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Table 1 Kisspeptin and its analogs regulate LH secretion in women.

From: Advances in clinical applications of kisspeptin-GnRH pathway in female reproduction

Studies

Agonists

Participants

Treatment

Baseline LH (IU/L)

Max LH (IU/L) after treatment

(Dhillo et al. 2007) [50]

KP54

26-32 healthy women

sc bolus 0.2, 0.4, 0.8, 1.6, 3.2, and 6.4 nmol/kg in the follicular phase;

sc bolus 0.4 nmol/kg in each phase of the menstrual cycle (follicular, preovulatory, and luteal phase)

follicular: 4.2

preovulatory: 14.5

luteal: 3.6 in each phase

The highest increase: preovulatory phase

(Jayasena et al. 2011) [51]

KP10

35 healthy women

iv bolus 0.3, 1.0, 3.0, or 10 nmol/kg in follicular phase and preovulatory phase women

2.9

3.8/6.8

Increase only in preovulatory phase women

(Jayasena, Comninos, Veldhuis, et al. 2013) [52]

KP54

6 healthy women

sc bolus 0.15, 0.30, 0.60 nmol/kg

1.2-9.0

Increase: 2.3 in 0.60 nmol/kg

(Jayasena, Comninos, Nijher, et al. 2013) [53]

KP54

5 healthy women

twice-daily sc injections 6.4 nmol/kg during menstrual days 7-14

5.7

Increase: 8.6 on day 7

Increase: 12.7 on day 14

(Narayanaswamy et al. 2016) [54]

KP54

4 healthy women

sc infusion 0.1, 0.3 or 1.0 nmol/kg/h for 8 h

4.6

Around 5, 10, 10

(Skorupskaite et al. 2016) [55]

KP10

20 healthy women

iv infusion 4 μg/kg/h for 7 h

4.8-5.6

21.6

(Skorupskaite et al. 2018) [56]

KP10

Postmenopausal women (n=11)

iv bolus 0.3 μg/kg

Unclear

No increase

(Chan et al. 2012) [57]

KP10

10 women in early follicular phase, 3 in preovulatory phase, and 14 in midluteal phase

iv bolus 0.24 nmol/kg

follicular phase: 2.9

preovulatory phase: 34.7

midluteal phase: 3.4

follicular phase: 3.8

preovulatory phase: 61.3

midluteal phase: 7.1

(George, Anderson, and Millar 2012) [58]

KP10

10 women in early follicular phase, 6 post-menopausal, 4 with progestogen implants, 4 with COCP

iv bolus 0.3 μg/kg

follicular phase: 6.3, post-menopausal: 35.3, progestogen implants: 4.6, CPCP: 2.3

follicular phase: 9.4, post-menopausal: 44.7, progestogen implants: 7.5, CPCP: 3.7

(Jayasena, Abbara, Comninos, et al. 2014) [59]

KP54

53 women undergoing IVF (preovulatory phase)

sc bolus 1.6 nmol/kg, 3.2 nmol/kg, 6.4 nmol/kg, 12.8 nmol/kg

0.8, 1.4, 1.3, 1.3

6.6, 3.8, 7.9, 8.8

(Abbara et al. 2017) [60]

KP54

62 women at high risk of OHSS (preovulatory phase)

sc bolus 9.6 nmol/kg

second sc bolus 9.6 nmol/kg 10 h later

Around 2

Around 20

Around 50

Around 24

(Romero-Ruiz et al. 2019) [61]

KP54

12 women with PCOS

sc 9.6 nmol/kg twice daily for 21 days

10.8

7-day after completion of treatments: 13.4

(Skorupskaite et al. 2020) [62]

KP10

10 women with PCOS

iv infusion 4 μg/kg/h for 7 h

5.2

7.8

(Jayasena et al. 2009) [63]

KP54

10 women with HA

sc 6.4 nmol/kg twice daily for two weeks

2.6

24.0 at 4 h

Increase: 2.5 on day 14

(Jayasena et al. 2010) [64]

KP54

20 women with HA

sc 6.4 nmol/kg twice daily for two weeks

sc 6.4 nmol/kg twice weekly for eight weeks

2.5

1.8

23.3 at 6 h; 3.5 on day 14

1.9 after eight weeks

(Jayasena, Abbara, Veldhuis, et al. 2014) [65]

KP54

5 women with HA

iv infusion 1.00 nmol/kg/h for 8 h

1.3

15.4

(Millar et al. 2017) [66]

KP10

2 women with HA

iv infusion 1.5 μg/kg/h for 12 h

Patient 1: 5.3

Patient 2: 1.2

Patient 1: 25.4

Patient 2: 5.2

(Abbara et al. 2020) [67]

KP54

TAK-448

9 healthy women, 6 women with PCOS and 6 with HA

TAK-448 (doses 0.01 and 0.03 nmol/kg), KP54 (9.6 nmol/kg)

Healthy: 3.7

PCOS: 4.4

HA: 2.9

Amplitude of LH: similar after KP54 and MVT-602

Timing of peak LH: much later after MVT-602

  1. Abbreviations: IVF in vitro fertilization, OHSS Ovarian Hyperstimulation Syndrome, HA hypothalamic amenorrhea, PC prostate cancer, PCOS polycystic ovary syndrome, TSH thyroid-stimulating hormone, sc subcutaneous, iv intravenous, COCP combined oral contraceptive pills.