Hormones are body’s chemical messenger and they are vital in human body system. Hormonal imbalances can lead to a variety of disturbances and malfunctions in the human body. Likewise progesterone hormone plays a significant role in preterm birth and in infertility treated patients. All this cases are mainly related to the level of progesterone in human body, low level of aqueous progesterone can cause luteal phase defect by not causing favourable changes in the endometrium. Present article focuses on the role of progesterone for the luteal phase support as well as the thorough explanation regarding luteal phase defect.
Progesterone level is very important in women’s body as progesterone helps to carry out various complex process such as it brings favourable changes in the endometrium for successful development and maintenance of pregnancy, protection of fetal cells by suppressing immunity, suppressing cytokines, PGs, response to oxytocin, prevents formation of gap junction, it induces myometrial quiescence. Progesterone are also termed as nature’s natural immunosuppressant. Supplemental progesterone action is observed at cervix which during absence or presence of inflammation modulate gene expression in the cervix also blocks type 1 collagen degradation in cervix.
Progesterone is also called as progestin (female hormone). Progesterone used in women’s who are not pregnant but still they have not gone through menopause, in this case progesterone is used for restoring normal menstrual period. Also it is used in the cases to stop uterus bleeding which is caused due to low levels of progesterone.
Menstrual cycle
Menstrual cycle is the process of ovulation and menstruation in women’s. The process starts from the initial day of the menstruation when blood oozes out of the vagina. Average length of menstrual cycle is assumed to be of 28 days.
Menstrual phase (day 1-5)
During this phase shedding of inner lining of soft tissue as well as blood vessels takes place and which are eliminated as menstrual fluid from vagina. Experience of cramps are normal during this phase as normal quantity 10–80 ml of blood loss takes place along with the contraction of uterine for passage of menstrual fluid.
Follicular phase (day 1-13)
This phase also begins from the initial day but lasts long up to 13th day, pituitary gland secretes hormones which stimulates egg cells in the ovaries to grow, during the same duration maturity of the egg cell also takes place in a sac like structure called as follicle. After the maturation of egg cells development of endometrium that is lining of blood vessels and soft tissue at the uterus takes place.
Ovulation phase (day 14)
Eggs which are matured during the follicular phase are released with the secretion of hormones by pituitary gland. Fallopian tube imbibes the egg cells by the cilia of the fimbriae.
Luteal phase (day 15-28)
This phase lasts till 28th day. The egg cell remains in the fallopian tube for 24 hrs. Disintegration of egg cell takes place if a sperm cell does not impregnate the egg cell. After this the menstrual phase of next cycle begins.
Luteal phase defect
Luteal phase defect is an interruption in women’s menstrual cycle. The lining of the uterus doesn’t evolve properly during luteal phase defect which makes it difficult to remain pregnant or conceive. Abnormality in endometrial development and inadequate luteal phase are some of the synonyms for the luteal phase defect. When progesterone is released by ovaries, at this juncture it signals the inner lining of the uterus to develop endometrium. This defect occurs when the ovaries do not secrets progesterone or the inner lining of the uterus does not respond to the progesterone.
Luteal phase defect symptoms
It is associated with various symptoms such as less to frequent periods, miscarriage, difficulty in getting pregnant, spotting in between periods. This defect can cause or it is linked to different types of factors mainly obesity, PCOS, thyroid disorder, hyperprolactinemia, anorexia, endometriosis, excessive exercise.
Luteal phase diagnosis
As such a concrete diagnostic tool for LPD is not there but still symptoms such as cycle irregularity or premenstrual spotting is considered. This should be followed by early follicular phase diagnostic work-up. Other diagnostic work such as assay of progesterone-associated endometrial protein, analysis of decidual steroid receptors, or determination of decidual prolactin production can provide a good diagnosis. Sonographic criteria for LPD are rupture of follicle less than 17 mm, Improperly formed dominant follicle, lutenised unruptured follicle, absence of corpus luteum, lutein cyst formation, lack of endometrial echogenecity on 7th post ovulatory day.
Luteal phase support
Luteal phase support is the external supplementation of hormone and this support is required by the confirmed cases of luteal phase defect, unexplained infertility, advanced reproductive age, artificial reproductive techniques such as IUI/IVI/ICSI, hyper-prolactinaemia, all down regulated cycles, recurrent pregnancy loss, PCOS, women with heavy exercise and underweight. Luteal phase support consist of progesterone, human chorionic gonadotropins, estrogen, GnRH agonist. Luteal phase support should be luteomimatic in nature and not luteolytic whereas progesterone to a very large extent serve this property. Treatment should be carried with natural progesterone rather than synthetic progestins. Progesterone supplementation are mainly through three different routes oral, intramuscular and vaginal.
Oral route
Easy route and in micronized form, absorption capacity is of 10 per cent of the total. Low absorption capacity hence less effective. Shows the mechanism by first hepatic pass. Equipped with side effects such as sedation and hypnosis.
Intramuscular route
Progesterone in oil base formulation and it is much reliable and consistent in plasma level as it is rapidly absorbed in 2 to 8 hrs. Patients mostly shows incompliance to this route as it is difficult and painful.
Vaginal route
It reaches to the targeted organ in a more pleasant way with highest concentration in uterus and endometrium. Shows first uterine pass effect with least side effects. Patients shows compliance to this route as it can be done through self administration also.
Aqueous intramuscular progesterone
This medication is given daily via injection for around 6 to 8 days as per the prescription. It treats the following conditions such as abnormal uterine bleeding caused by imbalance of hormones medications, test detecting the presence of estrogen in the body medications, ovulation disorder, Ovarian dysfunction causing absence of menstrual periods.
A study was performed in 20 normal menstrual cycle samples which were collected and were analyzed. It was observed that during the follicular phase a progesterone mean concentration of 0.32 ± 0.25 (s) ng/ml plasma was found. After 4 to 6 days it was reached up to 10–20 ng/ml. From this duration the concentration fell rapidly to below 1 ng/ml as soon as the menstrual bleeding started.
Conclusion
Luteal phase defect therefore can lead to different health conditions and it is mainly caused due to low secretion of progesterone levels hence a supplementation of natural progesterone can be carried out, yet there is a scope to find a concrete diagnosis in near future which can diagnose the condition at a proper time and can prevent the ill effects caused due to luteal phase defect.
(Author is a Mumbai based pharmaceutical and healthcare consultant)