For over 15 years, Dr Anthony Shum, a pulmonologist at the University of California, San Francisco has been studying a rare genetic disorder called the COPA Syndrome. It stands for coatomer subunit alpha and is a rare, inherited disorder that affects the lungs, joint, and kidney. The National Organization for Rare Disorder also notes that it is a genetic autoimmune disorder that is caused by mutations in the COPA gene. This disease affects families unpredictably—some individuals with the mutation develop severe lung damage early in life, while others remain completely healthy. Now, Shum’s team has discovered a protective genetic variant that may offer new hope for treatment.

A Breakthrough

Researchers found that some relatives of COPA Syndrome patients stayed healthy despite carrying the same COPA gene mutation that causes the disease. The key difference? These unaffected individuals had a protective version of another gene called HAQ-STING.

When scientists introduced HAQ-STING into diseased lung cells from COPA patients, the cells returned to a balanced state, suggesting that this gene could be used as a therapy.

“We really think HAQ-STING could be a gene therapy tool and a step toward a cure,” said Shum, whose findings were published in the Journal of Experimental Medicine.

Families Who Solved The Mystery

Shum’s journey into COPA Syndrome research began in 2011 when he treated a young woman, Letasha, who had severe lung bleeding. Her mother, Betty Towe, mentioned that Letasha’s sister, Kristina, had suffered from similar symptoms. Over the years, Betty had taken both daughters on a four-hour trip to UCSF for treatment. After tracing their family history, Shum discovered that their distant relatives in Texas and Oakland also had lung problems and arthritis. In 2015, Shum, along with scientists from Baylor College of Medicine and Texas Children’s Hospital identified the COPA gene mutation. They realized that it was the common factor behind the illness. However, only some of the 30 individuals with the mutation actually developed symptoms, leaving a major question unanswered.

The Domino Effect

It was established that it occurs when a mutated COPA gene causes another gene STING to go overdrive. The STING that helps fight infections in COPA patients, remain permanently active, which leads to chronic inflammation that damages the lungs, kidneys, and joints. In 2020, while studying STING’s role in the disease, researchers discovered a key variation: HAQ-STING. This version of STING, present in about one-third of the population, appeared to neutralize the harmful effects of the COPA mutation.

To confirm their theory, the scientists needed both affected and unaffected family members to participate in the testing. Letasha, Kristina and Betty immediately volunteered. The researchers then analyzed DNA samples from 26 COPA patients and their healthy relatives. They also conducted CT scans and blood tests to ensure that unaffected members did not have any hidden symptoms. When the findings were all clear, it was revealed that all the healthy individuals had HAQ-STING, while none of the COPA patients did. This was the first known case of a common gene variant completely protecting against a severe genetic disease.

Encouraged by this discovery, researchers tested HAQ-STING’s effects in a lab setting. They introduced it into diseased lung cells from COPA patients, and the cells returned to normal function.

Way Ahead

Shum believes HAQ-STING could lead to game-changing treatments, including:

• Prenatal gene therapy for babies diagnosed with COPA Syndrome before birth
• Aerosol delivery of HAQ-STING for adults, directly targeting the lungs

Before publishing their findings, Shum called Betty with the news—her own HAQ-STING gene had protected her from the disease. He also informed Letasha and Kristina, who were overwhelmed with relief and joy.

“We always believed Dr. Shum would get to the bottom of it,” said Letasha. “This discovery is going to change lives.”

Menopause typically occurs between the ages of 45 and 55. However, the hormonal changes leading up to it can begin earlier, with some women reporting symptoms in their 30s.

A 2025 study published in NPJ Women's Health examined 4,400 American women aged 30 and older. It found that roughly 55% of women aged 30-35 reported moderate or severe symptoms on the Menopause Rating Scale. The proportion rose to just over 64% among women aged 36-40. Despite these symptoms, most women did not seek treatment until they were 56 or older.

Speaking to HealthandMe, Dr. Kajal Parikh is an Obstetrician and a Gynecologist based in Mumbai, explained how hormonal changes can begin in the mid-to-late 30s, the signs women should watch for, and why monitoring symptoms and maintaining healthy habits matter during this transition.

Perimenopause Can Begin In Your Mid-To-Late 30s

From the first menstrual period to menopause, the body undergoes significant hormonal changes. Estrogen and progesterone are among the hormones involved in this process.

“These hormones don't exit overnight. The exit starts much earlier. Starting mid-30s to late 30s, the hormone levels start depleting. Now, when that level starts depleting, you're going to see signals.”

According to Dr Parikh, changes in menstrual cycles can be among the first signs. Periods may become heavier or lighter, while cycles may become shorter or longer.

Being mindful of these changes can help women identify patterns and discuss persistent or concerning symptoms with a healthcare professional. However, these symptoms alone do not confirm that a woman is in perimenopause.

Also read: Menopause Abruptly Shifts Bones, Liver And Blood Fats, Study Finds

Brain Fog, Sleep Problems And Other Signs To Watch For

Perimenopause symptoms can extend beyond menstrual changes. Women may notice dry skin, pigmentation, hair thinning, increased hair fall, low energy, brain fog and disturbed sleep.

Some women who previously slept well may begin waking up at 3 or 4 a.m. and find it difficult to return to sleep, Dr Parikh told HealthandMe.

“That's your body asking for some help, or rather the body signaling that we are going through some crisis, see how we can fix it.”

Other possible symptoms include breast tenderness, worsening premenstrual symptoms, headaches, migraines, and bone and joint pain. Vaginal dryness, changes in urinary habits and reduced libido may also occur.

Symptoms vary considerably between individuals, and many of these changes can have causes other than perimenopause, the expert said,

When Should Women Seek Medical Advice?

Read More: ‘I Was Vocal About Cancer But Silent About Menopause Out Of Shame’, Says Actress Lisa Ray

Dr Parikh recommended annual gynecological visits to monitor changes over time. She also advised women to track their symptoms and seek medical advice if they worsen or do not improve with treatment.

Although menstrual changes may become noticeable in the late 30s and early 40s, the timing of the menopausal transition varies. Some women experience menopause earlier than expected, while others continue menstruating into their 50s.

For women without symptoms, Dr Parikh identified 40 as an appropriate age to begin regular monitoring and annual screening.

“40 is that golden age when you start monitoring, when you start getting your annual screenings done.”

The need for specific tests depends on a woman's age, symptoms and medical history. Women experiencing menstrual changes or possible menopausal symptoms at a younger age should consult a healthcare professional rather than waiting until 40.

What Tests And Lifestyle Changes Can Help?

Dr Parikh said doctors may assess iron levels, thyroid function, blood sugar and lipid levels while reviewing a woman's diet, nutrition and exercise habits. These assessments can help identify other conditions that may contribute to symptoms.

She also emphasised the importance of sleep, nutrition and exercise during the menopausal transition.

“The only thing that will save you from this transition are your three strong pillars, which is your sleep, your nutrition, and your exercise regimen.”

Treatment depends on the symptoms and individual health needs. After assessing symptoms and ruling out other possible causes, doctors can discuss appropriate options, including hormone therapy when indicated.

READ: Can Menopause Be Delayed? What Science Says About Slowing Ovarian Aging

Can Genetics Influence Menopause Timing?

Dr Parikh said genetics can play a role in determining when menopause occurs. A family history of early menopause, including in a woman's mother or grandmother, may be relevant when discussing her own reproductive health.

She also raised concerns about potential environmental exposures, including endocrine-disrupting chemicals found in some products and packaging. However, their individual contribution to the timing of menopause is difficult to establish, and these exposures should not be presented as proven causes of early menopause.

Maintaining a balanced diet, exercising regularly and prioritising sleep can support overall health during the menopausal transition.

For a patient with advanced heart failure, there comes a point when medicines, devices and repeated hospitalisations can no longer control the disease. For some, a heart transplant may offer the only realistic path to long-term survival. Yet in India, the challenge often begins much earlier than the waiting list: many patients who could potentially benefit from transplantation never reach an advanced heart-failure or transplant centre for evaluation.

The scale of the problem is enormous. A recent study found that 83,000 heart transplantations were required annually in India in 2021, although only a very small proportion of that need was met. In comparison, according to the National Organ and Tissue Transplant Organisation (NOTTO), 221 heart transplants were performed in 2023.

Why Patients With Advanced Heart Failure Miss Out

The first issue is delayed referral. Patients with advanced heart failure may continue to be treated repeatedly for breathlessness, fluid retention or hospital admissions without being assessed early for advanced therapies.

A transplant evaluation is not a last-minute decision. It requires time to assess the patient's medical condition, other organs, infection risk, nutrition, psychosocial circumstances and ability to undergo lifelong follow-up.

The second challenge is the limited availability of donor hearts. Heart transplantation depends almost entirely on deceased organ donation. India has made substantial progress in transplantation overall, but the national deceased organ donation rate remains less than one donor per million population.

How Geography And Cost Affect Access To Transplants

Geography and affordability also matter. Advanced heart-failure programmes and transplant centres are concentrated in selected regions, meaning that patients from smaller cities and rural areas may face substantial travel, financial and logistical barriers.

The cost of evaluation, repeated hospitalisations, mechanical circulatory support and post-transplant medicines can further influence whether a patient can realistically pursue transplantation.

Also read: “You’ve Got A Pig’s Heart!” Genetically Modified Pigs with Human-like Organs Transforming Organ Donation; Details Inside

When Should Patients Be Referred To A Transplant Centre?

We therefore need to change the way advanced heart failure is recognised. A patient with recurrent hospitalisations, persistent symptoms despite optimal therapy, progressive kidney or liver dysfunction, low blood pressure limiting medications, or dependence on intravenous therapies should trigger consideration of referral to an advanced heart-failure centre.

Early referral gives specialists more time to evaluate the patient, assess treatment options and determine whether transplantation or another advanced therapy is appropriate.

Heart Transplant Is Not The Only Advanced Treatment

Importantly, transplantation is not the only advanced therapy. Left ventricular assist devices (LVADs) can serve as a bridge to transplantation or, in selected patients, as long-term therapy.

These devices can help support the heart's pumping function in patients with advanced heart failure who meet the criteria for their use. The appropriate option depends on the patient's condition, overall health and treatment goals.

India has demonstrated that transplantation can grow rapidly when infrastructure, coordination and public awareness improve. The next step is to ensure that patients are identified early enough to be evaluated, and that a shortage of donor organs does not remain the only reason they never get the opportunity to reach the transplant list.

By Dr. Pravin Kulkarni, MBBS, MS (General Surgery), MCh (Cardiovascular and Thoracic Surgery), Fellowship in CTS, Director, Advanced Cardiac Surgery and Heart and Lung Transplant Program

According to the latest National Family Health Survey (NFHS-6), 30.7% of women aged 15-49 years in India are reported as overweight or obese, highlighting the growing importance of lifestyle factors in women’s reproductive and overall health. Along with nutrition and physical activity, sleep is another important factor for overall menstrual health and the ovulation cycle.

Ovulation is controlled by a complex interaction between the brain, pituitary gland and ovaries. This reproductive hormone system is closely connected to the body's circadian rhythm, which regulates the sleep-wake cycle and influences the timing of several hormonal processes. When sleep becomes consistently irregular or insufficient, these signals may become disrupted, potentially affecting the hormonal coordination required for normal ovulation.

How Sleep Disturbances May Affect Reproductive Hormones

Also read: Andrew Huberman’s Sleep Trick: Can Eye Movements Help You Fall Back Asleep?

One of the ways this may occur is through interference with the functioning of the hypothalamic-pituitary-adrenal (HPA) axis. The reproductive system relies on communication between the hypothalamus and pituitary gland to regulate the hormones involved in follicle development and egg release.

Melatonin is another hormone linked to sleep and circadian rhythm. It also has antioxidant properties in the ovaries. This is why the relationship between sleep and fertility may involve more than simply the number of hours a woman sleeps.

A 2025 study published in Chronobiology International found that a later chronotype, or a tendency to sleep and wake later, was associated with a higher risk of sporadic anovulation among women with regular menstrual cycles.

Each one-hour increase in later chronotype was associated with a 5% higher relative risk of anovulation (RR 1.05; 95% CI 1.00–1.11), while women in the third chronotype tertile had a 33% higher relative risk compared with those in the second tertile (RR 1.33; 95% CI 1.05–1.68).

Interestingly, sleep duration itself was not associated with anovulation, suggesting that sleep timing and circadian patterns may also matter.

Poor Sleep Quality May Also Matter During IVF

Sleep may also be relevant during fertility treatment. A 2025 prospective cohort study of 174 women undergoing IVF/ICSI reported that women with poor sleep quality had 22.89% fewer retrieved oocytes and 22.01% fewer matured oocytes after adjustment for relevant factors.

The study also reported associations between certain sleep patterns and other IVF outcomes. However, these findings are observational and do not establish that poor sleep directly causes poorer fertility outcomes.