However, hormones are highly dynamic, following circadian rhythms, rising and falling in a regulated pattern throughout the day.
In one study, Dr. Tinatin Kuchukhidze from the University of Oxford and the University of New Anglia tested 102 men in Georgia and the United Kingdom, aged 22 to 38, with normal morning total testosterone levels (12 to 35 nmol/l), regardless of whether they had infertility or hypogonadal symptoms. Using the AI-enabled wearable skin sensor patch they developed, she and her team analyzed data on testosterone levels every 15 minutes over four days and found that men with symptoms had significantly disrupted testosterone rhythms, even though their testosterone levels were normal on standard clinical tests. Furthermore, these unmasked rhythm abnormalities were associated with decreased sperm concentration and symptoms of androgen deficiency.
“For the first time, it is now possible to track androgen patterns in real-time over several days using a novel, non-invasive, AI-powered continuous testosterone monitoring patch that is compatible with Android and iPhone mobile devices,” said Dr. Kutchukhidze. “Previous studies have suggested that normal morning testosterone levels are sufficient to rule out clinically significant androgen deficiency. However, our findings challenge that assumption by showing that even men with normal serum testosterone can exhibit marked disturbances in hormonal rhythms associated with reproductive dysfunction,” said Dr. Kuchukhidze.
In another study, Dr. Kutchikhidze and colleagues developed an AI-driven measure, the Endocrine Rhythm Integrity (ERI), and analyzed data on key reproductive hormones, basal body temperature, heart rate, and sleep patterns during the luteal phase of 312 women ages 18 to 22 who had self-reported regular menstrual cycles, were fertile, or had unexplained infertility. She found that women with unexplained infertility had lower ERI scores, which predict infertility, even if their hormone levels were normal. Lower ERI scores were also associated with higher incidence of implantation failure.
“Our study revealed that even though women have seemingly healthy menstrual cycles and normal hormone levels, they may be experiencing hidden endocrine insufficiency that affects their ability to conceive,” said Dr. Kuchukhidze. “Rather than analyzing hormone levels as isolated values, ERI assesses whether reproductive hormones are changing in the right pattern, at the right time, and in the right relationship to each other throughout the menstrual cycle.”
“Our AI-driven rhythm analysis is significantly better at identifying subclinical reproductive dysfunction than traditional tests, suggesting that endocrine disorders in women and men may not simply be disorders of hormone levels, but rather disorders of hormonal timing, synchrony, and biological rhythms,” said Dr. Kuchukhidze.
Dr. Kutchukhidze will next assess whether this new tool can reliably predict birth outcomes across a range of reproductive conditions in larger and more diverse populations.
“We aim to move infertility treatment toward predictive, rhythm-based reproductive medicine, where clinicians can identify dysfunction early, personalize interventions, and improve outcomes before infertility becomes clinically apparent,” said Dr. Kuchukhidze. “If successful, this research could lead to the first clinically practical tool to measure endocrine rhythm health and redefine how fertility is assessed around the world.” “Importantly, this technology also has the potential to be broadly applicable to transgender medicine, where hormone therapy currently relies on intermittent blood tests that may not reflect real-time hormone dynamics. Our long-term goal is to establish wearable hormone time diagnostics as a new standard not only in reproductive medicine and personalized endocrinology, but also in transgender medicine, enabling more accurate, adaptive, and patient-centered management across diverse clinical settings.” ”
sauce:
European Endocrine Society
