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Year : 2021  |  Volume : 14  |  Issue : 6  |  Page : 674-678  

Etiology of primary amenorrhea: Experience from a tertiary care hospital in Western India

1 Department of Obstetrics and Gynaecology, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Obstetrics & Gynaecology, Command Hospital (AF), Bengaluru, Karnataka, India

Date of Submission28-Jul-2020
Date of Decision02-Oct-2020
Date of Acceptance09-Dec-2020
Date of Web Publication12-Feb-2021

Correspondence Address:
Rajesh Kumar Mishra
Department of Obstetrics and Gynaecology, Armed Forces Medical College, Golden Jubilee Block, Solapur Road, Pune - 411 040, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mjdrdypu.mjdrdypu_395_20

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Objectives: The etiology of primary amenorrhea is varied and can involve different organ systems. Gonadal dysgenesis and Mullerian agenesis are two most common disorders contributing to it. However, there is no consensus about the prevalence of different etiologies among studies reported from different parts of the world. The present study was carried out to evaluate different etiological factors responsible for primary amenorrhea in Western India. Materials and Methods: This was a prospective observational study carried out at a tertiary care hospital in Maharashtra. Thirty cases of primary amenorrhea were evaluated over a period of 2 years and data were analyzed regarding etiology and various management options. Results: Fourteen out of 30 cases had Mullerian agenesis and gonadal dysgenesis was reported in five cases. No case of genital tuberculosis was reported in our study. Most cases of Mullerian agenesis were managed with vaginoplasty, whereas cases of gonadal dysgenesis were managed with cyclical hormonal therapy. Conclusion: Mullerian agenesis was the most common etiology of primary amenorrhea followed by gonadal dysgenesis in our study. Diagnosis of patients of amenorrhea should be meticulous and their management depends on the underlying etiology.

Keywords: Amenorrhea, gonadal dysgenesis, Mayer-Rokitansky-Kuster-Hauser syndrome, Mullerian agenesis

How to cite this article:
Mishra RK, Kohli UA, Seth A, Tripathy SR. Etiology of primary amenorrhea: Experience from a tertiary care hospital in Western India. Med J DY Patil Vidyapeeth 2021;14:674-8

How to cite this URL:
Mishra RK, Kohli UA, Seth A, Tripathy SR. Etiology of primary amenorrhea: Experience from a tertiary care hospital in Western India. Med J DY Patil Vidyapeeth [serial online] 2021 [cited 2021 Dec 6];14:674-8. Available from: https://www.mjdrdypv.org/text.asp?2021/14/6/674/309189

  Introduction Top

Menstruation is the physiological cyclical shedding of blood and the endometrial lining of the uterus. Menarche; which refers to the initiation of menstruation is the last event of all pubertal changes and marks the onset of reproductive life in a girl. Menstruation requires a well-coordinated hypothalamic pituitary ovarian axis, an endometrium responsive to the ovarian hormones, and a patent outflow tract. Abnormality in any one of the above pathways leads to amenorrhea.[1] According to an estimate of the World Health Organization, amenorrhea is the sixth-largest contributor of female infertility accounting for almost 15% of total cases. It can affect 2%–5% of all women in reproductive age.[2] Amenorrhea is defined as the absence of menstruation in women of reproductive age. It is a symptom rather than a disease and the cause can be either physiological or pathological. The diagnosis of no other problem in gynecologic endocrinology is as challenging as that of amenorrhea. The diagnosis requires considering a number of varied and complex diseases and disorders which include different organ systems. Some of the disorders causing amenorrhea may have serious consequences, if not diagnosed and treated effectively. Hence, a systematic and logical approach is required when dealing with such patients.

Conventionally, amenorrhea has been classified as primary or secondary. Primary amenorrhea refers to failure of onset of menses by 14 years of age in the absence of development of secondary sexual characteristics or by 16 years of age regardless of the development of secondary sexual characteristics. On the other hand, secondary amenorrhea refers to failure of occurrence of menses for 6 months or an interval equivalent to a total of at least three previous cycles in women who have menstruated previously.[1]

The prevalence of primary amenorrhea is <1% in the United States and does not appear to differ with ethnicity.[3] The incidence seems to be increasing gradually with increased awareness and better utilization of health services.[4] Many studies have been published in literature from different parts of the globe on etiological factors associated with primary amenorrhea. The two important causes reported are Mullerian anomalies and gonadal dysgenesis which vary in frequencies in different parts. The Indian studies on this subject also vary in opinion regarding the frequency of different etiologies. Some have reported Mullerian anomalies to be commoner than gonadal dysgenesis while others have reported otherwise. Therefore, we conducted a study to determine the incidence of etiologic factors responsible for primary amenorrhea in Western India.

  Materials and Methods Top

A prospective observational study was carried out at a tertiary care hospital in Maharashtra over a period of 2 years from January 2017 to December 2018. All patients presenting to gynecology clinics with a history of primary amenorrhea were included in the study. Each patient was evaluated and suitable investigations were done to reach the final diagnosis. The evaluation included the following:


Data were collected about the age of patient at presentation, associated complaints with amenorrhea such as cyclical pain or urinary complaints. History was taken about their eating habits and exercise pattern, symptoms of galactorrhea, androgen excess, or thyroid abnormality. Any changes in weight, medication use, especially hormonal supplements or drugs that can affect central neurotransmitter release, any history of chronic systemic illness or tuberculosis were noted. Specific history for Central Nervous System disorder and estrogen deficiency was elicited. Family history of amenorrhea, mental retardation was also recorded.

Physical examination

Height, weight, and body mass index (BMI) were recorded. The skin was inspected to rule out peripheral stigmata of Turner syndrome, thyroid disorder, insulin resistance, and features of hyperandrogenism. The presence of secondary sexual characters and Tanner staging of breast and pubic hair were also noted. Local examination of the inguinal region and external genitalia was carried out. Per vaginal and per rectal examination were done to assess the genital outflow tract and uterus if required.


First, the urine pregnancy test was done to rule out pregnancy. Hormonal profiles of patients were done which included serum follicle-stimulating hormone, luteinizing hormone, prolactin, and thyroid-stimulating hormone levels. Additional hormonal and enzyme assay were done in selected cases when required. Ultrasonographic evaluation of both abdomen and pelvis was done to evaluate the uterus, adnexa, gonadal structures, or anomalies of reproductive and urinary tracts. Magnetic resonance imaging (MRI) was done to confirm the diagnosis in case the ultrasonography was not conclusive. Hysteroscopy or laparoscopy was done in selected cases for diagnosis and management. Karyotyping of patients was done to reach at the final diagnosis when required.

The patients were categorized into the following four groups depending on the etiology of primary amenorrhea which was based on the organs involved:

  • Category 1: Disorders of genital outflow tract and uterus
  • Category 2: Disorders of the ovary
  • Category 3: Disorders of the anterior pituitary
  • Category 4: Disorders of the hypothalamus.

A total of 32 patients who presented with primary amenorrhea were included in the study. A written informed consent was taken from the patients before including them in the study. Ethical clearance was taken from the Institutional Ethical Committee before onset of study. (Letter No: IEC November 2016 date 2016 November, 15).

  Results Top

Two out of 32 patients had constitutional delay of menarche and thus were excluded from the final analysis of results.

The presenting age of patients included in our study ranged from 13 to 26 years. The age distribution of the study group is depicted in [Graph 1].

The patients of primary amenorrhea in our study presented with varied complaints to the gynecologist most common being amenorrhea. The distribution of presenting complaints is tabulated in [Table 1].
Table 1: Distribution of presenting complaints

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In our study, Mullerian agenesis was the most common cause of primary amenorrhea contributing to 46.7% of cases (n = 14). The other causes of primary amenorrhea included imperforate hymen (three cases), transverse vaginal septum, androgen insensitivity syndrome, and endometrial dysfunction. Karyotyping was done for all patients with gonadal dysgenesis (five cases, 16.7%) which included two cases of Swyer syndrome (46, XY), one case of Turner syndrome and two had 46, XX gonadal dysgenesis. Two cases each were attributed to disorders of the pituitary and hypothalamus. The distribution of study population as per etiology is illustrated in [Table 2] and [Figure 1].
Table 2: Distribution of etiology

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Figure 1: Etiology of Primary Amenorrhea

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The management of cases of primary amenorrhea depends on the underlying etiology. Of 14 cases of Mullerian agenesis, six cases underwent Mc Indoe's vaginoplasty, two cases underwent serial vaginal dilatation with prosthetic dilators while others have been counseled about other available treatment options as they were unwilling for surgical management at present.

Imperforate hymen was treated with incision and drainage. Transverse vaginal septum was excised in the single reported case.

Patients diagnosed to have primary gonadal failure were treated with combined hormonal therapy with estrogen (conjugated equine estrogen 0.625 mg daily) for 21 days and progesterone (medroxyprogesterone acetate 10 mg daily) in the last 10 days of the cycle.

Cases of Swyer syndrome and AIS (Androgen insensitivity syndrome) were managed with gonadectomy to prevent the development of gonadoblastoma. Patients with disorders of the pituitary and hypothalamus were treated on case to case basis.

  Discussion Top

Primary amenorrhea is a cause for concern mostly in teenage girls with impact on physical, psychological, and social life of the patient. The management of such cases should focus both on medical and psychosocial aspects. Most of the patients in our study were <20 years of age and four patients were married. The most common presenting complaint was amenorrhea. Patients below 15 years were mainly the cases of imperforate hymen who present to doctors with complaints of cyclical pain abdomen or retention of urine rather than amenorrhea. There were two cases in our study who were evaluated only when they sought treatment for infertility.

The most common cause of primary amenorrhea in our study was Mullerian agenesis contributing to almost half of the cases (46.7%). This finding is in accordance to other Indian studies cited in literature. A study conducted by Kriplani et al. found the incidence of Mullerian anomaly among cases of primary amenorrhea to be 47% (48 out of 102 cases) in the North Indian population.[4] A study from Gujarat reported incidence of 44%[5] and Kumar and Mittal reported incidence of 54.2%.[6] A study from Thailand also reported Mullerian anomaly as the most common cause.[7]

However, this finding was in contrast to several studies cited in Western literature. Gonadal dysgenesis is found to be the most common cause in studies conducted in the USA.[8] A study conducted in Turkey had revealed a high incidence of chromosomal anomalies in cases of primary amenorrhea or primary ovarian insufficiency.[9] Some Indian studies have also reported gonadal dysgenesis to be the most common etiology.[10],[11] It is evident from above that there is a lot of variation in the prevalence of different disorders which can be attributed to the difference in environmental and racial or genetic factors.

The incidence of genital tuberculosis in cases of primary amenorrhea in the Indian population is reported to be 6.3%–7.8%.[4],[5] Although many Indian studies have depicted genital tuberculosis as one of the important causes of primary amenorrhea, our study did not find any case of genital tuberculosis as an etiology of primary amenorrhea. We are of the opinion that although genital TB is a common cause of secondary amenorrhea, it may not be as common a cause for primary amenorrhea.

In our study, a single case of endometrial dysfunction was reported in which no abnormality was detected either in the hormonal profile or imaging procedures. Cytogenetic evaluation revealed the karyotype of the patient as 46, XX. After a failure of hormonal therapy, she was further evaluated by hysteroscopy and endometrial biopsy which showed absent endometrium.

Two cases of primary amenorrhea were attributed to the pituitary in our study. One of the cases had hypopituitarism diagnosed by MRI which showed hypoplasia of anterior pituitary lobe. She was managed with combined hormonal therapy (Estrogen + Progesterone) in addition to supplements of eltroxin and hydrocortisone. The other case had hyperprolactinemia due to pituitary macroadenoma which was managed surgically.

Similarly, two cases were attributed to pathology at the level of the hypothalamus. One of the cases had idiopathic hypogonadotropic hypogonadism which was managed with exogenous GnRH analogs. The other case was diagnosed as nonclassic congenital adrenal hyperplasia due to a deficiency of enzyme 21-hydroxylase. She was managed with combined hormonal therapy in addition to glucocorticoid supplements.

The management of cases of primary amenorrhea requires multidisciplinary approach involving gynecologist, pediatrician, geneticist, and psychologist. The management protocol for each patient should be individualized and proper counseling should be done. The primary goal in cases of Mullerian agenesis is creation of a functional vagina which can be achieved by variety of methods. Nonsurgical method includes progressive vaginal dilatation using serial vaginal dilators (Franks/Ingrams). Surgical procedures aim to create a neovagina by dissection between the bladder anteriorly and the rectum posteriorly. Most cases of Mayer–Rokitansky–Kuster–Hauser syndrome (MRKH) and Mullerian agenesis were managed with Mc Indoe's vaginoplasty in our center with success. Other surgical procedures include Vecchietti operation, Davydov vaginoplasty, and William's vaginoplasty. They were also counseled about the possibility of surrogacy, adoption, and uterine transplant as other options for fertility. These patients were also offered in vitro fertilization procedures for fertility. Vaginoplasty still remains a preferred modality of the treatment for Mullerian agenesis in the Indian population as has been reported in other Indian studies.[4]

The present study is a prospective study and depicts the etiology and management of cases of primary amenorrhea at a tertiary care hospital in Maharashtra. The most significant limitation of our study was the limited sample size. Another limitation was that being a single center study, the study population might have been affected by the pattern of referral from other centers.

  Conclusion Top

The present study has demonstrated that Mullerian anomaly is the most common etiology of primary amenorrhea followed by gonadal dysgenesis. An important finding of our study was that genital tuberculosis is a rare case of primary amenorrhea. The frequency of different etiologies of primary amenorrhea in our study differs from some other Indian studies. The key to correct diagnosis of primary amenorrhea is sound theoretical knowledge and a multidisciplinary approach. The workup of such patients requires a mathematical approach including meticulous clinical examination, laboratory investigations, and imaging. The future reproductive and psychosocial lives of such patients depend on the early recognition of the primary etiology of amenorrhea and timely intervention.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Fritz M. and Speroff L. 2011. Clinical Gynecologic Endocrinology And Infertility. 8th ed. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins, p.435-93.  Back to cited text no. 1
Diczfalusy E. WHO Special Programme of Research, Development, and Research Training in Human Reproduction. The first fifteen years: A review. Contraception 1986;34:1-19.  Back to cited text no. 2
Hoffman B. and Williams J. 2016. Williams Gynecology. 3rd ed. New York: McGraw-Hill Medical, pp.369-385.  Back to cited text no. 3
Kriplani A, Goyal M, Kachhawa G, Mahey R, Kulshrestha V. Etiology and management of primary amenorrhoea: A study of 102 cases at tertiary centre. Taiwan J Obstet Gynecol 2017;56:761-4.  Back to cited text no. 4
Shah TM, Lalcheta FR. Case series of primary amenorrhea. Int J Curr Res 2018;10:70666-9.  Back to cited text no. 5
Kumar A, Mittal S. Primary amenorrhoea: Analysis of 48 cases. J Indian Med Assoc 1998;96:119-20.  Back to cited text no. 6
Tanmahasamut P, Rattanachaiyanont M, Dangrat C, Indhavivadhana S, Angsuwattana S, Techatraisak K. Causes of primary amenorrhea: A report of 295 cases in Thailand. J Obstet Gynaecol Res 2012;38:297-301.  Back to cited text no. 7
Reindollar RH, Byrd JR, McDonough PG. Delayed sexual development: A study of 252 patients. Am J Obstet Gynecol 1981;140:371-80.  Back to cited text no. 8
Geckinli BB, Toksoy G, Sayar C, Soylemez MA, Yesil G, Aydın H, et al. Prevalence of X-aneuploidies, X-structural abnormalities and 46, XY sex reversal in Turkish women with primary amenorrhea or premature ovarian insufficiency. Eur J Obstet Gynecol Reprod Biol 2014;182:211-5.  Back to cited text no. 9
Kallepalli P, Kallepalli D. A study of primary amenorrhea cases in north coastal Andhra Pradesh. IOSR J Dent Med Sci 2019;4:47-50.  Back to cited text no. 10
Hassan Z, Abbas R, Abbas F, Gayas M. Etiological profile of primary amenorrhea in Kashmir valley. Glob J Res Anal 2019;8:199-201.  Back to cited text no. 11


  [Figure 1]

  [Table 1], [Table 2]


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