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01.11.2023 | Original Article

Effects of long-term proton pump inhibitor use on sexual hormones and sexual and reproductive health in female patients

verfasst von: Muhammad Ashfaq, Qasim Khan, Muhammad Zeeshan Haroon, Syed Mobasher Ali Abid, Muhammad Junaid Hassan Sharif, Yasser M. S. A. Alkahraman

Erschienen in: Endocrine | Ausgabe 2/2024

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Abstract

Purpose

Proton pump inhibitors (PPIs) are widely used to treat a range of gastrointestinal diseases around the world. Long-term use of PPIs has been associated to a variety of undesirable effects. Although short-term therapy has been shown to have little or no effect on endocrine hormone in women, however, its long-term safety has received little attention. We aimed at evaluating long-term use of PPIs and its effects on female reproductive hormones as well as related clinical consequences.

Methods

A cross-sectional study was conducted in two outpatient gastroenterology clinics in the province of Khyber Pakhtunkhwa. This study included female patients who had been using PPIs on a regular basis for 3 months or more.

Results

In total of 101 participants, patients with sexual complaints have significantly altered levels of prolactin (p = 0.05), estrogen (p < 0.001) and progesterone (p = 0.001) than patient without sexual complaints. The frequency of amenorrhea (p < 0.001), cyclic disturbances (p < 0.001), breast augmentation (p = 0.001) and painful breast (p = 0.004) were statistically significant in patients with raised serum prolactin values. Serum values of Sex hormone binding globulin SHBG (p < 0.001), estradiol (p = 0.002) and total testosterone (p < 0.001) were significantly altered between normal prolactin and hyperprolactinemic patients.

Conclusion

These findings suggest that long-term PPI use may cause endocrine hormone disturbances leading to sexual difficulties in women.

M. Jaynes, A.B. Kumar, The risks of long-term use of proton pump inhibitors: a critical review. Ther. Adv. Drug Saf. 2019;10:2042098618809927. https://doi.org/10.1177/2042098618809927

L.-Y. Yu, L.-N. Sun, X.-H. Zhang, Y.-Q. Li, L. Yu, Z.-Q.-Y. Yuan et al. A Review of the Novel Application and Potential Adverse Effects of Proton Pump Inhibitors. Adv. Ther. 34, 1070–1086 (2017). https://doi.org/10.1007/s12325-017-0532-9CrossRefPubMedPubMedCentral

M. Coulson, G.G. Gibson, N. Plant, T. Hammond, M. Graham, Lansoprazole increases testosterone metabolism and clearance in male Sprague-Dawley rats: implications for Leydig cell carcinogenesis. Toxicol. Appl. Pharm. 192, 154–163 (2003). https://doi.org/10.1016/s0041-008x(03)00275-8CrossRef

I. Thanoon, A. Mahmood, Effect of omeprazole on reproductive hormonal levels and sexual function in male patients with peptic ulcer disease. Al-Qadisiyah Med. J. 7, 190–198 (2011)CrossRef

H.G. Dammann, F. Burkhardt, N. Wolf, The effects of oral rabeprazole on endocrine and gastric secretory function in healthy volunteers. Aliment Pharm. Ther. 13, 1195–1203 (1999). https://doi.org/10.1046/j.1365-2036.1999.00545.xCrossRef

B. He, B. Carleton, M. Etminan, Risk of Gynecomastia with Users of Proton Pump Inhibitors. Pharmacotherapy 39, 614–618 (2019). https://doi.org/10.1002/phar.2245CrossRefPubMed

I.R. Daniels, G.T. Layer, How should gynaecomastia be managed? ANZ J. Surg. 73, 213–216 (2003). https://doi.org/10.1046/j.1445-1433.2002.02584.xCrossRefPubMed

K. Skałacka, R. Gerymski, Sexual activity and life satisfaction in older adults. Psychogeriatr. J. Jpn Psychogeriatr. Soc. 19, 195–201 (2019). https://doi.org/10.1111/psyg.12381CrossRef

A.A. Roman Lay, Y.A. de Oliveira Duarte, L.S. Duarte, A.L. Vilela Borges, Sexual activity and satisfaction in older adults from a Brazilian cohort study. Aging Ment. Health 27, 417–424 (2023). https://doi.org/10.1080/13607863.2021.2025338CrossRefPubMed

10.

R. Arya, B. Antonisamy, S. Kumar, Sample size estimation in prevalence studies. Indian J. Pediatr. 79, 1482–1488 (2012). https://doi.org/10.1007/s12098-012-0763-3CrossRefPubMed

11.

WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy. Geneva: World Health Organization. (2010) https://www.ncbi.nlm.nih.gov/books/NBK138650/

12.

M. Stentagg, L. Skär, J.S. Berglund, T. Lindberg, Cross-Sectional Study of Sexual Activity and Satisfaction Among Older Adult’s ≥60 Years of Age. Sex. Med. 9, 100316 (2021). https://doi.org/10.1016/j.esxm.2020.100316CrossRefPubMedPubMedCentral

13.

N. Beckman, M. Waern, D. Gustafson, I. Skoog, Secular trends in self reported sexual activity and satisfaction in Swedish 70 year olds: cross sectional survey of four populations, 1971-2001. BMJ 337, 151–154 (2008). https://doi.org/10.1136/bmj.a279CrossRefPubMedCentral

14.

Monash University. Female sexuality and changes with age. Public Health Prev Med 2023. https://www.monash.edu/medicine/sphpm/units/womenshealth/info-sheets/female-sexuality-changes-age (accessed March 6, 2023)

15.

D.R. Junqueira, D. Bennett, S.Y. Huh, C. Casañas i Comabella, Clinical Presentations of Drug-Induced Hyperprolactinaemia: A Literature Review. Pharm. Med. 37, 1–14 (2023)CrossRef

16.

D.L. Torre, A. Falorni, Pharmacological causes of hyperprolactinemia. Ther. Clin. Risk Manag. 3, 929–951 (2007)PubMedPubMedCentral

17.

M.E. Molitch, Medication-Induced Hyperprolactinemia. Mayo Clin. Proc. 80, 1050–1057 (2005). https://doi.org/10.4065/80.8.1050CrossRefPubMed

18.

S. Nazir, Z. Iqbal, L. Ahmad, S. Ahmad, Variation in pharmacokinetics of omeprazole and its metabolites by gender and CYP2C19 genotype in Pakistani male and female subjects. Pak. J. Pharm. Sci. 29, 887–894 (2016)PubMed

19.

A. Jabbar, R. Khan, S.N. Farrukh, Hyperprolactinaemia induced by proton pump inhibitor. JPMA J. Pak. Med. Assoc. 60, 689–690 (2010)PubMed

20.

N. Pipaliya, D. Solanke, C. Rathi, R. Patel, M. Ingle, P. Sawant, Esomeprazole induced galactorrhea: a novel side effect. Clin. J. Gastroenterol. 9, 13–16 (2016). https://doi.org/10.1007/s12328-015-0622-7CrossRefPubMed

21.

H. Rajgadhi, H. Makwana, S. Malhotra, P. Patel, Levosulpiride and Esomeprazole Induced Hyperprolactinemia Case Report of Drug Induced Hyperprolactinemia. Natl J. Integr. Res. Med. 8, 158–160 (2010)

22.

M. Prikis, J. MacDougall, N. Narasimhadevara, Proton Pump Inhibitor-Induced Galactorrhea in a Kidney Transplant Recipient: A Friend or Foe? Case Rep. Transpl. 2020, 8108730 (2020). https://doi.org/10.1155/2020/8108730CrossRef

23.

H.M. Conaglen, J.V. Conaglen, Drug-induced sexual dysfunction in men and women. Aust. Prescr. 36 (2013). https://doi.org/10.18773/austprescr.2013.021

24.

S.R. Davis, A.T. Guay, J.L. Shifren, N.A. Mazer, Endocrine aspects of female sexual dysfunction. J. Sex. Med. 1, 82–86 (2004). https://doi.org/10.1111/j.1743-6109.2004.10112.xCrossRefPubMed

25.

G.A. Maguire, Prolactin elevation with antipsychotic medications: mechanisms of action and clinical consequences. J. Clin. Psychiatry 63, 56–62 (2002)PubMed

26.

U. Halbreich, B.J. Kinon, J.A. Gilmore, L.S. Kahn, Elevated prolactin levels in patients with schizophrenia: mechanisms and related adverse effects. Psychoneuroendocrinology 28, 53–67 (2003). https://doi.org/10.1016/s0306-4530(02)00112-9CrossRefPubMed

27.

A. Majumdar, N.S. Mangal, Hyperprolactinemia. J. Hum. Reprod. Sci. 6, 168–175 (2013). https://doi.org/10.4103/0974-1208.121400CrossRefPubMedPubMedCentral

28.

L.T. Fourman, P.K. Fazeli, Neuroendocrine Causes of Amenorrhea—An Update. J. Clin. Endocrinol. Metab. 100, 812–824 (2015). https://doi.org/10.1210/jc.2014-3344CrossRefPubMedPubMedCentral

29.

S. Smith, M.J. Wheeler, R. Murray, V. O’Keane, The effects of antipsychotic-induced hyperprolactinaemia on the hypothalamic-pituitary-gonadal axis. J. Clin. Psychopharmacol. 22, 109–114 (2002). https://doi.org/10.1097/00004714-200204000-00002CrossRefPubMed

30.

H. Knegtering, R. van den Bosch, S. Castelein, R. Bruggeman, S. Sytema, J. van Os, Are sexual side effects of prolactin-raising antipsychotics reducible to serum prolactin? Psychoneuroendocrinology 33, 711–717 (2008). https://doi.org/10.1016/j.psyneuen.2008.02.008CrossRefPubMed

31.

T. Kishimoto, K. Watanabe, N. Shimada, K. Makita, G. Yagi, H. Kashima, Antipsychotic-induced hyperprolactinemia inhibits the hypothalamo-pituitary-gonadal axis and reduces bone mineral density in male patients with schizophrenia. J. Clin. Psychiatry 69, 385–391 (2008). https://doi.org/10.4088/jcp.v69n0307CrossRefPubMed

32.

A. Caufriez, Menstrual disorders associated with hyperprolactinemia. Horm. Res. 22, 209–214 (1985). https://doi.org/10.1159/000180096CrossRefPubMed

33.

D. Radojkovic, M. Pesic, M. Radojkovic, V. Ciric, S. Kostic, S. Curkovic et al., Menstrual disorders in patients with different etiology of hyperprolactinemia. Endocr Abstr. 63, P307 (2019). https://doi.org/10.1530/endoabs.63.P307

34.

M. Galea, Benign breast disorders. Surg. Oxf. 34, 19–24 (2016)

35.

E.B. Kilicdag, E. Tarim, T. Bagis, S. Erkanli, E. Aslan, K. Ozsahin et al. Fructus agni casti and bromocriptine for treatment of hyperprolactinemia and mastalgia. Int J. Gynaecol. Obstet. Organ Int Fed. Gynaecol. Obstet. 85, 292–293 (2004). https://doi.org/10.1016/j.ijgo.2004.01.001CrossRef

36.

B.M. Stringer, J. Rowson, E.D. Williams, Effect of raised serum prolactin on breast development. J. Anat. 162, 249–261 (1989)PubMedPubMedCentral

37.

M.E. Freeman, B. Kanyicska, A. Lerant, G. Nagy, Prolactin: structure, function, and regulation of secretion. Physiol. Rev. 80, 1523–1631 (2000). https://doi.org/10.1152/physrev.2000.80.4.1523CrossRefPubMed

38.

A.L. Torre, A. Conca, D. Duffy, G. Giupponi, M. Pompili, M. Grözinger, Sexual Dysfunction Related to Psychotropic Drugs: A Critical Review Part II: Antipsychotics. Pharmacopsychiatry 46, 201–208 (2013). https://doi.org/10.1055/s-0033-1347177CrossRefPubMed

39.

B.J. Kinon, J.A. Gilmore, H. Liu, U.M. Halbreich, Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials. Psychoneuroendocrinology 28, 69–82 (2003). https://doi.org/10.1016/S0306-4530(02)00128-2CrossRefPubMed

40.

A. Venkatanarasu, R. Boddula, S. Basavaraju, C. Chinte, V. Tickoo, Drug Induced Hyperprolactinemia. J. Endocr. Soc. 5, A626–A627 (2021). https://doi.org/10.1210/jendso/bvab048.1277CrossRefPubMedCentral

41.

S.R. Plymate, L.A. Matej, R.E. Jones, K.E. Friedl, Inhibition of Sex Hormone-Binding Globulin Production in the Human Hepatoma (Hep G2) Cell Line by Insulin and Prolactin*. J. Clin. Endocrinol. Metab. 67, 460–464 (1988). https://doi.org/10.1210/jcem-67-3-460CrossRefPubMed

42.

R.A. Lobo, O.A. Kletzky, Normalization of androgen and sex hormone-binding globulin levels after treatment of hyperprolactinemia. J. Clin. Endocrinol. Metab. 56, 562–566 (1983). https://doi.org/10.1210/jcem-56-3-562CrossRefPubMed

43.

H. Nagasawa, K. Miura, K. Niki, H. Namiki, Interrelationship between prolactin and progesterone in normal mammary gland growth in SHN virgin mice. Exp. Clin. Endocrinol. 86, 357–360 (1985). https://doi.org/10.1055/s-0029-1210509CrossRefPubMed

Titel: Effects of long-term proton pump inhibitor use on sexual hormones and sexual and reproductive health in female patients
verfasst von: Muhammad Ashfaq
Qasim Khan
Muhammad Zeeshan Haroon
Syed Mobasher Ali Abid
Muhammad Junaid Hassan Sharif
Yasser M. S. A. Alkahraman
Publikationsdatum: 01.11.2023
Verlag: Springer US
Erschienen in: Endocrine / Ausgabe 2/2024
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI: https://doi.org/10.1007/s12020-023-03572-8

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Effects of long-term proton pump inhibitor use on sexual hormones and sexual and reproductive health in female patients