Transient suppression of ovarian function Induced by Dulaglutide: a case report and review of the literature

Transient suppression of ovarian function Induced by Dulaglutide: a case report and review of the literature | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Transient suppression of ovarian function Induced by Dulaglutide: a case report and review of the literature Yangyang Guo, Mengchen Xie, Yuting Liu, Jinhui Huang, Qiong Wang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1698787/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Glucagon-like peptide-1 (GLP-1) agonist (GLP-1RA) is a new type of hypoglycemic agent with profound effects on the reproductive system. We report a case of ovarian function suppressed by the long-acting GLP-1RA dulaglutide. Case presentation A 41-year-old Chinese female presented with amenorrhea after treatment with GLP-1RA dulaglutide for type 2 diabetes. Her sex hormone measurement showed that the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were increased, while estradiol(E2) level was decreased. Her symptoms improved after the stoppage of dulaglutide. However, LH and FSH levels were still above the normal range two months after discontinuing the injection of dulaglutide. Conclusion The long-acting GLP-1RA dulaglutide may transiently suppress ovarian function. Because of their different structures and half-times, the individual impact on the reproductive system of each type of GLP-1RA should be monitored in the future. Dulaglutide Amenorrhea GLP- 1 receptor agonist (GLP-1 RA) ovary Background Glucagon-like peptide-1 (GLP-1) agonist (GLP-1RA) is a new kind of hypoglycemic agent, it improves both fasting and postprandial blood glucose concentrations in type2 diabetic (T2D) patients through multiple mechanisms, including glucose level dependently stimulating insulin secretion and inhibiting glucagon secretion, delaying gastric emptying[ 1 ]. Despite its hypoglycemic effect, GLP-1 has a profound impact on the reproductive system. It directly induces both hypothalamic kisspeptin expression and gonadotropin-releasing hormone (GnRH) secretion in vivo and vitro[ 2 ]. Indirectly, GLP-1RA altered sex hormone levels in both males and females through its insulin-sensitizing effect[ 3 ]. In addition, a case of male infertility induced by GLP-1RA liraglutide due to interrupted sperm production has been reported [ 3 ]. Here, we report a case of transient suppression of ovarian function by long-acting GLP-1RA dulaglutide. To our knowledge, there have been no similar cases reported in the literature. Our case suggests that the function of the reproductive system should be carefully monitored during the use of dulaglutide in the future. Case Presentation This is a 41-year-old Chinese female who has had T2D for six years without any complications. Her menarche was at 14, had regular menstruation of a 30-day cycle. She did not have a history of amenorrhea or other reproductive system-related disorders such as miscarriage and abnormal pregnancy. She had no family history of premature ovarian failure. She had a history of hyperlipidemia and took fenofibrate capsules of 200 mg QN. Her triglyceride level was controlled between 5 and 6mmol/L. She also had a history of hypertension for six years and took valsartan amlodipine fixed dosage tablets, one pill daily, and her blood pressure was well controlled. Initially, she managed with a single dose of liraglutide 1.2mg injected daily for three years, during which blood sugar control was not satisfied. Her fasting blood glucose (FBG) ranged from 7 to 8 mmol/L and her postprandial blood glucose(PBG) was between 12 and15 mmol/L, her menstrual was regular. She changed to a weekly injection of1.5mg dulaglutide one year ago for better blood glucose control, then her blood sugar control was stable and reached the target. Three months later, she lost 2.5 kg and was experiencing amenorrhea, hot flushes, sweating, and mental tiredness. Her sex hormone examination showed that the level of luteotropic hormone (LH) was 38.5mIU/mL (higher than the normal range), the level of follicle-stimulating hormone (FSH) was 62mIU/mL (higher than the normal range), and the level of estradiol(E2) was 32 ng/L. (lower than the normal range) (Table 1 ). We thus considered ovarian function inhibition according to the patient's sex hormone levels. Because amenorrhea occurred soon after the injection of dulaglutide, dulaglutide possibly induced the suppression of ovarian function, and this agent was discontinued. Table 1 Sex hormone level June 1st,2021 June 30th,2021 July 21st,2021 January 4th,2022 Reference range Estradiol(ng/L) 32 211 69 43 Follicular phase:24–114; Ovulation:62–534; Luteal phase:80–273; Menopause:3–88 Testosterone (ng/dL) 0.71 29.15 35.37 44.40 0.00–75.00 LH(mIU/mL) 38.50 18.47 5.11 9.80 Follicular phase:2.12–10.89; Ovulation:19.18-103.03; Luteal phase:1.2-12.86; Menopause:10.87–58.64 FSH(mIU/mL) 62.00 4.07 5.75 23.03 Follicular phase:3.85–8.78; Ovulation:4.54–22.51; Luteal phase:1.79–5.12; Menopause:16.74-113.59 Prolactin(ng/mL) 806.00 13.59 7.69 7.45 2.74–26.72 Progesterone(ng/mL) 0.797 0.29 0.13 0.16 Follicular phase:0.31–1.52; Ovulation:5.16–18.56; Menopause:0.08–0.78 Detection period Luteal phase Luteal phase Follicular phase Follicular phase One month later, her symptom of hot flushes improved. But menstruation was not presented. Gynecological sonography was performed, showing the thickness of the endometrium is about 1.1cm. Sex hormone test showed LH level was 18.47mIU/mL, FSH level was 4.07mIU/mL, E2 level was 211.0ng/L, prolactin (PRL) level was 13.59mIU/mL (Table 1 ). Two more weeks later, she restored menstruation. Sex hormone test showed that her LH level was 5.11mIU/mL, FSH level was 5.74 mIU/mL, and E2 level was 69.0ng/L (Table 1 ). Due to the satisfactory blood glucose control and convenience of use, the patient chose dulaglutide for diabetes therapy again two months later. Her menstruation was delayed for a month, and she was prescribed dydrogesterone 10mg bid due to her reluctance to discontinue dulaglutide. The sex hormones test three months later revealed LH level was 9.8mIU/mL, FSH level was 23.03mIU/mL, and E2 was 43.0ng/L (Table 1 ), with no visible abnormalities in gynecological ultrasonography. Table 1 . Sex hormone level Discussion In the present study, we report a case of transient suppression of ovarian function possibly induced by the GLP-1RA dulaglutide. To our knowledge, there were no similar cases reported in the literature. The age of the patient is a risk factor for ovarian hypofunction. In Chinese females, the average age of menopause is 48.2 years [ 4 ]. However, the high FSH and LH levels were not related to age, since she returned to normal FSH and LH levels and regular menstrual soon after quitting dulaglutide. Due to her blood glucose being well-controlled during the injection of dulaglutide, her ovarian hypofunction was not caused by diabetes. Long-term treatment with valsartan/amlodipine fixed-dose combination and fenofibrate has not been reported to cause ovarian hypofunction, but the literature review showed that fenofibrate protects against premature ovarian failure when used in conjunction with valsartan and amlodipine[ 5 ]. Weight reduction after dulaglutide injection may play a role in the aberrant sex hormone levels. Dulaglutide resulted in a weight loss of around 2.5 kg for the patient. It is difficult to differentiate if these changes are caused by weight loss, dulaglutide per se , or both. Some studies found that circulating LH and testosterone levels were decreased due to the gonadal axis HPG inhibited by short-term weight loss due to insufficient energy storage [ 6 – 9 ]. Therefore, the patient's elevated FSH and LH levels cannot be explained simply by weight reduction. The patient's reproductive system was not affected by liraglutide, but when she was injected with dulaglutide, her gonadotropin levels increased even though she was using contraceptives. However, after stopping treatment with dulaglutide, gonadotropin levels returned to normal. We thus conclude that dulaglutide was responsible for the temporary inhibition of ovarian function. Dulaglutide is a weekly injected long-acting GLP-1RA composed of an engineered GLP-1 covalently linked to a modified human IgG4-Fc heavy chain to decrease the rate of renal clearance. Unlike exenatide-based GLP-1RAs, dulaglutide shares 90% homology to human GLP-1[ 10 ]. The effect of GLP-1 receptor activation on gonadal hormone and its regulation was convoluted. The GLP-1 receptor co-localizes with kisspeptin in the hypothalamic arched nucleus[ 11 ]. GLP-1 directly induces GnRH and its regulator kisspeptin expression [ 12 ], and the central GLP-1 signal enhancement leads to a surge in preovulation LH in female rats[ 13 ], whereas GLP-1 receptor deficiency causes delayed puberty in female mice[ 14 ]. GLP-1 increases LH levels in male rats by promoting GnRH production in the hypothalamus[ 15 ]. After GLP-1 receptor activation, there is also a gender-biased GnRH secretion pattern: long-lasting LH secretion in male rats and brief LH spike in female rats, probably due to the sensitivity of kisspeptin neurons or the pituitary gland to GnRH in different gender. Liraglutide, a GLP-1 receptor agonist, has been proven in recent trials to treat reproductive abnormalities linked with obesity in both men and women[ 16 ]. A recent study revealed that liraglutide could stimulate ARC kiss-1 cells in brain slices, but it was insufficient to reverse LH suppression caused by negative energy balance in fasting rats [ 17 ].After long-term treatment with liraglutide, sex hormone levels increased in obese and hypogonadal men with or without diabetes[ 18 ]. Even though GLP-1 injections to healthy males did not alter mean reproductive hormone levels, they decreased testosterone pulses, suggesting that it has both metabolic and reproductive system effects. We hypothesize that because dulaglutide has a longer half-life than liraglutide, which keeps gonadotropin secretion stimulated but reduces its pulsatile, thus desensitizing the ovary to gonadotropin and preventing ovarian activity. Long-term infusion of kisspeptin-10 results in a significant increase in FSH in female rats, while LH gradually returns to normal after a transient increase, possibly explained by the long-term elevated kisspeptin input leading to changes in the GnRH release pattern in terms of frequency and pulse amplitude, and preferentially driving FSH secretion. Because the patient was only monitored for a year, it was impossible to predict whether long-term stimulation of dulaglutide would cause substantial atrophy of the ovaries and irreversible functional decline. Prolactin was likewise increased following dulaglutide injection in this case. This could be due to prolactin-releasing peptide (PrRP) neurons expressing GLP-1 receptors and are downstream of GLP-1 neurons in the caudal nucleus of the solitary tract in the dorsomedial hindbrain[ 19 ]. In conclusion, we reported a case of transient suppression of ovarian function possibly induced by long-acting GLP-1RA dulaglutide. It is important to evaluate the reproductive effects of each GLP-1RA in the future because of their various structures and half-times. Abbreviations GLP-1 glucagon-like peptide-1 T2D type-2 diabetic GnRH gonadotropin-releasing hormone LH luteotropic hormone PrRP prolactin-releasing peptide FSH follicle-stimulating hormone Declarations Acknowledgements The authors thank all the participants in this study. Authors’ contributions Y.G., J.H. M.X. contributed equally to this manuscript. Y.G., J.H. and X.W. contributed to data analysis, manuscript drafting and critical discussion. All authors have read and approved the manuscript. Funding Our work was supported by the Administration of Traditional Chinese Medicine of Jiangsu Province of China [grant number YB201917]. Availability of data and materials The datasets analyzed during the current study are available from the corresponding authors on reasonable request. Declarations Ethics approval and consent to participate This study was in accordance with the Helsinki declaration of 1975, as revised in 2008 and approved by Institutional Review Board (IRB) of the Affiliated Hospital of Nanjing University of Chinese Medicine. Written informed consent was obtained from all participants. Consent for publication Written informed consent was obtained from the patient and her family members for publication of this Case report and any accompanying images. Competing interests The authors declare that they have no conflict of interest. Author details Nanjing University Of Chinese Medicine, 210023 Nanjing, China. 1*.Jiangsu Province Hospital of TCM/the Affiliated Hospital of Nanjing University of Chinese Medicine, 210029 Nanjing, China. References Cornell S: A review of GLP-1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once-weekly agents . J CLIN PHARM THER 2020, 45 Suppl 1 :17–27. https://doi.org/10.1111/jcpt.13230 Heppner KM, Baquero AF, Bennett CM, Lindsley SR, Kirigiti MA, Bennett B, Bosch MA, Mercer AJ, Ronnekleiv OK, True C et al : GLP - 1R Signaling Directly Activates Arcuate Nucleus Kisspeptin Action in Brain Slices but Does not Rescue Luteinizing Hormone Inhibition in Ovariectomized Mice During Negative Energy Balance . eNeuro 2017, 4 (1). https://doi.org/10.1523/ENEURO.0198-16.2016 Fontoura P, Cardoso MC, Erthal-Martins MC, Werneck C, Sartorio C, Ramos CF: The effects of liraglutide on male fertility: a case report . REPROD BIOMED ONLINE 2014, 29 (5):644–646. https://doi.org/10.1016/j.rbmo.2014.07.009 Wang M, Gan W, Kartsonaki C, Guo Y, Lv J, Chen Z, Li L, Yang L, Yu M: Menopausal status , age at natural menopause and risk of diabetes in China : a 10 - year prospective study of 300 , 000 women . Nutr Metab (Lond) 2022, 19 (1):7.https://doi.org/0.1186/s12986-022-00643-x Abdelzaher WY, Abdel-Hafez S, Rofaeil RR, Ali A, Hegazy A, Bahaa HA: The protective effect of fenofibrate, triptorelin, and their combination against premature ovarian failure in rats . Naunyn Schmiedebergs Arch Pharmacol 2021, 394 (1):137–149. http://doi.org/10.1007/s00210-020-01975-2 Bergendahl M, Perheentupa A, Huhtaniemi I: Effect of short-term starvation on reproductive hormone gene expression, secretion and receptor levels in male rats . J ENDOCRINOL 1989, 121 (3):409–417. https://doi.org/10.1677/joe.0.1210409 Castellano JM, Navarro VM, Fernandez-Fernandez R, Nogueiras R, Tovar S, Roa J, Vazquez MJ, Vigo E, Casanueva FF, Aguilar E et al : Changes in hypothalamic KiSS-1 system and restoration of pubertal activation of the reproductive axis by kisspeptin in undernutrition . ENDOCRINOLOGY 2005, 146 (9):3917–3925. https://doi.org/10.1210/en.2005-0337 Chacon F, Cano P, Jimenez V, Cardinali DP, Marcos A, Esquifino AI: 24-hour changes in circulating prolactin, follicle-stimulating hormone, luteinizing hormone, and testosterone in young male rats subjected to calorie restriction . CHRONOBIOL INT 2004, 21 (3):393–404. https://doi.org/10.1081/CBI-120038607 Yang JA, Yasrebi A, Snyder M, Roepke TA: The interaction of fasting, caloric restriction, and diet-induced obesity with 17beta-estradiol on the expression of KNDy neuropeptides and their receptors in the female mouse . MOL CELL ENDOCRINOL 2016, 437 :35–50. http://doi.org/10.1016/j.mce.2016.08.008 Thompson AM, Trujillo JM: Dulaglutide: the newest GLP-1 receptor agonist for the management of type 2 diabetes . ANN PHARMACOTHER 2015, 49 (3):351–359. http://doi.org/10.1177/1060028014564180 Han SY, McLennan T, Czieselsky K, Herbison AE: Selective optogenetic activation of arcuate kisspeptin neurons generates pulsatile luteinizing hormone secretion . Proc Natl Acad Sci U S A 2015, 112 (42):13109–13114. http://doi.org/10.1073/pnas.1512243112 Oride A, Kanasaki H, Mijiddorj T, Sukhbaatar U, Hara T, Tumurbaatar T, Kyo S: GLP-1 increases Kiss-1 mRNA expression in kisspeptin-expressing neuronal cells . BIOL REPROD 2017, 97 (2):240–248. http://doi.org/10.1093/biolre/iox087 Outeirino-Iglesias V, Romani-Perez M, Gonzalez-Matias LC, Vigo E, Mallo F: GLP - 1 Increases Preovulatory LH Source and the Number of Mature Follicles , As Well As Synchronizing the Onset of Puberty in Female Rats . ENDOCRINOLOGY 2015, 156 (11):4226–4237. http://doi.org/10.1210/en.2014-1978 MacLusky NJ, Cook S, Scrocchi L, Shin J, Kim J, Vaccarino F, Asa SL, Drucker DJ: Neuroendocrine function and response to stress in mice with complete disruption of glucagon-like peptide-1 receptor signaling . ENDOCRINOLOGY 2000, 141 (2):752–762. http://doi.org/10.1210/endo.141.2.7326 Oride A, Kanasaki H, Mijiddorj T, Sukhbaatar U, Hara T, Tumurbaatar T, Kyo S: GLP-1 increases Kiss-1 mRNA expression in kisspeptin-expressing neuronal cells . BIOL REPROD 2017, 97 (2):240–248. http://doi.org/10.1093/biolre/iox087 Naderpoor N, Shorakae S, Joham A, Boyle J, De Courten B, Teede HJ: Obesity and polycystic ovary syndrome . MINERVA ENDOCRINOL 2015, 40 (1):37–51. Jensterle M, Janez A, Fliers E, DeVries JH, Vrtacnik-Bokal E, Siegelaar SE: The role of glucagon-like peptide-1 in reproduction: from physiology to therapeutic perspective . HUM REPROD UPDATE 2019, 25 (4):504–517. http://doi.org/10.1093/humupd/dmz019 Jensterle M, Podbregar A, Goricar K, Gregoric N, Janez A: Effects of liraglutide on obesity-associated functional hypogonadism in men . ENDOCR CONNECT 2019, 8 (3):195–202. http://doi.org/10.1530/EC-18-0514 Holt MK, Rinaman L: The role of nucleus of the solitary tract glucagon-like peptide-1 and prolactin-releasing peptide neurons in stress: anatomy, physiology and cellular interactions . Br J Pharmacol 2022, 179 (4):642–658. http://doi.org/10.1111/bph.15576 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1698787","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":109271684,"identity":"51686c84-0e3a-46aa-94f9-4124d993a2e2","order_by":0,"name":"Yangyang Guo","email":"","orcid":"","institution":"The Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yangyang","middleName":"","lastName":"Guo","suffix":""},{"id":109271685,"identity":"a41821d5-bafe-4e18-bd63-669d279f4143","order_by":1,"name":"Mengchen Xie","email":"","orcid":"","institution":"The Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mengchen","middleName":"","lastName":"Xie","suffix":""},{"id":109271686,"identity":"a49b9d46-7e64-4832-9230-9eed471883a0","order_by":2,"name":"Yuting Liu","email":"","orcid":"","institution":"The Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuting","middleName":"","lastName":"Liu","suffix":""},{"id":109271687,"identity":"73e90a08-01dd-4f98-82b6-537bb3e50c0d","order_by":3,"name":"Jinhui Huang","email":"","orcid":"","institution":"The Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jinhui","middleName":"","lastName":"Huang","suffix":""},{"id":109271688,"identity":"13990868-d3a8-4a68-9346-a6c651e51f1f","order_by":4,"name":"Qiong Wang","email":"","orcid":"","institution":"Jiangsu Province Hospital of Chinese Medicine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qiong","middleName":"","lastName":"Wang","suffix":""},{"id":109271689,"identity":"733e8f7e-872d-4b3c-96ed-bc094fa99dd4","order_by":5,"name":"Xin Wang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7ElEQVRIiWNgGAWjYBACg8NQBj8DQwKEdYBYLZINxGoBqoTqhaskpIWfnfcAM0/NHbvNtxueSfzMYZDju5HA+LkAjxY2Zr4EZp5jz5K33TmQJtm7jcFY8kYCs/QMvFp4DJhz2A4nm91ISJNm3MaQuOFGAlAQn8PAWv4dTjaeAdFST1CLZDNQS27bYTsDCYiWBANCWgwO8xgc/tt3OEHiRkKyZe82CcOZZx42S+PVcv6M4cMZ3w7b88/ISbzxc5uNPN/x5IOf8WkBgQNAnNjAwJMApCWAmLGBgAYIsGdgYD9AlMpRMApGwSgYeQAAvZJKW2xJRs4AAAAASUVORK5CYII=","orcid":"","institution":"The Affiliated Hospital of Nanjing University of Chinese Medicine","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Wang","suffix":""}],"badges":[],"createdAt":"2022-05-27 07:29:23","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1698787/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1698787/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22355102,"identity":"e68d255e-96ba-44af-a6c7-313fd306220f","added_by":"auto","created_at":"2022-06-07 13:59:32","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":654128,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1698787/v1/7fd89823-66af-48c2-a065-c5c2d33fa307.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Transient suppression of ovarian function Induced by Dulaglutide: a case report and review of the literature","fulltext":[{"header":"Background","content":"\u003cp\u003eGlucagon-like peptide-1 (GLP-1) agonist (GLP-1RA) is a new kind of hypoglycemic agent, it improves both fasting and postprandial blood glucose concentrations in type2 diabetic (T2D) patients through multiple mechanisms, including glucose level dependently stimulating insulin secretion and inhibiting glucagon secretion, delaying gastric emptying[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDespite its hypoglycemic effect, GLP-1 has a profound impact on the reproductive system. It directly induces both hypothalamic kisspeptin expression and gonadotropin-releasing hormone (GnRH) secretion in vivo and vitro[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Indirectly, GLP-1RA altered sex hormone levels in both males and females through its insulin-sensitizing effect[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In addition, a case of male infertility induced by GLP-1RA liraglutide due to interrupted sperm production has been reported [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we report a case of transient suppression of ovarian function by long-acting GLP-1RA dulaglutide. To our knowledge, there have been no similar cases reported in the literature. Our case suggests that the function of the reproductive system should be carefully monitored during the use of dulaglutide in the future.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eThis is a 41-year-old Chinese female who has had T2D for six years without any complications. Her menarche was at 14, had regular menstruation of a 30-day cycle. She did not have a history of amenorrhea or other reproductive system-related disorders such as miscarriage and abnormal pregnancy. She had no family history of premature ovarian failure. She had a history of hyperlipidemia and took fenofibrate capsules of 200 mg QN. Her triglyceride level was controlled between 5 and 6mmol/L. She also had a history of hypertension for six years and took valsartan amlodipine fixed dosage tablets, one pill daily, and her blood pressure was well controlled.\u003c/p\u003e \u003cp\u003eInitially, she managed with a single dose of liraglutide 1.2mg injected daily for three years, during which blood sugar control was not satisfied. Her fasting blood glucose (FBG) ranged from 7 to 8 mmol/L and her postprandial blood glucose(PBG) was between 12 and15 mmol/L, her menstrual was regular. She changed to a weekly injection of1.5mg dulaglutide one year ago for better blood glucose control, then her blood sugar control was stable and reached the target.\u003c/p\u003e \u003cp\u003eThree months later, she lost 2.5 kg and was experiencing amenorrhea, hot flushes, sweating, and mental tiredness. Her sex hormone examination showed that the level of luteotropic hormone (LH) was 38.5mIU/mL (higher than the normal range), the level of follicle-stimulating hormone (FSH) was 62mIU/mL (higher than the normal range), and the level of estradiol(E2) was 32 ng/L. (lower than the normal range) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). We thus considered ovarian function inhibition according to the patient's sex hormone levels. Because amenorrhea occurred soon after the injection of dulaglutide, dulaglutide possibly induced the suppression of ovarian function, and this agent was discontinued.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSex hormone level\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eJune 1st,2021\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eJune 30th,2021\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eJuly 21st,2021\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eJanuary\u003c/p\u003e \u003cp\u003e4th,2022\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eReference range\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEstradiol(ng/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e211\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFollicular phase:24\u0026ndash;114;\u003c/p\u003e \u003cp\u003eOvulation:62\u0026ndash;534;\u003c/p\u003e \u003cp\u003eLuteal phase:80\u0026ndash;273;\u003c/p\u003e \u003cp\u003eMenopause:3\u0026ndash;88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTestosterone (ng/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.71\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00\u0026ndash;75.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH(mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFollicular phase:2.12\u0026ndash;10.89;\u003c/p\u003e \u003cp\u003eOvulation:19.18-103.03;\u003c/p\u003e \u003cp\u003eLuteal phase:1.2-12.86;\u003c/p\u003e \u003cp\u003eMenopause:10.87\u0026ndash;58.64\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH(mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.07\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.03\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFollicular phase:3.85\u0026ndash;8.78;\u003c/p\u003e \u003cp\u003eOvulation:4.54\u0026ndash;22.51;\u003c/p\u003e \u003cp\u003eLuteal phase:1.79\u0026ndash;5.12;\u003c/p\u003e \u003cp\u003eMenopause:16.74-113.59\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProlactin(ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e806.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.74\u0026ndash;26.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgesterone(ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.797\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.29\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eFollicular phase:0.31\u0026ndash;1.52;\u003c/p\u003e \u003cp\u003eOvulation:5.16\u0026ndash;18.56;\u003c/p\u003e \u003cp\u003eMenopause:0.08\u0026ndash;0.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDetection period\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLuteal phase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLuteal phase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eFollicular phase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eFollicular phase\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eOne month later, her symptom of hot flushes improved. But menstruation was not presented. Gynecological sonography was performed, showing the thickness of the endometrium is about 1.1cm. Sex hormone test showed LH level was 18.47mIU/mL, FSH level was 4.07mIU/mL, E2 level was 211.0ng/L, prolactin (PRL) level was 13.59mIU/mL (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eTwo more weeks later, she restored menstruation. Sex hormone test showed that her LH level was 5.11mIU/mL, FSH level was 5.74 mIU/mL, and E2 level was 69.0ng/L (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDue to the satisfactory blood glucose control and convenience of use, the patient chose dulaglutide for diabetes therapy again two months later. Her menstruation was delayed for a month, and she was prescribed dydrogesterone 10mg bid due to her reluctance to discontinue dulaglutide. The sex hormones test three months later revealed LH level was 9.8mIU/mL, FSH level was 23.03mIU/mL, and E2 was 43.0ng/L (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), with no visible abnormalities in gynecological ultrasonography.\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Sex hormone level\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn the present study, we report a case of transient suppression of ovarian function possibly induced by the GLP-1RA dulaglutide. To our knowledge, there were no similar cases reported in the literature.\u003c/p\u003e \u003cp\u003eThe age of the patient is a risk factor for ovarian hypofunction. In Chinese females, the average age of menopause is 48.2 years [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the high FSH and LH levels were not related to age, since she returned to normal FSH and LH levels and regular menstrual soon after quitting dulaglutide. Due to her blood glucose being well-controlled during the injection of dulaglutide, her ovarian hypofunction was not caused by diabetes. Long-term treatment with valsartan/amlodipine fixed-dose combination and fenofibrate has not been reported to cause ovarian hypofunction, but the literature review showed that fenofibrate protects against premature ovarian failure when used in conjunction with valsartan and amlodipine[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWeight reduction after dulaglutide injection may play a role in the aberrant sex hormone levels. Dulaglutide resulted in a weight loss of around 2.5 kg for the patient. It is difficult to differentiate if these changes are caused by weight loss, dulaglutide \u003cem\u003eper se\u003c/em\u003e, or both. Some studies found that circulating LH and testosterone levels were decreased due to the gonadal axis HPG inhibited by short-term weight loss due to insufficient energy storage [\u003cspan additionalcitationids=\"CR7 CR8\" citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, the patient's elevated FSH and LH levels cannot be explained simply by weight reduction.\u003c/p\u003e \u003cp\u003eThe patient's reproductive system was not affected by liraglutide, but when she was injected with dulaglutide, her gonadotropin levels increased even though she was using contraceptives. However, after stopping treatment with dulaglutide, gonadotropin levels returned to normal. We thus conclude that dulaglutide was responsible for the temporary inhibition of ovarian function.\u003c/p\u003e \u003cp\u003eDulaglutide is a weekly injected long-acting GLP-1RA composed of an engineered GLP-1 covalently linked to a modified human IgG4-Fc heavy chain to decrease the rate of renal clearance. Unlike exenatide-based GLP-1RAs, dulaglutide shares 90% homology to human GLP-1[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe effect of GLP-1 receptor activation on gonadal hormone and its regulation was convoluted. The GLP-1 receptor co-localizes with kisspeptin in the hypothalamic arched nucleus[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. GLP-1 directly induces GnRH and its regulator kisspeptin expression [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and the central GLP-1 signal enhancement leads to a surge in preovulation LH in female rats[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], whereas GLP-1 receptor deficiency causes delayed puberty in female mice[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. GLP-1 increases LH levels in male rats by promoting GnRH production in the hypothalamus[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. After GLP-1 receptor activation, there is also a gender-biased GnRH secretion pattern: long-lasting LH secretion in male rats and brief LH spike in female rats, probably due to the sensitivity of kisspeptin neurons or the pituitary gland to GnRH in different gender.\u003c/p\u003e \u003cp\u003eLiraglutide, a GLP-1 receptor agonist, has been proven in recent trials to treat reproductive abnormalities linked with obesity in both men and women[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A recent study revealed that liraglutide could stimulate ARC kiss-1 cells in brain slices, but it was insufficient to reverse LH suppression caused by negative energy balance in fasting rats [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].After long-term treatment with liraglutide, sex hormone levels increased in obese and hypogonadal men with or without diabetes[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Even though GLP-1 injections to healthy males did not alter mean reproductive hormone levels, they decreased testosterone pulses, suggesting that it has both metabolic and reproductive system effects.\u003c/p\u003e \u003cp\u003eWe hypothesize that because dulaglutide has a longer half-life than liraglutide, which keeps gonadotropin secretion stimulated but reduces its pulsatile, thus desensitizing the ovary to gonadotropin and preventing ovarian activity. Long-term infusion of kisspeptin-10 results in a significant increase in FSH in female rats, while LH gradually returns to normal after a transient increase, possibly explained by the long-term elevated kisspeptin input leading to changes in the GnRH release pattern in terms of frequency and pulse amplitude, and preferentially driving FSH secretion. Because the patient was only monitored for a year, it was impossible to predict whether long-term stimulation of dulaglutide would cause substantial atrophy of the ovaries and irreversible functional decline.\u003c/p\u003e \u003cp\u003eProlactin was likewise increased following dulaglutide injection in this case. This could be due to prolactin-releasing peptide (PrRP) neurons expressing GLP-1 receptors and are downstream of GLP-1 neurons in the caudal nucleus of the solitary tract in the dorsomedial hindbrain[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn conclusion, we reported a case of transient suppression of ovarian function possibly induced by long-acting GLP-1RA dulaglutide. It is important to evaluate the reproductive effects of each GLP-1RA in the future because of their various structures and half-times.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGLP-1\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eglucagon-like peptide-1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eT2D\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etype-2 diabetic\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eGnRH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egonadotropin-releasing hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eLH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eluteotropic hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePrRP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eprolactin-releasing peptide\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFSH\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003efollicle-stimulating hormone\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank all the participants in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eY.G., J.H. M.X. contributed equally to this manuscript. Y.G., J.H. and X.W. contributed to data analysis, manuscript drafting and critical discussion. All authors have read and approved the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur work was supported by the Administration of Traditional Chinese Medicine of Jiangsu Province of China [grant number YB201917].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets analyzed during the current study are available from the corresponding authors on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis study was in accordance with the Helsinki declaration of 1975, as revised in 2008 and approved by Institutional Review Board (IRB) of the Affiliated Hospital of Nanjing University of Chinese Medicine. Written informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient and her family members for publication of this Case report and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n\u003cli\u003eNanjing University Of Chinese Medicine, 210023 Nanjing, China.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e1*.Jiangsu Province Hospital of TCM/the Affiliated Hospital of Nanjing University of Chinese Medicine, 210029 Nanjing, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCornell S: \u003cb\u003eA review of GLP-1 receptor agonists in type 2 diabetes: A focus on the mechanism of action of once-weekly agents\u003c/b\u003e. 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Br J Pharmacol 2022, \u003cb\u003e179\u003c/b\u003e(4):642\u0026ndash;658.\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttp://doi.org/10.1111/bph.15576\u003c/span\u003e\u003cspan address=\"10.1111/bph.15576\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Dulaglutide, Amenorrhea, GLP- 1 receptor agonist (GLP-1 RA), ovary ","lastPublishedDoi":"10.21203/rs.3.rs-1698787/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1698787/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\u003cp\u003eGlucagon-like peptide-1 (GLP-1) agonist (GLP-1RA) is a new type of hypoglycemic agent with profound effects on the reproductive system. We report a case of ovarian function suppressed by the long-acting GLP-1RA dulaglutide.\u003c/p\u003e\u003cp\u003eCase presentation\u003c/p\u003e\u003cp\u003eA 41-year-old Chinese female presented with amenorrhea after treatment with GLP-1RA dulaglutide for type 2 diabetes. Her sex hormone measurement showed that the levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were increased, while estradiol(E2) level was decreased. Her symptoms improved after the stoppage of dulaglutide. However, LH and FSH levels were still above the normal range two months after discontinuing the injection of dulaglutide.\u003c/p\u003e\u003cp\u003eConclusion\u003c/p\u003e\u003cp\u003eThe long-acting GLP-1RA dulaglutide may transiently suppress ovarian function. Because of their different structures and half-times, the individual impact on the reproductive system of each type of GLP-1RA should be monitored in the future.\u003c/p\u003e","manuscriptTitle":"Transient suppression of ovarian function Induced by Dulaglutide: a case report and review of the literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-05-31 21:57:09","doi":"10.21203/rs.3.rs-1698787/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"37c3c928-5360-43fd-af91-f0f8e70f80fb","owner":[],"postedDate":"May 31st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2022-06-07T13:59:27+00:00","versionOfRecord":[],"versionCreatedAt":"2022-05-31 21:57:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1698787","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1698787","identity":"rs-1698787","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}