The prevalence and phenotypic characteristics of spontaneous premature ovarian failure: a general population registry-based study

Hum Reprod. 2015 May;30(5):1229-38. doi: 10.1093/humrep/dev021. Epub 2015 Feb 23.


Study question: What is the measured prevalence and phenotype of spontaneous premature ovarian failure (POF) in the general population?

Summary answer: Spontaneous POF occurs in ∼1% of the general population with unique phenotype of post-menopausal ageing distinct from surgically induced premature menopause.

What is known already: POF is multifactorial ovarian quiescence before the age of 40. The clinical features of POF are diverse and the population prevalence of POF is still not known.

Study design, size, duration: This population-depictive registry-based case-cohort study included 34 041 women from the Estonian Genome Center registered between 2003 and 2013.

Participants/materials, setting, methods: Spontaneous POF was selected retrospectively by excluding other causes for premature menopause under the age of 40 (N = 310) and women with surgically induced premature menopause participated as a reference group (N = 242).

Main results and the role of chance: The prevalence of spontaneous POF was 0.91% (0.81-1.02%) among women of the general population in Estonia. In women with POF, menarche occurred a few months later than in the reference group and a significantly higher number of live births during their reproductive life was recorded. Women with POF also consumed less alcohol and had smaller waist-to-hip ratios than those in the reference group, although both groups of women were similar in body mass index a decade after menopause. The prevalence of concomitant diseases was similar between two groups of women by their fifties, but the pattern of onset of these diseases was different. Surgically induced premature menopause associated with faster development of osteoporosis, hypertension, and connective tissue diseases, but slower development of allergies, compared with spontaneous POF. The age of menopause was determined by irregular menstrual cycles, but not by the length of regular menstrual cycles, the age of menarche, the number of pregnancies or live births, smoking or alcohol consumption, or the use of oral contraceptives for some time during the reproductive period.

Limitations, reasons for caution: POF is rarely stated in medical records and cannot be diagnosed retrospectively by standard procedures. Therefore the data on all cases of women with primary amenorrhea or premature menopause before the age of 40 were requested from the registry and spontaneous POF was predicted retrospectively by excluding other extraovarian causes for premature menopause. Since the current study is retrospective registry-based data analysis, no genetic evaluation concerning possible candidate genes and no blood analysis concerning immunologic disorders could be performed to describe etiopathogenesis of POF.

Wider implication of the findings: Spontaneous POF most likely comprises several diseases with different etiopathologies and there may be a unique phenotype of post-menopausal ageing distinct from that in surgically induced premature menopause. Irregular menstrual cycles may be a prospective risk for developing spontaneous POF. Compared with spontaneous POF, surgically induced premature menopause associates with faster development of age-related diseases. The data point to new ideas and hypotheses for further studies on etiopathologies and treatment options for spontaneous POF.

Study funding/competing interests: The study was funded by grant SF0180044s09, SF0180027s10 and IUT20-43 from the Estonian Ministry of Education and Research, Enterprise Estonia, grant no EU30020, Eureka's EUROSTARS programme grant (NOTED, EU41564). No competing interests are declared.

Keywords: concomitant diseases; fecundity; phenotype; population prevalence; premature ovarian failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Cohort Studies
  • Estonia
  • Female
  • Humans
  • Menopause, Premature
  • Middle Aged
  • Phenotype
  • Prevalence
  • Primary Ovarian Insufficiency / diagnosis*
  • Primary Ovarian Insufficiency / epidemiology*
  • Registries
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors