What to do if you have “polycysts”? New drug launched - Veozah reduces total testosterone by up to 33%!

Can women with polycystic disease still have children? Current domestic surveys show that the rate of polycystic ovary syndrome among women of childbearing age aged 18 to 45 is as high as 5.61%. As a new drug for the treatment of polycystic cysts, how effective is VEOZAH? Let’s take a look!

Polycystic ovary syndrome (PCOS)

In 1935, Stein and Leventhal classified amenorrhea, hirsutism, obesity and infertility into four major diseases, which they called Stein-Leventhal syndrome (S-L syndrome). In 1960, it was renamed polycystic ovary syndrome (PCOS) because the patient was characterized by cystic enlargement of both ovaries.

Polycystic ovary syndrome (PCOS), also known as "polycystic", is a highly common endocrine disease and the main cause of anovulatory infertility. It is characterized by chronic anovulation (disorder or loss of ovulation) and hyperandrogenism (excess production of male hormones in women). The main clinical manifestations are irregular menstrual cycles, infertility, hirsutism and acne. It is the most common female endocrine disease. 

Normally, there is a balance between estrogen and neurokinin B (NKB) in healthy women. When estrogen decreases, the balance is disrupted. This balance regulation is located in the body's temperature-regulating center in specific areas of the brain. Therefore, polycystic ovary syndrome can be treated by regulating neurokinin B, which blocks the thermoregulatory center, to help restore balance.

What kind of medicine is Veozah?

Astellas announced on May 12 that the U.S. Food and Drug Administration (FDA) has approved Veozah (fezolinetant) for the treatment of moderate to severe vasomotor symptoms (VMS) caused by menopause, also known as hot flashes. Veozah is the first neurokinin 3 (NK3) receptor antagonist approved by the FDA to treat these patients. In addition, Veozah can also treat polycystic ovary syndrome in women.

So, how does VEOZAH work? Research shows that VEOZAH can regulate the neural activity of the brain's temperature regulation center (hypothalamus) by blocking the combination of neurokinin B and neurokinin B nerves, thereby restoring the balance between estrogen and neurokinin B and achieving the effect of treating polycystic ovary syndrome in women.

How effective is Veozah?

In August 2021, "J Clin Endocrinol Metab" published a phase II, randomized, double-blind, placebo-controlled trial study to evaluate the clinical efficacy of the neurokinin 3 (NK3) receptor antagonist fezolinetant in patients with polycystic ovary syndrome. The primary efficacy endpoint was change in total testosterone from baseline to week 12. The secondary efficacy endpoint was the ratio of luteinizing hormone to follicle-stimulating hormone.

A total of 73 patients were recruited and randomly assigned in a 1:1:1 ratio to receive fezolinetant 60 mg, 180 mg, or placebo, of which 64 participants completed the trial. The patients were clinically evaluated every 3 weeks and attended follow-up visits 6 weeks after completion of treatment.

At 3, 6 and 12 weeks, the changes in total testosterone compared with baseline, the data of each group are mainly as follows: the changes in total testosterone in the 60 mg group decreased by 19%, 14% and 17% respectively; the changes in total testosterone in the 180 mg group decreased by 32%, 31% and 33% respectively; the changes in total testosterone in the placebo group decreased by 3%, 1% and 1% respectively. At week 9, total testosterone decreased by 8% from baseline in the 60 mg group and by 24% in the 180 mg group. Detailed data is shown in Figure A:

Figure A: Comparative changes in total testosterone in the three groups compared with baseline

Both 60 mg and 180 mg of fezolinetant significantly reduced the luteinizing hormone to follicle-stimulating hormone ratio relative to placebo. In week 12. The reduction in the ratio of luteinizing hormone and follicle-stimulating hormone also had a sustained effect, and the fezolinetant 180mg group had a better maintenance effect. Details are shown in Figure B:

Figure B: Ratios of luteinizing hormone and follicle-stimulating hormone in three groups

Therefore, fezolinetant can effectively reduce total testosterone levels in patients with polycystic ovary syndrome, especially in the 180 mg group, which can reduce it by up to 33%. In addition, fezolinetan also significantly and consistently reduced the luteinizing hormone to follicle-stimulating hormone ratio relative to placebo.

In summary, the clinical efficacy of fezolinetant in patients with polycystic ovary syndrome is very impressive!

Global research and development of polycystic ovary syndrome drugs

Currently, there are 31 drugs for polycystic ovary syndrome, in addition to Veozah, which is already on the market. There are 16 drugs currently in the non-development stage, 5 drugs in the preclinical stage, 1 drug in the clinical application stage, 2 drugs in the clinical phase 1 stage, 1 drug in the clinical phase 1/2, 4 drugs in the clinical phase 2, and 4 drugs in the clinical phase 3. In addition, there is another drug that has appeared in front of you. Today I will briefly introduce it to you:

Gonadorelin acetate

In January 1989, Gonadorelin Acetate was approved for marketing in Japan for the treatment of endometriosis, polycystic ovary syndrome and prostatic hyperplasia.

Gonadorelin acetate is an effective progesterone-releasing hormone inhibin receptor antagonist, used to control ovarian stimulation to prevent premature discharge of immature follicles and help conception. Because gonadorelin acetate is easily decomposed and destroyed by enzymes in the gastrointestinal tract and cannot be used orally, it is often used as an injectable gonadorelin preparation, which is absorbed through subcutaneous or intramuscular injection and takes effect quickly.

"It's great that this product is coming to market," said Dr. Beth Prairie, an obstetrician-gynecologist and preventive medicine physician at Allegheny Health Network Midlife Women's Associates and chief medical officer at West Penn Hospital. Dr. Prairie, who has specialized in menopausal medications for more than 15 years, said Veozah's approval will open up a whole new possibility for patients who don't benefit from hormone therapy.

Dr. Beth Prairie, obstetrician, gynecologist and preventive medicine physician at the Middle Age Women's Association and chief medical officer of Western Pennsylvania Hospital. The image is from Google. Infringement will be deleted.

References

[1]Fraser GL, Obermayer-Pietsch B, Laven J, Griesinger G, Pintiaux A, Timmerman D, Fauser BCJM, Lademacher C, Combalbert J, Hoveyda HR, Ramael S. Randomized Controlled Trial of Neurokinin 3 Receptor Antagonist Fezolinetant for Treatment of Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2021 Aug 18;106(9):e3519-e3532. doi: 10.1210/clinem/dgab320. PMID: 34000049; PMCID: PMC8372662.

[2]Duncan WC. A guide to understanding polycystic ovary syndrome (PCOS). J Fam Plann Reprod Health Care.2014;40(3):217-225.

[3]Bozdag G, Mumusoglu S, Zengin D, Karabulut E, Yildiz BO. The prevalence and phenotypic features of polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod. 2016;31(12):2841-2855.