How does lh and fsh work

Subsequent development of this cohort during the follicular phase becomes dependent on continued stimulation by gonadotropins. Increasing FSH concentrations should surpass the threshold level to initiate the final gonadotropin-dependent phase of follicular growth [ Figure 2 ]. There is a secretion of increasing amounts of estradiol during this phase. The peripheral estradiol levels are increased with feedback inhibition of FSH secretion.

The maturing follicle inhibits FSH secretion leading to a fall in its levels below threshold, thus stopping less mature follicles from maturing.

Further, it has been shown that FSH threshold is not fixed for any given follicle, but depends on the developmental stage and varies over time. The follicle with the highest sensitivity will benefit most from increasing FSH levels and will subsequently gain dominance. The suggested reasons for the response of ovarian follicles to certain FSH level than to a specific dose are fluctuating levels of the endogenous production of gonadotropin,[ 16 ] and up-regulation of its receptors due to FSH administration.

Although FSH can induce follicular growth even without LH, there is evidence that the follicles may have developmental deficiencies like abnormally reduced estradiol production and lack of ability to luteinize and rupture, following hCG stimulus. Another possibility is that FSH stimulates the production of progesterone by driving cholesterol conversion into the steroid pathway.

LH stimulates the conversion of progesterone into androgens, which can be further aromatized to estrogens. The addition of LH may benefit the endometrium by decreasing the risk of a premature progesterone increase and therefore improve the likelihood of implantation and clinical pregnancy. The concept of the LH therapeutic window has been explained in brief in Figure 3.

Though studies support the use of r-hLH in addition to r-hFSH in GnRH antagonist protocols in ovarian follicular development, these studies are fewer in number. There is also no clear cut guideline regarding the optimum levels of serum LH and timing of its supplementation are fewer in number. This is an area that warrants further research. A recent meta-analysis of seven randomized controlled trials RCTs done by Hill et al.

Patients with unfavorable genotypes are reported to require higher doses of r-hFSH to overcome relative ovarian insensitivity. The FSHR gene contains two important single nucleotide polymorphisms SNPs in exon 10, which are in linkage disequilibrium and change two amino acids at positions and These patients when undergoing ART are characterized by higher basal FSH serum concentrations, higher administered amounts of FSH required and higher risks of hypo- or hyper-responses.

They had initially suggested this discovery as an immunological anomalous LH form. Various studies suggest four parameters of FSH administration management involved in the risk of multifollicular development: a the choice of the FSH starting dose,[ 34 , 35 ] b the duration of the starting, dose before stepping up or stepping down,[ 34 , 36 ] c the rate of increase in FSH dose at each increment[ 37 ] and d the reduction of the FSH dose once a follicle has been selected.

In an attempt to prevent the risks of overstimulation and multiple pregnancies, it is crucial to use a low starting dose of FSH,[ 37 ] and to use small increments in the daily dosage. LH is important in regulating steroidogenesis throughout follicular development; adequate LH is particularly important for oocyte maturation. Published literature on the beneficial effects of exogenous LH in patients with previous suboptimal response or low baseline serum LH concentrations is more extensive in long agonist protocols.

Many factors are linked to a decreased ovarian response and hence, it is difficult to identify poor responders. Although several tests have been suggested, none can indicate it accurately. Some putative biomarkers to identify poor responders include i LH concentrations either at baseline or day 6 midfollicular ii AMH levels and iii antral follicle count AFC.

Wong et al. Evidence indicates that r-hLH and r-hFSH co-administration in these patients may help in improving ongoing pregnancy rates in poor responders and women of advanced age.

An open-label randomized controlled study found that r-hLH is beneficial in improving the implantation rate in women aged years, but not so in those younger than 36 years of age. LH administration enhances follicular androgen production followed by its aromatization to estrogen. It also controls progesterone production by granulosa cells, which is also FSH dependent. Several studies correlated the occurrence of apoptosis in granulosa cells with the IVF outcome.

The incidence of apoptosis was lower in granulosa cells of follicles aspirated from patients who became pregnant after ivf cycle compared with granulosa cells of follicles aspirated from patients who are non-pregnant. Recently Gatta et al. Thus, LH supplementation seems appropriate for aged patients and poor responders where it restores the follicular and endometrial milieu and improves the cycle outcome. The detrimental impact of endocrinological disorder, which is linked to hyper-secretion of LH and ovulatory dysfunction, is attributed to increased LH levels.

Studies have found that such women are associated with poor fertilization, oocyte quality and embryo quality, which could be due to underlying mechanisms such as androgen excess induced by LH. However, contrary to previous belief, it was later demonstrated that hyper-insulinemia and not LH hyper-secretion plays a vital role in PCOS pathogenesis. LH supplementation is important in older and poor-responding patients because they usually receive higher FSH doses for COS, show higher progesterone levels at the end of stimulation and subsequently, their endometrium receptivity diminishes.

In , the European Study Group conducted the first randomized efficacy clinical study to investigate the safety and tolerability of r-hLH supplementation in hypogonadotropic hypogonadal women WHO group 1 anovulation.

The researchers also aimed to assess the minimal effective dose for this patient population. The results were showed that r-hLH helped in:.

Promoting dose-associated increase in the secretion of estradiol and androstenedione by r-hFSH-induced follicles. Enhancing ovarian sensitivity to FSH as observed in the number of patients who developed follicles following FSH administration. Based on the findings, the researchers recommended that 75 IU r-hLH is effective in most of the women by facilitating maximal endometrial growth and optimal follicular development, which is defined as:.

This might be due to excessive or inconsistent LH activity from the hCG component in hMG may affect ocyte maturation in the latter half of the ovarian stimulation cycle, giving rise to the differences in numbers of oocytes retrieved and success of pregnancy. Optimal follicle development with subsequent ovulation requires the complex interaction of FSH, LH and their complementary activities. Thus, ART outcome can be improved with optimization of FSH dose in various patient populations and supplementation of LH in various subgroups discussed above.

Biomarkers to ascertain women who are in need of exogenous LH need to be sought. With the increasing evidence of pharmacogenetic approaches, it is likely that the choice of ART regimen will be also guided by patient's genetic makeup. We suggest that before deciding on use of exogenous LH, it is crucial to identify patients who would benefit the most from LH supplementation and assess the cost-benefit ratio in the use of exogenous LH.

Further research is needed to arrive at a clear and uniform consensus on dosage, timing and patient population who would benefit the most with LH supplementation. The authors are grateful to acknowledge Knowledge Isotopes www. Conflict of Interest: This review article is the result of a series of advisory board meetings supported by Merck Specialties Private Limited.

National Center for Biotechnology Information , U. J Hum Reprod Sci. Endocrinology excl diabetes Gynaecology and urinary tract disorders female. Reproductive hormones: The right test, at the right time, for the right patient Understanding the physiology of reproductive hormones, recognising pathology and knowing what tests to order, when to order them and how to interpret the results can be daunting.

In this article What are the main reproductive hormones? When should reproductive hormones be investigated? References In this article. What are the main reproductive hormones?

Follicle stimulating hormone FSH and luteinising hormone LH Luteinising hormone LH and follicle stimulating hormone FSH are important pituitary hormones, required for reproductive processes in both males and females. Oestradiol Oestradiol is the principal oestrogen in females who are ovulating and the dominant ovarian hormone during the follicular first phase of the menstrual cycle.

Progesterone Progesterone is the dominant ovarian hormone secreted during the luteal second phase of the menstrual cycle. Prolactin In females, prolactin stimulates the breasts to produce milk, after oestrogen priming. Testosterone Testosterone is the primary androgen responsible for the development and maintenance of male sexual characteristics. First exclude pregnancy where appropriate. Secondary amenorrhoea or oligomenorrhoea First exclude pregnancy.

Add FSH only if fertility concerns. Tests dependent on suspected cause. Add oestradiol and hCG if gynaecomastia is suspected. Fertility in females with regular menstruation - - - May add day 21progesterone.

If irregular menstruation, investigate as per secondary amenorrhoea. Fertility in males - - - Following abnormal semen analysis. Precocious puberty Precocious early puberty is generally defined as the appearance of secondary sexual characteristics in girls aged under eight years or in boys aged under nine years.

Hyperprolactinaemia Stress, medicine use and hypothyroidism need to be considered as causes of hyperprolactinaemia. Investigating menopause Hormone testing is usually not necessary for diagnosing menopause or monitoring treatment. Investigating hypogonadism in males Delayed puberty The first sign of puberty in males is an increase in the size of the testes, which normally occurs around age 12 years. Gynaecomastia Gynecomastia is a benign enlargement of the breast tissue in males, which indicates an imbalance between free oestrogen and androgens.

Late-onset hypogonadism In an adult male with clinically significant signs and symptoms of hypogonadism e. Androgen resistance Oestradiol measurement is recommended in males with a finding of high serum testosterone and LH levels, along with features of undermasculinisation e. Investigating early pregnancy A random urine hCG test can be used in primary care to diagnose early pregnancy. References Editor: Kyle C. A handbook for the interpretation of laboratory tests.

Diagnostic Medlab; Faculty of Sexual and Reproductive Healthcare. Contraception for women aged over 40 years. Faculty of Sexual and Reproductive Healthcare; Available from: www. Kay V, Barratt C. Male obesity: impact on fertility. Br J Diab Vasc Dis — Androgen excess disorders in women. Second ed. Symptomatic patients with an early viable intrauterine pregnancy: HCG curves redefined. Obstet Gynecol ; 1 —5.

Prenatal Diag ;32 1 —9. SOGC clinical practice guidelines. Ultrasound evaluation of first trimester pregnancy complications. Int J Gynaecol Obstet ;93 1 — Human chorionic gonadotropin profile for women with ectopic pregnancy. Obstet Gynecol ; 3 — Hayden C, Balen A. Primary amenorrhoea: investigation and treatment. Ob Gynae Rep Med ;17 7 — Master-Hunter T, Heiman D. Amenorrhoea: evaluation and treatment.

Am Fam Physician ;73 8 — Revised consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril ;81 1 — Smellie WS. Best practice in primary care pathology: review 2. J Clin Pathol ;59 2 — McClure R. Endocrinology of male infertility. Contemporary endocrinology: office andrology. Patton P, Battaglia D Eds. Kamel RM. Management of the infertile couple: an evidence-based protocol. Reprod Biol Endocrinol ; Taylor A. ABC of sub-fertility: Making a diagnosis.

BMJ ; —7. Royal College of Obstetricians and Gynaecologists. Infertility: RCOG guidelines. Mayo Clinic. Home pregnancy tests: Can you trust the results? Comments There are currently no comments for this article. Make a comment:. Please login to make a comment. This article is 8 years and 9 months old. Social sharing. In this issue Best tests?

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Chronic pelvic pain in women Testosterone use in older males An update on the use of nitrofurantoin in patients with renal impairment. Inpractice Recertification programme ». South Link Health South Island general practice support ». The secretion of luteinising hormone from the anterior pituitary gland is regulated through a system called the hypothalamic-pituitary-gonadal axis. Gonadotrophin-releasing hormone is released from the hypothalamus and binds to receptors in the anterior pituitary gland to stimulate both the synthesis and release of luteinising hormone and follicle stimulating hormone.

The released luteinising hormone is carried in the bloodstream where it binds to receptors in the testes and ovaries to regulate their hormone secretions and the production of sperm or eggs. The release of hormones from the gonads can suppress the secretion of gonadotrophin-releasing hormone and, in turn, luteinising hormone from the anterior pituitary gland.

When levels of hormones from the gonads fall, the reverse happens and gonadtrophin-releasing hormone and hence luteinising hormone rise. This is known as negative feedback. In men, testosterone exerts this negative feedback and in women oestrogen and progesterone exert the same effect except at the midpoint in the menstrual cycle. At this point, high oestrogen secretions from the ovary stimulate a surge of luteinising hormone from the pituitary gland, which triggers ovulation. The fine tuning of luteinising hormone release is vital to maintaining fertility.

Because of this, compounds designed to mimic the actions of gonadotrophin-releasing hormone, luteinising hormone and follicle stimulating hormone are used to stimulate gonadal function in assisted conception techniques such as in vitro fertilisation IVF. Measuring the levels of luteinising hormone present in urine can be used to predict the timing of the luteinising hormone surge in women, and hence ovulation.

This is one of the methods employed in ovulation prediction kits used by couples wishing to conceive. Too much luteinising hormone can be an indication of infertility. Since the secretion of luteinising hormone is tightly controlled by the hypothalamic-pituitary-gonadal axis, high levels of luteinising hormone in the bloodstream can indicate decreased sex steroid production from the testes or ovaries for example, as in premature ovarian failure.

Polycystic ovary syndrome is a common condition in women associated with high levels of luteinising hormone and reduced fertility. In this condition, an imbalance between luteinising hormone and follicle stimulating hormone can stimulate inappropriate production of testosterone.