The body manufactures three main kinds of estrogen: estradiol, estrone, and estriol. Estrogens are promoters of tissue growth, stimulating the proliferation of cells in the reproductive organs of women, particularly in the endometrium, the blood-rich lining of the uterus that is shed during menstruation. The collective effect of estrogen (the “estrogen effect”) in a woman’s body can be estimated through evaluation of the squamous cell layer that lines the vagina in a test known as a maturation index.

The relationship between hormone cycles and the maturation of vaginal squamous cells were initially noted by Rameriz and then later by Papanicolaou in the 1920’s. Papanicolaou’s research focused on the hormonal cycles of the female genitalia, and the efficacy of exfoliative cytology in the detection of cervical cancer was an incidental finding. A Maturation Index (MI) is based on the assumption that the sex hormones estrogen, progesterone and androgens (testosterone) bring about maturation in squamous cells that can be detected by cytological examination. The higher the number of mature cells (those designated ‘superficial’ and ‘intermediate’, the higher the maturation index or estrogen effect in the body. This provides doctors with information regarding levels of estrogen and hormonal influence in their female patients.

An MI is a ratio obtained through performing a random count of three major cell types (parabasal cells, intermediate cells and superficial cells) that are shed from the squamous epithelium. The cell count is expressed as a percentage that reads as follows: MI= % parabasal cells, % intermediate cells, % superficial cells. Parabasal cells are the least mature cells having not been affected by estrogen or progesterone. Intermediate cells display mild maturation, having been affected by progesterone, and superficial cells display the most maturity, having been affected by estrogen. A patient’s MI can vary on a daily basis, and of course MIs vary from patient to patient. There are only two absolutes when it comes to cellular patterns in an MI: the first is that a predominance of parabasal cells indicates an absence of estrogen stimulation, and second is that a predominance of superficial cells indicates estrogen stimulation. Intermediate cells have little clinical usefulness. The maturation index is useful for the evaluation of therapies designed to treat vaginal hormonal symptoms.

The Maturation Index provides practitioners with a simply obtained (samples are taken during the course of obtaining a pap smear) sample that is easily analyzed to detect hormonal changes in the vagina that are age-appropriate or an early sign of possible hormonal related disease processes. The best samples for an MI should be taken with a gentle scrape along the lateral wall of the upper vagina at the level of the cervix. Cellular tissue from this area accurately reflects the hormonal status at the time of collection. Samples obtained must be free from signs of inflammation (white blood cells) and endocervical cells, both of which may falsely elevate the MI. MIs are useful for evaluating hormonal function, evaluating cellular composition of the surface layers of vaginal tissue which reflects the balance of estrogen and progesterones effects on this tissue, and diagnosing conditions that produce abnormal hormonal balance (pituitary gland dysfunction, ovarian dysfunction, and hormone secreting tumors). Additionally, MIs can detect the beginnings of endometrial cancer in menopausal women, and have been used to screen for other cancerous process such as vaginal adenosis and clear cell carcinoma in women who were exposed in utero to diethylstilbestrol (DES), a synthetic estrogen. The sensitivity of using a smear to determine a maturation index in the diagnosis of vaginal intraepithelial neoplasia was estimated to be at 83% percent in one recent study.

Taking the following table into account, practitioners can decide on a course of treatment for the patient that presents with clinical symptoms once this hormonal ‘cross check’ has been measured. The maturation index is most useful for detecting hormonal effects in menopausal and post-menopausal women, who may be experiencing symptoms with and without treatment.4 Additionally, practitioners may find the use of an MI in post-menopausal woman to be a good screening tool for as-of-yet undetected vaginal cancers. Cellular cytology is useful in this process, detecting cellular changes prior to organ dysfunction, when the disease is in an advanced state.

Various treatments for female hormonal health and normalization exist, from standard hormone replacement therapies (HRT) and dietary and botanical medicines. Botanical medicines such as phytoestrogens have been shown to increase the MI in women consuming soy-rich diets over a 6-month period.5 Because of these effects, soy and other phytoestrogens should be considered as part of a preventative intervention in treating menopausal symptoms related to estrogen deficiency. However, the use of the maturation index should be correlated with clinical/symptomatic findings in order to accurately treat the patient’s symptoms and take steps to prevent worsening of symptoms or disease processes.

Day 14 – OvulationMI = 0:40:60Indicates mostly estrogen stimulation.
Day 28 – PremenstrualMI = 0:70:30Indicates mostly progesterone stimulation.
MenopausalMI = 0:100:0Progesterone only, no estrogen.
AtrophicMI = 100:0:0No progesterone or estrogen.
ChildMI = 100:0:0No progesterone or estrogen.
PubertyMI = 0:90:10Mostly progesterone stimulation, minimal estrogen.
PregnancyMI = 0:100:0Progesterone only, no estrogen.
Post PartumMI = 90:10:0Minimal hormonal stimulation. Ovarian function returns in 6-8 weeks.

1. McEndree B. Clinical application of the vaginal maturation index. Nurse Pract. 1999 Sep;24(9):48, 51-2, 55-6.

2. Van der Laak JA, Schijf CP, Kerstens HM, Heijnen-Wijnen TH, de Wilde PC, Hanselaar GJ. Development and validation of a computerized cytomorphometric method to assess the maturation of vaginal epithelial cells. Cytometry. 1999 Mar 1;35(3):196-202.

3. Davila RM, Miranda MC. Vaginal intraepithelial neoplasia and the Pap smear. Acta Cytol. 2000 Mar-Apr;44(2):137-40.

4. Greendale GA, Zibecchi L, Petersen L, Ouslander JG, Kahn B, Ganz PA. Development and validation of a physical examination scale to assess vaginal atrophy and inflammation. Climacteric. 1999 Sep;2(3):197-204.

5. Chiechi LM, Putignano G, Guerra V, Schiavelli MP, Cisternino AM, Carriero C. The effect of a soy rich diet on the vaginal epithelium in postmenopause: a randomized double blind trial. Maturitas. 2003 Aug 20;45(4):241-6.