Advancements in Femtech

US20200268440A1 from Acessa Health titled Automated ablation control systems describes an automated ablation control system comprising a surgical workstation having robotic arm assemblies for ablation of a uterine fibroid. This system also includes ultrasound instrument coupled to robotic arm assembly. The ablation instrument has multiple deployable stylets reconfigurable from low-profile to a deployed configuration. The ablation instrument and imaging instrument are coupled to different robotic arm assemblies^[22].

Solutions available during Crone stage:

Health & Her Menopause Tracker: Health & Her helps in menopause management. It includes several alternative techniques to treat various symptoms of menopause, such as cognitive behavioral therapy (CBT) for hot flashes, depression and night sweats. Also provided are guided imagery meditation for insomnia and deep breathing for stress and anxiety.

In addition, this app offers standard symptom-tracking tools as well as a menstrual cycle monitor for perimenopausal women. Various “clinically proven” supplements and menopause products are available to purchase through Health & Her ^[34].

UK-based KaNDy Therapeutics is working on a dual NT-814, neurokinin-1,3 receptor antagonist, developed as a non-hormonal alternative to hormone replacement therapy for treating postmenopausal symptoms (PMS). Founded in 2017 and acquired by Bayer, KaNDy Therapeutics is a spin-off from NeRRe Therapeutics Ltd.^[35]. It has recently completed the Phase IIb trial of NT-814, and is now regarded as BAY3427080 (Elinzanetant), which is in phase 3 ^[36].

WO2019175253A1– titled Novel pharmaceutical formulation comprising dual nk-1/nk-3 receptor antagonists filed by KaNDy Therapeutics describes a pharmaceutical formulation containing 2-[3,5-Bis(trifluoromethyl)phenyl]-N-{4-(4-fluoro-2-methylphenyl)-6-[(7S,9aS)-7- (hydroxymethyl) hexahydropyrazino [2,1-c][1,4]oxazin-8(1H)-yl]-3-pyridinyl}-N,2-dimethylpropanamide, for use in the treatment or prevention of a sex hormone dependent disease, or a condition associated with the perimenopause, the menopause, or the post menopause ^[37]. Kandy Therapeutics was acquired by Bayer in August 2020.

Scientists are also studying very different approaches for treating menopausal conditions in women. One such interesting approach is described in US11260087B2, titled ‘Composition for preventing or treating menopause’. The patent filed by Korea Food Research Institute, describes a novel Lactobacillus acidophilus YTI strain and a composition containing the same for treating Menopause. When compared to other strains of Lactobacillus in menopausal rat models (with ovariectomy), Lactobacillus acidophilus strain showed increase in femoral bone mineral density (BMD), which was confirmed by using a bone densitometer. It also showed decrease in pain sensitivity when compared with Lactobacillus (L. reuteri) which was confirmed by von Frey filament test ^[38].

B) Cardiovascular Health, Mental Health, Bone Health and Cancers:

In addition to the above, Femtech companies have also been focusing on cardiovascular, mental, bone health and cancers that affect women.

a) Cardiovascular Health

Women manifest cardiovascular disease symptoms differently from men. In premenopausal women, estradiol (E2) provides overall cardio-protection from vascular dysfunction and cardiovascular disease. Due to the influence of estradiol, women’s blood pressure and platelets react differently under stress. Increase in the number of platelets and reduction in microvascular blood flow can cause ischemia in critical organs such as the heart ^[39].

According to Prof. Hugo Katus, the Chair of European Society of Cardiology Advocacy Committee, cardiovascular diseases kill more women than men, and particularly, in women aged 65 years or less as compared to breast cancer, more than twice the number of women die of cardiovascular diseases. Unfortunately, cardiovascular mortality in women is – in contrast to cancer – not on a decline but has stagnated or increased and many women live with chronic, non-curable cardiovascular diseases^[40].

According to Dr. Annemarijn de Boer of the University Medical Centre Utrecht, the Netherlands, heart attack symptoms are often labelled as ‘typical’ in men and ‘atypical’ in women. However, while symptoms can differ between the sexes, there are also many similarities. A compilation of 27 studies from the past two decades detailing symptoms in patients with confirmed acute coronary syndrome showed that compared to men, women were more than twice as likely to have pain between the shoulder blades, 64% more likely to have nausea or vomiting, and 34% more likely to experience shortness of breath. Although chest pain and sweating were the most frequent symptoms in both women and men, they occurred less often in women^[41].

b) Mental Health Changes:

It is known that perimenopausal women experience more symptoms of depression than premenopausal women^[42]. It was observed in a study, that amplitude of low-frequency fluctuation (ALFF) and gray matter volume (GMV) values of certain brain regions related to cognitive function were different in perimenopausal women^[43]. Women not only have a higher prevalence of Alzheimer’s disease than men of the same age, but also show significant greater decline and deterioration^[44].

WO2018053595A1 from Newcastle University, titled Methods for improving cerebrovascular function and cognition in peri- and post-menopausal women, describes a method for improving cerebrovascular function and cognitive performance by administering an effective amount of resveratrol. The inventor’s hypothesis is that resveratrol elicits its benefits on cognition and mood through its ability to modulate cerebral perfusion during times of demand. The beneficial effects observed may be due to actions of resveratrol, either directly or indirectly, on estrogen receptors in the brain. The estrogen receptors may be α or β- receptors ^[45].

The Tulane Brain Institute, founded in 2016, focuses on understanding why estrogen therapy helps protect some women from age-related brain problems. The $14 million NIH grant to study why heart disease, diabetes may blunt brain benefits of estrogen therapy, will determine if and how estrogens interact with cardiovascular and metabolic health to impact the brain and cognitive aging ^[46].

c) Bone Health:

It is known that after menopause, women’s bodies produce low levels of estradiol. A study demonstrates that estrogen plus progestin increases Bone Mineral Density (BMD) and reduces the risk of fracture in healthy postmenopausal women ^[47]. In another study, it was observed that ultra-low doses of estradiol may potentially prevent bone loss in old women ^[48]. In another study, a five-year sequential therapy with estrogen and progesterone can increase or maintain the BMD of women in their menopausal transition and early menopause ^[49].

d) Cancers:

MammoRisk®, the breast cancer risk prediction solution from Predilife, offers women in Europe a clear report for personalized screening. “Polygenic Risk Score” is performed through genotyping of saliva samples. A mammogram may be recommended based on the genetic screening. DenSeeMammo and MammoRisk software developed by Predilife show good correlation between the breast density assessed by AI software (DenSeeMammo) and an assessment by a radiologist. Predilife developed the AI-based software in collaboration with the Radiology Department of the AP-HP Sorbonne University Hospital in Tenon, Paris ^[50].

Olema Oncology, a clinical-stage biopharmaceutical company, is focusing on developing targeted therapies for women’s cancers ^[51]. OP-1250 is an oral compound that antagonizes the estrogen receptor (ER) and blocks the ER-mediated cancer cell growth and proliferation signal.

In July 2022, the U.S. Food and Drug Administration (FDA) granted Fast Track designation to OP-1250, the company’s novel, oral estrogen receptor (ER) antagonist (CERAN) and selective ER degrader (SERD), for the treatment of ER-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer that has progressed following one or more lines of endocrine therapy with at least one line given in combination with a cyclin-dependent kinase (CDK) 4/6 inhibitor. OP-1250 is currently being evaluated as a single agent in an ongoing Phase 1/2 clinical trial and in Phase 1b in combination with Palbociclib, in patients with recurrent, locally advanced or metastatic ER+/HER2- breast cancer.

Alternative therapies:

Alternative therapies available to women include herbal extracts, particularly in Asian countries

In addition to estrogenic activity, herbal extracts provide many other benefits to women.

Some of the herbs that possess estrogenic activity as well as other additional benefits have been presented with animal study evidences.

• Praval bhasma is effective in the prevention of calcium and estrogen deficient bone loss.
  Animals with ovariectomy and concurrent calcium deficiency (CD-OVX) showed increase in urinary excretion of calcium (Ca) and phosphorus (P), decrease in femoral weight and density, which were significantly reversed in Praval bhasma-treated animals ^[52].

• Dalbergia sissoo leaves are used for the treatment of neurological disorders. They exhibit anti-inflammatory, anti-oxidant effects and also estrogenic properties. Ethanolic extract of Dalbergia sissoo leaves (3- Nitropropionic acid) significantly attenuated behavioral alterations, oxidative damage, mitochondrial dysfunction, and striatal/hippocampus damage in 3-Nitropropionic acid treated rats^[53].
• Asparagus racemosus, Cissus quadrangularis, Punica granatum and Pueraria tuberosa extracts show potential estrogenic activity and help in the treatment of postmenopausal osteoporosis. The animals treated with a mixture of extracts of four drugs, namely Asparagus racemosus, Cissus quadrangularis, Punica granatum and Pueraria tuberosa extracts showed significant increase in uterine weight, femur BMD, femur hardness, levels of calcium and phosphorus in serum and significant decrease in urine as compared to the control group ^[54].
• Ginger and cardamom show estrogenic effect, and also help in improving learning and memory⁵⁵.

Many patents have been filed from Asian countries on the use of herbal extracts to address women-centric disorders.

KR20110088814A from Korea University Research and Business Foundation titled Composition of Pueraris lobata extracts for menopausal symptoms describes a composition for improving women’s health during menopause, contains Pueraria lobata extract as an active ingredient for reducing body fat and blood neutral fat level and suppresses bone density loss and breast cancer risk ^[56].

CN103784497A titled Composition for improving bone and intestinal tract health of menopausal women and preparation method thereof, from Tiens Group, discloses a composition prepared from the raw materials comprising 1-200 parts of enzymolysis bone calcium, 5-50 parts of a radix puerariae extract, 10-100 parts of fructo oligosaccharide, 0-800 parts of honey, and 0-50 parts of sodium citrate for improving menopausal women bone and intestinal tract health ^[57].

KR20160135037A titled Compositions for preventing or treating metabolic disorders comprising an extract of Caragana Sinicafiled by Kyungpook National University-Industry-academic Co-op. Found describes composition comprising Caragana Sinica extract as an active ingredient for preventing and treating metabolic diseases in women after menopause, wherein such disorders are lipid and sugar metabolism, particularly dyslipidemia, hypertension, arteriosclerosis, hyperinsulinemia, diabetes and liver diseases i.e. fatty liver, steatohepatitis, and non-viral hepatitis ^[58].

Conclusion

With development of technology and people’s adaptation of the same, apps and various devices and are being used to address problems in women’s health. While a plethora of new technologies are being developed for women, there is still vast potential to create an impact on improving women’s health. Natural extracts are being used to address women’s health issues. While regulatory challenges can be expected, other limitations could be around high device costs, insufficient accurate data and unbiased clinical trials. If these impediments can be overcome, the implementation of new femtech resources will be faster.

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