{"componentChunkName":"component---src-components-article-page-article-page-gatsby-container-tsx","path":"/articles/cycle-a-z/the-case-for-a-new-pcos-therapy","result":{"data":{"articleNode":{"id":"3XKAAUpOWsi8qSM4wKwiuA","title":"The case for a new PCOS therapy","subtitle":"I’ve been treating patients with PCOS for 40 years. Here is my approach.","seoMetaTitle":"PCOS Treatment: Addressing a Root Cause","seoMetaDescription":"I’ve been treating patients with PCOS for 40 years. Here is my approach.","openGraphTitle":"The case for a new PCOS therapy","openGraphDescription":"I’ve been treating patients with PCOS for 40 years. Here is my approach.","slug":"cycle-a-z/the-case-for-a-new-pcos-therapy","artCredits":"Illustration by Emma Günther","publishDate":"2018-11-29T00:00+01:00","updatedAt":"2021-12-06T12:53:22.472Z","createdAt":"2018-11-29T10:45:55.280Z","locale":"en","authors":[{"id":"1KzvY1bbyA8KS4uUmYA6Gm","name":"Jerilynn C. Prior MD, FRCPC","headline":"Contributor","slug":"jerilynn-c-prior-md-frcpc","twitter":null,"locale":"en","profileImage":{"id":"oTPavRpcliKkqM0QiuWuE","description":"","file":{"contentType":"image/jpeg","url":"//images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg"},"gatsbyImageData":{"images":{"sources":[{"srcSet":"https://images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg?w=300&h=300&q=50&fm=webp 300w,\nhttps://images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg?w=600&h=600&q=50&fm=webp 600w,\nhttps://images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg?w=1200&h=1200&q=50&fm=webp 1200w","sizes":"(min-width: 1200px) 1200px, 100vw","type":"image/webp"}],"fallback":{"src":"https://images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg?w=1200&h=1200&fl=progressive&q=50&fm=jpg","srcSet":"https://images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg?w=300&h=300&fl=progressive&q=50&fm=jpg 300w,\nhttps://images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg?w=600&h=600&fl=progressive&q=50&fm=jpg 600w,\nhttps://images.ctfassets.net/juauvlea4rbf/oTPavRpcliKkqM0QiuWuE/c951309511c6917198502673c6170725/author_Jerilynn_2x-100.jpg?w=1200&h=1200&fl=progressive&q=50&fm=jpg 1200w","sizes":"(min-width: 1200px) 1200px, 100vw"}},"layout":"constrained","backgroundColor":"#88b888","width":1200,"height":1200}}}],"reviewers":null,"editors":null,"featuredImage":{"description":"","file":{"contentType":"image/png","url":"//images.ctfassets.net/juauvlea4rbf/5uzFOGXmGbSoGuMueA4nj/730aadc70c94b57175667cb05cce6c53/Contentful__2_.png"},"gatsbyImageData":{"images":{"sources":[{"srcSet":"https://images.ctfassets.net/juauvlea4rbf/5uzFOGXmGbSoGuMueA4nj/730aadc70c94b57175667cb05cce6c53/Contentful__2_.png?w=240&h=120&q=50&fm=webp 240w,\nhttps://images.ctfassets.net/juauvlea4rbf/5uzFOGXmGbSoGuMueA4nj/730aadc70c94b57175667cb05cce6c53/Contentful__2_.png?w=480&h=240&q=50&fm=webp 480w,\nhttps://images.ctfassets.net/juauvlea4rbf/5uzFOGXmGbSoGuMueA4nj/730aadc70c94b57175667cb05cce6c53/Contentful__2_.png?w=960&h=480&q=50&fm=webp 960w,\nhttps://images.ctfassets.net/juauvlea4rbf/5uzFOGXmGbSoGuMueA4nj/730aadc70c94b57175667cb05cce6c53/Contentful__2_.png?w=1920&h=960&q=50&fm=webp 1920w","sizes":"(min-width: 960px) 960px, 100vw","type":"image/webp"}]},"layout":"constrained","backgroundColor":"#88c8d8","width":960,"height":480}},"openGraphImage":{"description":"","file":{"url":"//images.ctfassets.net/juauvlea4rbf/54wYfOE0wrfX8TrqR65vqY/aeee271a0fcd73c82a172e1e9b4d24c4/FB__24_.png"}},"sectionDivider":null,"featuredVideoURL":null,"category":{"id":"6r6NC5Oyq93sE3gE9U7n5a","slug":"pcos","title":"PCOS","color":null,"description":{"description":"Articles about Polycystic Ovary Syndrome."},"parentCategory":{"title":"Issues & Conditions","slug":"issues-and-conditions"},"locale":"en"},"body":{"body":"For more than 40 years, I’ve been trying to figure out the root cause of PCOS. \n\nThe causes of [Polycystic Ovary Syndrome (PCOS)](https://helloclue.com/articles/cycle-a-z/what-you-may-not-know-about-pcos-questions-and-misconceptions) (or Anovulatory Androgen Excess, AAE, as we call it at the Centre for Menstrual Cycle and Ovulation Research) continue to be mysterious (1), though it appears to be related to both genetic and environmental factors. \n\nLooking for the physiological causes of the syndrome is a bit like the proverb of the blind women and the elephant: one woman stands by the elephant’s rump and says, “An elephant is like a rope” as she feels the tail. Another reports, “An elephant is like a tree” as she pats the elephant’s leg. Different PCOS experts are similar—some specialize in [blood sugars and insulin](https://helloclue.com/articles/cycle-a-z/the-link-between-pcos-and-insulin-resistance), seeing PCOS primarily as a risk for diabetes and obesity. Others are skin experts and see the skin oiliness, acne, and [unwanted facial and body hair](https://helloclue.com/articles/cycle-a-z/hirsutism-and-the-menstrual-cycle) typical of PCOS. \n\nOn the other hand, as someone specializing in hormones and glands, I seek to understand the “whole elephant”—all of the changes that characterize the experiences of PCOS in whole populations of women.\n\n## How I treat PCOS\nI’ve come to suspect that an underlying mechanism of PCOS is that a hormone called gonadotropin releasing hormone (GnRH) is being released from the brain too rapidly, in quicker than normal pulses. This leads to rapid bursts of another hormone being produced in the pituitary gland (a small hormone producing gland at the base of the brain), called *luteinizing hormone* (LH)(2). In my practice, I’ve seen repeated cases where women with PCOS exhibit rapid LH pulses. Too much LH can stimulate higher levels of both androgens (including testosterone) and estrogens to be produced, which interfere with [ovulation](https://helloclue.com/articles/cycle-a-z/ovulation-101-what-is-it-how-does-it-work) and the menstrual cycle. My theory is that it is possible to treat PCOS by directly addressing this rapid GnRH hormonal pulsing.\n\n### PCOS treatment: a case study \nIn the early 1980s, a 30-year-old woman came to my office who had only 2 to 3 menstrual periods each year. She had borderline diabetes, a high BMI, and was struggling with facial hair. Her reproductive hormonal levels not normal: she had high estrogen but was not making her own progesterone, as she wasn’t ovulating. I prescribed oral micronized progesterone to be taken for 14 days then stopped for 14 days, repeatedly. When I saw her again about two months later, she had experienced two regular, normal-length menstrual cycles. \n\nI asked her how she felt—she said “I feel more like myself.” She had lost weight and, because she felt better, had started walking regularly.  She was still very concerned, however, about needing to wash her hair every third day to prevent oiliness and having to shave the dark hair on her chin regularly.\n\nI decided to ask her to try the medication *spironolactone*. Spironolactone is sometimes used for high blood pressure or heart failure, and has the action of blocking the way testosterone works (and thus preventing the testosterone from stimulating the growth of dark facial hair and oil production in skin glands) (3). Unlike the other major anti-androgen (*cyproterone acetate*), spironolactone is safe and has no serious side effects in women. It can cause abnormal bleeding in women when not taken with cyclic progesterone, but that wasn’t an issue. It can also be risky for a male fetus were she to accidentally get pregnant, so she should be sure to use a non-hormonal contraceptive. She agreed and began taking the spironolactone with her progesterone.\n\nShe continued to have regular periods and had lost more weight by the time I saw her six months later; now she was no longer overweight. I instructed her to take her progesterone during the second half of her menstrual cycle (the luteal phase) on cycle days 14-27 (when she didn’t have a cycle at all, she had been doing two weeks on, two weeks off). She was thrilled that now she could “get away with” washing her hair every five days and said her chin hair felt less coarse and was lighter in color. \nA year later she continued to have regular periods on the combined medication. Her tests for diabetes were normal, and she rarely shaved her face anymore and could easily pluck the few remaining darker hairs. Several months after that, she no longer had oily skin and hair, and had only a few soft yellow hairs on her face. I tested her to see if she was ovulating, and making her own progesterone. She was, and we stopped the spironolactone at that point. \n\nSoon after, she said she [wished to become pregnant](https://helloclue.com/articles/cycle-a-z/pcos-and-pregnancy) and asked me if I thought she could now try for pregnancy. She was still taking progesterone during her luteal phase, and at this point I instructed her to start doing LH urine tests to make sure she wasn’t taking the progesterone until she had truly ovulated, since this can interfere with a pregnancy (and the timing of ovulation can vary). We decided that she would continue to take progesterone for 14 days every cycle but delay the start until after she saw and LH peak from her urine test—women with PCOS who haven’t been ovulating regularly often lower progesterone production, which is not optimal for fertility (4). Plus, taking progesterone is associated with increased chances of having a successful pregnancy in people who have a history of [miscarriage](https://helloclue.com/articles/life-stages/miscarriage-its-more-common-than-you-think) (5). About eight months later, she had a healthy birth.\n\nI subsequently saw many women with PCOS whom I treated the same way and whose troubles with weight loss, infrequent periods, subfertility, and unwanted facial hair eventually disappeared—these are the four main concerns that women with PCOS report (6). \n\n## It’s time to look into new treatments\nProgesterone slows the midcycle pulses of LH (and GnRH), that are too rapid in people with PCOS (2). Taking cyclic progesterone when the body isn’t producing its own (due to lack of ovulation) makes the LH pulses slow down. High testosterone interferes with progesterone’s ability to slow the LH pulses, so adding spironolacone to treatment lowers testosterone levels and prevents this from happening—LH pulses are then regulated, along with the menstrual cycle and its functions.\n\nI’ve since tried several times to obtain funding to do the observational and then randomized controlled trials to test this innovative PCOS therapy; so far I’ve not had success. I believe it is well past time to properly test cyclic progesterone with spironolactone for women with PCOS (as long as they are willing to take a non-hormonal form of contraception while taking spironolactone). I hope you agree. \n\n__Track your PCOS symptoms. [Download Clue](https://helloclue.com/period-tracker-app) today.__\n  \n\n\n"},"bodyRichText":null,"references":{"references":"1. Prior JC, Kalyan S, Seifert-Klauss V. Re-naming pcos - suggest anovulatory androgen excess. JCEM . 2014. Letter to the editor\n2. Blank SK, McCartney CR, Marshall JC. The origins and sequelae of abnormal neuroendocrine function in polycystic ovary syndrome. Hum Reprod Update 2006;12(4):351-361.\n3. Prior JC, Vigna YM, Watson D. Spironolactone with physiological female gonadal steroids in the presurgical therapy of male to female transsexuals: a new observation. Arch Sex Beh 1989;18:49-57.\n4. Joseph-Horne R, Mason H, Batty S et al. Luteal phase progesterone excretion in ovulatory women with polycystic ovaries. Hum Reprod 2002;17(6):1459-1463.\n5. Stephenson MD, McQueen D, Winter M, Kliman HJ. Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss. Fertil Steril 2017;107(3):684-690.\n6. Gibson-Helm M, Teede H, Dunaif A, Dokras A. Delayed Diagnosis and a Lack of Information Associated With Dissatisfaction in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab 2017;102(2):604-612.\n"},"partnerships":null,"relatedArticles":null,"articleFooterDownloadWidgetText":null},"recommendedArticles":{"edges":[{"node":{"id":"2PwIEAWmS4Yg6c4iwmEsKM","title":"PCOS and pregnancy","slug":"cycle-a-z/pcos-and-pregnancy","snippet":"Getting pregnant when you have PCOS can be a challenge, but treatments are available to help.","locale":"en","publishDate":"2018-08-23T00:00-04:00","authors":[{"id":"3Iyv4eECg0QEAakqKCoKQC","name":"Laurie Ray, DNP","headline":"Science Writer at Clue","slug":"laurie-ray","twitter":null,"locale":"en","profileImage":{"id":"1pX0hDtDeo0CiA2KY02kqS","description":"Laurie Ray","file":{"contentType":"image/jpeg","url":"//images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg"},"gatsbyImageData":{"images":{"sources":[{"srcSet":"https://images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg?w=300&h=300&q=50&fm=webp 300w,\nhttps://images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg?w=600&h=600&q=50&fm=webp 600w,\nhttps://images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg?w=1200&h=1200&q=50&fm=webp 1200w","sizes":"(min-width: 1200px) 1200px, 100vw","type":"image/webp"}],"fallback":{"src":"https://images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg?w=1200&h=1200&fl=progressive&q=50&fm=jpg","srcSet":"https://images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg?w=300&h=300&fl=progressive&q=50&fm=jpg 300w,\nhttps://images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg?w=600&h=600&fl=progressive&q=50&fm=jpg 600w,\nhttps://images.ctfassets.net/juauvlea4rbf/1pX0hDtDeo0CiA2KY02kqS/073adc748e3e40cff4c0977227196128/author_Laurie_2x-80.jpg?w=1200&h=1200&fl=progressive&q=50&fm=jpg 1200w","sizes":"(min-width: 1200px) 1200px, 100vw"}},"layout":"constrained","backgroundColor":"#080808","width":1200,"height":1200}}}],"featuredImage":{"description":"Someone holding an ovulation test, looking down on result.","file":{"url":"//images.ctfassets.net/juauvlea4rbf/38P3IK310saQ4GMeKQu06s/9af56097cbf08e9017175da23347cc61/PCOS_trying_to_conceive_contenful.svg","contentType":"image/svg+xml"},"gatsbyImageData":null},"category":{"title":"PCOS","slug":"pcos","color":null,"locale":"en"}}},{"node":{"id":"1lEAb6QfDuqI6kUiuA4Uu6","title":"Polycystic Ovary Syndrome (PCOS) 101","slug":"cycle-a-z/polycystic-ovary-syndrome-pcos-101","snippet":"PCOS is a common disorder, but it remains undiagnosed and unmanaged in most people who have it","locale":"en","publishDate":"2024-09-10T00:00+02:00","authors":[{"id":"53XXDZWUHSYKw4IQukGcG","name":"Anna Druet, BA","headline":"Science writer","slug":"anna-druet","twitter":null,"locale":"en","profileImage":{"id":"hOkf6TtNjqK8cwKY6uk0O","description":"portrait of anna druet","file":{"contentType":"image/png","url":"//images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png"},"gatsbyImageData":{"images":{"sources":[{"srcSet":"https://images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png?w=225&h=225&q=50&fm=webp 225w,\nhttps://images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png?w=450&h=450&q=50&fm=webp 450w,\nhttps://images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png?w=900&h=900&q=50&fm=webp 900w","sizes":"(min-width: 900px) 900px, 100vw","type":"image/webp"}],"fallback":{"src":"https://images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png?w=900&h=900&q=50&fm=png","srcSet":"https://images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png?w=225&h=225&q=50&fm=png 225w,\nhttps://images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png?w=450&h=450&q=50&fm=png 450w,\nhttps://images.ctfassets.net/juauvlea4rbf/hOkf6TtNjqK8cwKY6uk0O/968784f20b401b7217442fc6a0ce54a4/Anna_Druet.png?w=900&h=900&q=50&fm=png 900w","sizes":"(min-width: 900px) 900px, 100vw"}},"layout":"constrained","backgroundColor":"#f8f8f8","width":900,"height":900}}}],"featuredImage":{"description":"An illustration of a uterus, fallopian tubes and ovaries. 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