Premature ovarian insufficiency: a syndrome or diagnosis

Т. Ф Татарчук, Н. В. Косей, Т. Н. Тутченко

Abstract


The article presents modern views on the etiology, pathogenesis, diagnosis and management of premature ovarian insufficiency (POI) – syndrome which is heterogeneous in the etiology and pathogenesis and has a significant negative impact not only on the reproductive sphere, but also on the quality of life, the overall morbidity and mortality of women.

The term “premature ovarian insufficiency” is used today by leading professional societies in the US and Europe and is recommended for use in clinical practice. In the clinical recommendations of 2016, the European Society for Human Reproductology and Embryology provides the following definition of the POI – the clinical syndrome whose main manifestation is the cessation of ovarian function before the age of 40, which is characterized by a disruption of menstrual function, an increase in gonadotropins and a decrease in the concentration of estradiol.

Given the already well-formed trend in developed countries for the late realization of reproductive function, a higher frequency of POI in a group of women of late reproductive age is an actual problem of modern reproductive technology.

The clinical significance of the POI goes beyond gynecology: prolonged hypoestrogenia is accompanied by a decrease in bone density, the disease also has negatively affects the incidence of cardiovascular and neurological diseases, cognitive function, sex life and the social realization of women.

Hormone replacement therapy is an obligatory and essential component of correction of symptoms and prevention of long-term consequences of estrogen deficiency. With this in mind, the article discusses in detail the effects and safety issues of the application of various types and ways of hormone replacement therapy available today for the elimination of symptoms of estrogen deficiency and the prevention of its consequences in women with POI and various concomitant conditions. The pharmacological effects of natural transdermal estrogens and micronized progesterone make it possible to treat this combination as the most optimal variant of hormone replacement therapy for women with POI due to the flexible dosage regimen that allows to provide individual needs for compensation of estrogen deficiency.


Keywords


premature ovarian insufficiency; estrogen deficiency; micronized progesterone; hormone replacement therapy

References


Albright, F., Smith, P., Fraser, R. “A syndrome characterized by primary ovarian insufficiency and decreased stature.” Am J Med Sci 204 (1942): 625–648.

Webber, L., et al. “ESHRE Guideline: management of women with premature ovarian insufficiency.” Human Reproduction 31.5 (2016): 926–37.

Pellegrini, V.A. “Ovarian Insufficiency.” Available from: [http://emedicine. medscape.com/article/271046-overview], last accessed Apr 12, 2017.

Popat, V.B., Calis, K.A., Kalantaridou, S.N., et al. “Bone mineral density in young women with primary ovarian insufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement.” J Clin Endocrinol Metab 99 (2014): 3418–26.

Shuster, L.T., et al. “Premature menopause or early menopause: long-term health consequences.” Maturitas 65.2 (2010): 161–6.

Knauff, E.A., Westerveld, H.E., Goverde, A.J., et al. “Lipid profile of women with premature ovarian failure.” Menopause 15 (2008): 919–23.

Eshtiaghi, R., Esteghamati, A., Nakhjavani, M. “Menopause is an independent predictor of metabolic syndrome in Iranian women.” Maturitas 65 (2010): 262–6.

Rocca, W.A., Grossardt, B.R., Miller, V.M., et al. “Premature menopause or early menopause and risk of ischaemic stroke.” Menopause 19 (2012): 272–7.

Rocca, W.A., Bower, J.H., Maraganore, D.M., et al. “Increased risk of parkinsonism in women who underwent oophorectomy before menopause.” Neurology 70 (2009): 200–9.

Soni, M., Hogervorst, E. “Premature ovarian insufficiency and neurological function.” Minerva Endocrinol 39 (2014): 189–99.

Wallace, W., Hamish, B., et al. “Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation.” The Lancet Oncology 15.10 (2014): 1129–36.

Anderson, R.A., et al. “Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults.” The Lancet Diabetes & endocrinology 3.7 (2015): 556–67.

Vujovic, S., et al. “Premature ovarian insufficiency: current point of view.” Maturitas 81.1 (2015): 108.

Maclaran, K., Panay, N. “Current concepts in premature ovarian insufficiency.” Women’s Health 11.2 (2015): 169–82.

Maclaran K, Panay N. Presentation and management of POF: findings from the West London POF database. Presented at: 15th World Congress of Gynecological Endocrinology. Florence, Italy, 7–10 March 2012.

Barnhart, K.T., Schreiber, C.A. “Return to fertility following discontinuation of oral contraceptives.” Fertility and Sterility 91.3 (2009): 659–63.

Hipp, H.S., et al. “Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI).” Menopause 23.9 (2016): 993–9.

Sherman, S.L. “Premature ovarian failure in the fragile X syndrome.” American journal of medical genetics 97.3 (2000): 189–94.

Silva, C.A., et al. “Autoimmune primary ovarian insufficiency.” Autoimmunity reviews 13.4 (2014): 427–30.

Dewailly, D., et al. “The physiology and clinical utility of anti-Müllerian hormone in women.” Human reproduction update 20.3 (2014): 370–85.

Pellegrini, V.A. “Ovarian Insufficiency.” Available from: [http://emedicine. medscape.com/article/271046-overview#a5], last accessed Apr 12, 2017.

Bentzen, J.G., et al. “Maternal menopause as a predictor of anti-Müllerian hormone level and antral follicle count in daughters during reproductive age.” Human reproduction (2012): des356.

Piccioni, P., Scirpa, P., D’Emilio, I., et al. “Hormonal replacement therapy after stem cell transplantation.” Maturitas 49 (2004): 327–33.

Madalinska, J.B., van Beurden, M., Bleiker, E.M., et al. “The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy.” J Clin Oncol 24 (2006): 3576–82.

Absolom, K., Eiser, C., Turner, L., et al. “Ovarian failure following cancer treatment: current management and quality of life.” Hum Reprod 23 (2008): 2506–12.

Kalantaridou, S.N., Naka, K.K., Papanikolaou, E., et al. “Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy.” J Clin Endocrinol Metab 89 (2004): 3907–13.

Lokkegaard, E., Jovanovic, Z., Heitmann, B.L., et al. “The association between early menopause and risk of ischaemic heart disease: influence of Hormone Therapy.” Maturitas 53 (2006): 226–33.

Ostberg, J.E., Storry, C., Donald, A.E., et al. “A dose-response study of hormone replacement in young hypogonadal women: effects on intima media thickness and metabolism.” Clin Endocrinol 66 (2007): 557–64.

Langrish, J.P., Mills, N.L., Bath, L.E., et al. “Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure.” Hypertension 53 (2009): 805–11.

Kanis, J.A., McCloskey, E.V., Johansson, H., et al. “Scientific Advisory Board of the European Society for C, Economic Aspects of O, Osteoarthritis, the Committee of Scientific Advisors of the International Osteoporosis F. European guidance for the diagnosis and management of osteoporosis in postmenopausal women.” Osteoporos Int 24 (2013): 23–57.

Benetti-Pinto, C.L., Soares, P.M., Magna, L.A., et al. “Breast density in women with premature ovarian failure using hormone therapy.” Gynecol Endocrinol 24 (2008): 40–3.

Soares, P.M., Cabello, C., Magna, L.A., et al. “Breast density in women with premature ovarian failure or postmenopausal women using hormone therapy: analytical cross-sectional study.” Sao Paulo Med J 128 (2010): 211–4.

Wu, X., Cai, H., Kallianpur, A., et al. “Impact of Premature Ovarian Failure on Mortality and Morbidity among ChineseWomen.” PloS One 9 (2014):e89597.

Crofton, P.M., Evans, N., Bath, L.E., et al. “Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover.” Clin Endocrinol 73 (2010): 707–14.

Popat, V.B., Vanderhoof, V.H., Calis, K.A., et al. “Normalization of serum luteinizing hormone levels in women with 46, XX spontaneous primary ovarian insufficiency.” Fertil Steril 89 (2008): 429–33.

Bitran, D., Shiekh, M., McLeod, M. “Anxiolytic effect of progesterone is mediated by the neurosteroid allopregnanolone at brain GABAA receptors.” Journal of neuroendocrinology 7.3 (1995): 171–7.

Nappi, R.E., Cagnacci, A., Granella, F., et al. “Course of primary headaches during hormone replacement therapy.” Maturitas 38 (2001): 157–63.

White, W.B. “Drospirenone with 17beta-estradiol in the postmenopausal woman with hypertension.” Climacteric 10 Suppl 1 (2007): 25–31.

Canonico, M., Plu-Bureau, G., Lowe, G.D., Scarabin, P.Y. “Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis.” Br Med J 336 (2008): 1227–31.

Canonico, M., Oger, E., Conard, J., et al. “Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration. The ESTHER Study.” J Thromb Haemost 4 (2006): 1259–65.

Nelson, L.M., Covington, S.N., Rebar, R.W. “An update: spontaneous premature ovarian failure is not an early menopause.” Fertil Steril 83 (2005): 1327–32.

Castaneda, S., Carmona, L., Carvajal, I., et al. “Reduction of bone mass in women after bone marrow transplantation.” Calcif Tissue Int 60 (1997): 343–7.

Bakalov, V.K., Axelrod, L., Baron, J., et al. “Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency.” J Clin Endocrinol Metab 88 (2003): 5717–22.

Han, T.S., Goswami, D., Trikudanathan, S., et al. “Comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis.” Eur J Endocrinol 159 (2008): 179–85.

Bachelot, A., Rouxel, A., Massin, N., et al. “Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure.” Eur J Endocrinol 161 (2009): 179–87.

Freriks, K., Timmermans, J., Beerendonk, C.C., et al. “Standardized multidisciplinary evaluation yields significant previously undiagnosed morbidity in adult women with Turner syndrome.” J Clin Endocrinol Metab 96 (2011): E1517–26.

Bours, S.P., van Geel, T.A., Geusens, P.P., et al. “Contributors to secondary osteoporosis and metabolic bone diseases in patients presenting with a clinical fracture.” J Clin Endocrinol Metab 96 (2011): 1360–7.

Challoumas, D., Cobbold, C., Dimitrakakis, G. “Effects of calcium intake on the cardiovascular system in postmenopausal women.” Atherosclerosis 231 (2013): 1–7.

Cartwright, B., et al. “Hormone Replacement Therapy Versus the Combined Oral Contraceptive Pill in Premature Ovarian Failure: A Randomized Controlled Trial of the Effects on Bone Mineral Density.” The Journal of Clinical Endocrinology & Metabolism 101.9 (2016): 3497–505.

Muka, T., Oliver-Williams, C., Kunutsor, S., et al. “Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: a systematic review and meta-analysis.” JAMA Cardiol (2016).

Roeters van Lennep, J.E., et al. “Cardiovascular disease risk in women with premature ovarian insufficiency: A systematic review and meta-analysis.” European journal of preventive cardiology 23.2 (2016): 178–86.

Pacello, P.C., Yela, D.A., Rabelo, S., et al. “Dyspareunia and lubrication in premature ovarian failure using hormonal therapy and vaginal health.” Climacteric 17 (2014): 342–7.


GOST Style Citations


1. Albright, F., Smith, P., Fraser, R. “A syndrome characterized by primary ovarian insufficiency and decreased stature.” Am J Med Sci 204 (1942): 625–648.

2. Webber, L., et al. “ESHRE Guideline: management of women with premature ovarian insufficiency.” Human Reproduction 31.5 (2016): 926–37.

3. Pellegrini, V.A. “Ovarian Insufficiency.” Available from: [http://emedicine. medscape.com/article/271046-overview], last accessed Apr 12, 2017.

4. Popat, V.B., Calis, K.A., Kalantaridou, S.N., et al. “Bone mineral density in young women with primary ovarian insufficiency: results of a three-year randomized controlled trial of physiological transdermal estradiol and testosterone replacement.” J Clin Endocrinol Metab 99 (2014): 3418–26.

5. Shuster, L.T., et al. “Premature menopause or early menopause: long-term health consequences.” Maturitas 65.2 (2010): 161–6.

6. Knauff, E.A., Westerveld, H.E., Goverde, A.J., et al. “Lipid profile of women with premature ovarian failure.” Menopause 15 (2008): 919–23.

7. Eshtiaghi, R., Esteghamati, A., Nakhjavani, M. “Menopause is an independent predictor of metabolic syndrome in Iranian women.” Maturitas 65 (2010): 262–6.

8. Rocca, W.A., Grossardt, B.R., Miller, V.M., et al. “Premature menopause or early menopause and risk of ischaemic stroke.” Menopause 19 (2012): 272–7.

9. Rocca, W.A., Bower, J.H., Maraganore, D.M., et al. “Increased risk of parkinsonism in women who underwent oophorectomy before menopause.” Neurology 70 (2009): 200–9.

10. Soni, M., Hogervorst, E. “Premature ovarian insufficiency and neurological function.” Minerva Endocrinol 39 (2014): 189–99.

11. Wallace, W., Hamish, B., et al. “Fertility preservation for girls and young women with cancer: population-based validation of criteria for ovarian tissue cryopreservation.” The Lancet Oncology 15.10 (2014): 1129–36.

12. Anderson, R.A., et al. “Cancer treatment and gonadal function: experimental and established strategies for fertility preservation in children and young adults.” The Lancet Diabetes & endocrinology 3.7 (2015): 556–67.

13. Vujovic, S., et al. “Premature ovarian insufficiency: current point of view.” Maturitas 81.1 (2015): 108.

14. Maclaran, K., Panay, N. “Current concepts in premature ovarian insufficiency.” Women’s Health 11.2 (2015): 169–82.

15. Maclaran K, Panay N. Presentation and management of POF: findings from the West London POF database. Presented at: 15th World Congress of Gynecological Endocrinology. Florence, Italy, 7–10 March 2012.

16. Barnhart, K.T., Schreiber, C.A. “Return to fertility following discontinuation of oral contraceptives.” Fertility and Sterility 91.3 (2009): 659–63.

17. Hipp, H.S., et al. “Reproductive and gynecologic care of women with fragile X primary ovarian insufficiency (FXPOI).” Menopause 23.9 (2016): 993–9.

18. Sherman, S.L. “Premature ovarian failure in the fragile X syndrome.” American journal of medical genetics 97.3 (2000): 189–94.

19. Silva, C.A., et al. “Autoimmune primary ovarian insufficiency.” Autoimmunity reviews 13.4 (2014): 427–30.

20. Dewailly, D., et al. “The physiology and clinical utility of anti-Müllerian hormone in women.” Human reproduction update 20.3 (2014): 370–85.

21. Pellegrini, V.A. “Ovarian Insufficiency.” Available from: [http://emedicine. medscape.com/article/271046-overview#a5], last accessed Apr 12, 2017.

22. Bentzen, J.G., et al. “Maternal menopause as a predictor of anti-Müllerian hormone level and antral follicle count in daughters during reproductive age.” Human reproduction (2012): des356.

23. Piccioni, P., Scirpa, P., D’Emilio, I., et al. “Hormonal replacement therapy after stem cell transplantation.” Maturitas 49 (2004): 327–33.

24. Madalinska, J.B., van Beurden, M., Bleiker, E.M., et al. “The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy.” J Clin Oncol 24 (2006): 3576–82.

25. Absolom, K., Eiser, C., Turner, L., et al. “Ovarian failure following cancer treatment: current management and quality of life.” Hum Reprod 23 (2008): 2506–12.

26. Kalantaridou, S.N., Naka, K.K., Papanikolaou, E., et al. “Impaired endothelial function in young women with premature ovarian failure: normalization with hormone therapy.” J Clin Endocrinol Metab 89 (2004): 3907–13.

27. Lokkegaard, E., Jovanovic, Z., Heitmann, B.L., et al. “The association between early menopause and risk of ischaemic heart disease: influence of Hormone Therapy.” Maturitas 53 (2006): 226–33.

28. Ostberg, J.E., Storry, C., Donald, A.E., et al. “A dose-response study of hormone replacement in young hypogonadal women: effects on intima media thickness and metabolism.” Clin Endocrinol 66 (2007): 557–64.

29. Langrish, J.P., Mills, N.L., Bath, L.E., et al. “Cardiovascular effects of physiological and standard sex steroid replacement regimens in premature ovarian failure.” Hypertension 53 (2009): 805–11.

30. Kanis, J.A., McCloskey, E.V., Johansson, H., et al. “Scientific Advisory Board of the European Society for C, Economic Aspects of O, Osteoarthritis, the Committee of Scientific Advisors of the International Osteoporosis F. European guidance for the diagnosis and management of osteoporosis in postmenopausal women.” Osteoporos Int 24 (2013): 23–57.

31. Benetti-Pinto, C.L., Soares, P.M., Magna, L.A., et al. “Breast density in women with premature ovarian failure using hormone therapy.” Gynecol Endocrinol 24 (2008): 40–3.

32. Soares, P.M., Cabello, C., Magna, L.A., et al. “Breast density in women with premature ovarian failure or postmenopausal women using hormone therapy: analytical cross-sectional study.” Sao Paulo Med J 128 (2010): 211–4.

33. Wu, X., Cai, H., Kallianpur, A., et al. “Impact of Premature Ovarian Failure on Mortality and Morbidity among ChineseWomen.” PloS One 9 (2014):e89597.

34. Crofton, P.M., Evans, N., Bath, L.E., et al. “Physiological versus standard sex steroid replacement in young women with premature ovarian failure: effects on bone mass acquisition and turnover.” Clin Endocrinol 73 (2010): 707–14.

35. Popat, V.B., Vanderhoof, V.H., Calis, K.A., et al. “Normalization of serum luteinizing hormone levels in women with 46, XX spontaneous primary ovarian insufficiency.” Fertil Steril 89 (2008): 429–33.

36. Bitran, D., Shiekh, M., McLeod, M. “Anxiolytic effect of progesterone is mediated by the neurosteroid allopregnanolone at brain GABAA receptors.” Journal of neuroendocrinology 7.3 (1995): 171–7.

37. Nappi, R.E., Cagnacci, A., Granella, F., et al. “Course of primary headaches during hormone replacement therapy.” Maturitas 38 (2001): 157–63.

38. White, W.B. “Drospirenone with 17beta-estradiol in the postmenopausal woman with hypertension.” Climacteric 10 Suppl 1 (2007): 25–31.

39. Canonico, M., Plu-Bureau, G., Lowe, G.D., Scarabin, P.Y. “Hormone replacement therapy and risk of venous thromboembolism in postmenopausal women: systematic review and meta-analysis.” Br Med J 336 (2008): 1227–31.

40. Canonico, M., Oger, E., Conard, J., et al. “Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration. The ESTHER Study.” J Thromb Haemost 4 (2006): 1259–65.

41. Nelson, L.M., Covington, S.N., Rebar, R.W. “An update: spontaneous premature ovarian failure is not an early menopause.” Fertil Steril 83 (2005): 1327–32.

42. Castaneda, S., Carmona, L., Carvajal, I., et al. “Reduction of bone mass in women after bone marrow transplantation.” Calcif Tissue Int 60 (1997): 343–7.

43. Bakalov, V.K., Axelrod, L., Baron, J., et al. “Selective reduction in cortical bone mineral density in turner syndrome independent of ovarian hormone deficiency.” J Clin Endocrinol Metab 88 (2003): 5717–22.

44. Han, T.S., Goswami, D., Trikudanathan, S., et al. “Comparison of bone mineral density and body proportions between women with complete androgen insensitivity syndrome and women with gonadal dysgenesis.” Eur J Endocrinol 159 (2008): 179–85.

45. Bachelot, A., Rouxel, A., Massin, N., et al. “Phenotyping and genetic studies of 357 consecutive patients presenting with premature ovarian failure.” Eur J Endocrinol 161 (2009): 179–87.

46. Freriks, K., Timmermans, J., Beerendonk, C.C., et al. “Standardized multidisciplinary evaluation yields significant previously undiagnosed morbidity in adult women with Turner syndrome.” J Clin Endocrinol Metab 96 (2011): E1517–26.

47. Bours, S.P., van Geel, T.A., Geusens, P.P., et al. “Contributors to secondary osteoporosis and metabolic bone diseases in patients presenting with a clinical fracture.” J Clin Endocrinol Metab 96 (2011): 1360–7.

48. Challoumas, D., Cobbold, C., Dimitrakakis, G. “Effects of calcium intake on the cardiovascular system in postmenopausal women.” Atherosclerosis 231 (2013): 1–7.

49. Cartwright, B., et al. “Hormone Replacement Therapy Versus the Combined Oral Contraceptive Pill in Premature Ovarian Failure: A Randomized Controlled Trial of the Effects on Bone Mineral Density.” The Journal of Clinical Endocrinology & Metabolism 101.9 (2016): 3497–505.

50. Muka, T., Oliver-Williams, C., Kunutsor, S., et al. “Association of age at onset of menopause and time since onset of menopause with cardiovascular outcomes, intermediate vascular traits, and all-cause mortality: a systematic review and meta-analysis.” JAMA Cardiol (2016).

51. Roeters van Lennep, J.E., et al. “Cardiovascular disease risk in women with premature ovarian insufficiency: A systematic review and meta-analysis.” European journal of preventive cardiology 23.2 (2016): 178–86.

52. Pacello, P.C., Yela, D.A., Rabelo, S., et al. “Dyspareunia and lubrication in premature ovarian failure using hormonal therapy and vaginal health.” Climacteric 17 (2014): 342–7.





DOI: http://dx.doi.org/10.18370/2309-4117.2017.34.16-22

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